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US20110184046A1 - Compositions And Methods For Inhibiting Expression Of GSK-3 Genes - Google Patents

Compositions And Methods For Inhibiting Expression Of GSK-3 Genes Download PDF

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US20110184046A1
US20110184046A1 US13/003,740 US200913003740A US2011184046A1 US 20110184046 A1 US20110184046 A1 US 20110184046A1 US 200913003740 A US200913003740 A US 200913003740A US 2011184046 A1 US2011184046 A1 US 2011184046A1
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dsrna
sense
gsk
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Dinah Wen-Yee Sah
Dinah Sah
Gregory Hinkle
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Alnylam Pharmaceuticals Inc
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Definitions

  • the invention relates to a double-stranded ribonucleic acid (dsRNA) targeting Glycogen Synthase Kinase-3 alpha and/or beta (GSK-3 alpha and/or beta), and methods of using the dsRNA to inhibit expression of GSK-3. alpha and/or beta.
  • dsRNA double-stranded ribonucleic acid
  • Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine kinase. It functions as a key regulator of numerous signaling pathways. It phosphorylates and inactivates glycogen synthase, a key enzyme in glycogen metabolism. It has also been shown to be involved in the regulation of a diverse array of cellular functions, including protein synthesis, cell proliferation, cell differentiation, microtubule assembly/disassembly, and apoptosis. Two isoforms of GSK-3 have been reported in mammals: an approximately 51 kDa GSK-3 alpha form and an approximately 47 kDa GSK-3 beta form. These two isoforms exhibit about 98% homology in their kinase domains. Other regions share less homology: they share only about 36% identity in the last 76 C-terminal amino acid residues.
  • Double-stranded RNA molecules have been shown to block gene expression in a highly conserved regulatory mechanism known as RNA interference (RNAi).
  • RNAi RNA interference
  • WO 99/32619 (Fire et al.) disclosed the use of a dsRNA of at least 25 nucleotides in length to inhibit the expression of genes in C. elegans .
  • dsRNA has also been shown to degrade target RNA in other organisms, including plants (see, e.g., WO 99/53050, Waterhouse et al.; and WO 99/61631, Heifetz et al.), Drosophila (see, e.g., Yang, D., et al., Curr. Biol . (2000) 10:1191-1200), and mammals (see WO 00/44895, Limmer; and DE 101 00 586.5, Kreutzer et al.).
  • the invention provides compositions containing double-stranded ribonucleic acid (dsRNA) targeted to a GSK-3 gene and methods for inhibiting the expression of a GSK-3 gene in a cell or mammal.
  • the composition can inhibit GSK-3 alpha and/or GSK-3 beta.
  • a composition that inhibits both can do so, e.g., by including a dsRNA that targets both GSK-3 alpha and GSK-3 beta, or by including a first dsRNA that inhibits GSK-3 alpha and a second dsRNA that inhibits GSK-3 beta.
  • the composition can also include a dsRNA which inhibits both and a second which inhibits only one of the isoforms.
  • the invention also provides compositions and methods for treating manic depression (bipolar disorder).
  • compositions and methods for treating pathological conditions and diseases such as protozoan diseases (e.g., Plasmodium falciparum ), cancer (e.g., colorectal cancer), and circadian rhythm diseases (e.g., sleep disorders, jet lag, and shift work), are also provided.
  • pathological conditions and diseases such as protozoan diseases (e.g., Plasmodium falciparum ), cancer (e.g., colorectal cancer), and circadian rhythm diseases (e.g., sleep disorders, jet lag, and shift work), are also provided.
  • the dsRNAs described herein can also be used to regulate skeletal muscle growth, inflammatory responses, platelet function, apoptosis, and cellular responses to DNA damage.
  • the invention provides a double-stranded ribonucleic acid (dsRNA), having a sense strand and an antisense strand, the sense strand comprising a first sequence and the antisense strand comprising a second sequence, the second sequence comprising a region complementary to an mRNA encoding a GSK-3 gene, and wherein said region of complementarity is less than 30 nucleotides in length.
  • the second sequence includes a region complementary to the GSK-3 gene sequences NM — 019884, NM — 00103166, :NM — 002093, or NM — 019827.
  • the second sequence includes a region complementary to at least 15 nucleotides of a target sequence described herein, e.g., in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the second sequence can include a region complementary to a target sequence described in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the antisense strand of the dsRNA of the invention can include at least 15 nucleotides of one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the antisense strand includes one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the antisense strand consists of one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the sense strand can include at least 15 nucleotides of one of the sense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the sense strand can include or can consist of one of the sense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the dsRNA of the invention consists of one of the sense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 and the antisense strand consists of one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • Further embodiments include the duplexes disclosed herein, e.g., huGSKA-3, huGSKB-11, AD-18821, AD-18825, AD-18826, AD-18838, AD-18843, or AD-18844.
  • the dsRNA of the invention can include at least one modified nucleotide.
  • the modified nucleotides can be, e.g., a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, or a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.
  • the modified nucleotide(s) can be a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.
  • the dsRNA of the invention includes at least one 2′-O-methyl modified nucleotide and at least one nucleotide comprising a 5′-phosphorothioate group.
  • the region of complementarity of the dsRNA of the invention is less than 30 nucleotides, e.g., at least 15 nucleotides in length, or, e.g., between 19 and 21 nucleotides in length, or, e.g., 19 nucleotides in length.
  • dsRNA inhibits expression of GSK3 by more than 40%.
  • the dsRNA exhibits an IC50 of less than or equal to 10 nM in suppressing GSK3.
  • the dsRNA exhibits an IC50 of less than or equal to 1.0 nM in suppressing GSK3.
  • compositions for inhibiting expression of an GSK-3 gene comprising a dsRNA of the invention.
  • Methods of inhibiting GSK-3 expression in a cell are included in the invention.
  • the methods include (a) introducing into the cell the dsRNA of the invention; and (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a GSK-3 gene, thereby inhibiting expression of a GSK-3 gene in the cell.
  • Also included is a method of treating a disorder mediated by GSK-3 expression comprising administering to a human in need of such treatment a therapeutically effective amount of a dsRNA of the invention, including treatment of manic depression.
  • FIG. 1 is a graph illustrating the results of GSK3 ⁇ mRNA suppression in HT22 cells 24 hours after 37.5 nM siRNA transfection.
  • FIG. 2 is a graph illustrating the results of GSK3 ⁇ mRNA suppression in HT22 cells 24 hours after 37.5 nM siRNA transfection.
  • FIG. 3 is a graph illustrating the dose dependence of GSK3 ⁇ mRNA suppression after siRNA transfection of HT22 cells.
  • FIG. 4 is a graph illustrating the dose dependence of GSK3 ⁇ mRNA suppression after siRNA transfection of HT22 cells.
  • FIG. 5 is a western blot illustrating protein levels after siRNA transfection in HT22 cells.
  • FIG. 6 is a graph illustrating GSK3 ⁇ mRNA suppression in mouse nucleus accumbens after 14 day infusion of AD-18844 into the nucleus accumbens.
  • FIG. 7 is a graph illustrating GSK3 ⁇ mRNA suppression in mouse nucleus accumbens after 14 day infusion of AD-18826 into the nucleus accumbens.
  • the invention provides dsRNAs and methods of using the dsRNAs for inhibiting the expression of a GSK-3 gene in a cell or a mammal where the dsRNA targets a GSK-3 gene.
  • the invention also provides compositions and methods for treating pathological conditions and diseases, such as a metabolic disease or a cardiovascular disease, in a mammal caused by the expression of a GSK-3 gene.
  • dsRNA directs the sequence-specific degradation of mRNA through a process known as RNA interference (RNAi).
  • the dsRNAs of the compositions featured herein include an RNA strand (the antisense strand) having a region which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an mRNA transcript of a GSK-3 gene.
  • the use of these dsRNAs enables the targeted degradation of mRNAs of genes that are implicated in replication and or maintenance of cancer cells in mammals.
  • Very low dosages of GSK-3 dsRNAs in particular can specifically and efficiently mediate RNAi, resulting in significant inhibition of expression of the GSK-3 gene.
  • the methods and compositions of the invention containing the GSK-3 dsRNA are useful for treating pathological processes mediated by GSK-3 expression, e.g., manic depression, or other disorders described herein.
  • compositions containing dsRNAs to inhibit the expression of a GSK-3 gene, as well as compositions and methods for treating diseases and disorders caused by the expression of these genes, such as manic depression.
  • the pharmaceutical compositions featured in the invention include a dsRNA having an antisense strand comprising a region of complementarity which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an RNA transcript of a GSK-3 gene, together with a pharmaceutically acceptable carrier.
  • compositions featured in the invention also include a dsRNA having an antisense strand having a region of complementarity which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an RNA transcript of a GSK-3 gene.
  • compositions containing the GSK-3 dsRNA and a pharmaceutically acceptable carrier methods of using the compositions to inhibit expression of a GSK-3 gene, and methods of using the pharmaceutical compositions to treat diseases caused by expression of the GSK-3 gene.
  • G,” “C,” “A” and “U” each generally stand for a nucleotide that contains guanine, cytosine, adenine, and uracil as a base, respectively.
  • T and “dT” are used interchangeably herein and refer to a deoxyribonucleotide wherein the nucleobase is thymine, e.g., deoxyribothymine.
  • ribonucleotide or “nucleotide” or “deoxyribonucleotide” can also refer to a modified nucleotide, as further detailed below, or a surrogate replacement moiety.
  • guanine, cytosine, adenine, and uracil may be replaced by other moieties without substantially altering the base pairing properties of an oligonucleotide comprising a nucleotide bearing such replacement moiety.
  • a nucleotide comprising inosine as its base may base pair with nucleotides containing adenine, cytosine, or uracil.
  • nucleotides containing uracil, guanine, or adenine may be replaced in the nucleotide sequences of the invention by a nucleotide containing, for example, inosine. Sequences comprising such replacement moieties are embodiments of the invention.
  • GSK-3 refers to Glycogen Synthase Kinase-3, which is also known as DKFZp686D0638, GSK3, C86142, GSK-3beta, 7330414F15Rik, and 8430431H08Rik.
  • GSK-3 alpha sequence can be found as NCBI GeneID:2931 (human) and 606496 (mouse) and RefSeq ID number:NM — 019884 (human) and NM — 001031667 (mouse).
  • GSK-3 beta sequence can be found as NCBI GeneID:2932 (human) and 56637 (mouse) and RefSeq ID number:NM — 002093 (human) and NM — 019827 (mouse).
  • a dsRNA featured in the invention can target a specific GSK-3 isoform, e.g. GSK-3 alpha or GSK-3 beta, or a dsRNA of the invention can target both isoforms by binding to a common region of the mRNA transcript.
  • a dsRNA featured in the invention can target a specific GSK-3 beta isoform, e.g. GSK-3 beta 1 or GSK-3 beta 2, or a dsRNA of the invention can target both isoforms by binding to a common region of the mRNA transcript.
  • target sequence refers to a contiguous portion of the nucleotide sequence of an mRNA molecule formed during the transcription of a GSK-3 gene, including mRNA that is a product of RNA processing of a primary transcription product.
  • strand comprising a sequence refers to an oligonucleotide comprising a chain of nucleotides that is described by the sequence referred to using the standard nucleotide nomenclature.
  • the term “complementary,” when used to describe a first nucleotide sequence in relation to a second nucleotide sequence, refers to the ability of an oligonucleotide or polynucleotide comprising the first nucleotide sequence to hybridize and form a duplex structure under certain conditions with an oligonucleotide or polynucleotide comprising the second nucleotide sequence, as will be understood by the skilled person.
  • Such conditions can, for example, be stringent conditions, where stringent conditions may include: 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50° C. or 70° C. for 12-16 hours followed by washing.
  • sequences can be referred to as “fully complementary” with respect to each other herein.
  • first sequence is referred to as “substantially complementary” with respect to a second sequence herein
  • the two sequences can be fully complementary, or they may form one or more, but generally not more than 4, 3 or 2 mismatched base pairs upon hybridization, while retaining the ability to hybridize under the conditions most relevant to their ultimate application.
  • a dsRNA comprising one oligonucleotide 21 nucleotides in length and another oligonucleotide 23 nucleotides in length, wherein the longer oligonucleotide comprises a sequence of 21 nucleotides that is fully complementary to the shorter oligonucleotide, may yet be referred to as “fully complementary” for the purposes of the invention.
  • “Complementary” sequences may also include, or be formed entirely from, non-Watson-Crick base pairs and/or base pairs formed from non-natural and modified nucleotides, in as far as the above requirements with respect to their ability to hybridize are fulfilled.
  • Such non-Watson-Crick base pairs includes, but not limited to, G:U Wobble or Hoogstein base pairing.
  • a polynucleotide which is “substantially complementary to at least part of” a messenger RNA (mRNA) refers to a polynucleotide which is substantially complementary to a contiguous portion of the mRNA of interest (e.g., encoding a GSK-3) including a 5′ UTR, an open reading frame (ORF), or a 3′ UTR.
  • mRNA messenger RNA
  • a polynucleotide is complementary to at least a part of a GSK-3 mRNA if the sequence is substantially complementary to a non-interrupted portion of an mRNA encoding a GSK-3.
  • double-stranded RNA refers to a complex of ribonucleic acid molecules, having a duplex structure comprising two anti-parallel and substantially complementary, as defined above, nucleic acid strands.
  • dsRNA double-stranded RNA
  • the majority of nucleotides of each strand are ribonucleotides, but as described in detail herein, each or both strands can also include at least one non-ribonucleotide, e.g., a deoxyribonucleotide and/or a modified nucleotide.
  • dsRNA may include chemical modifications to ribonucleotides, including substantial modifications at multiple nucleotides and including all types of modifications disclosed herein or known in the art. Any such modifications, as used in an siRNA type molecule, are encompassed by “dsRNA” for the purposes of this specification and claims.
  • the two strands forming the duplex structure may be different portions of one larger RNA molecule, or they may be separate RNA molecules. Where the two strands are part of one larger molecule, and therefore are connected by an uninterrupted chain of nucleotides between the 3′-end of one strand and the 5′ end of the respective other strand forming the duplex structure, the connecting RNA chain is referred to as a “hairpin loop”.
  • the connecting structure is referred to as a “linker”.
  • the RNA strands may have the same or a different number of nucleotides. The maximum number of base pairs is the number of nucleotides in the shortest strand of the dsRNA minus any overhangs that are present in the duplex.
  • a dsRNA may comprise one or more nucleotide overhangs.
  • nucleotide overhang refers to the unpaired nucleotide or nucleotides that protrude from the duplex structure of a dsRNA when a 3′-end of one strand of the dsRNA extends beyond the 5′-end of the other strand, or vice versa.
  • “Blunt” or “blunt end” means that there are no unpaired nucleotides at that end of the dsRNA, i.e., no nucleotide overhang.
  • a “blunt ended” dsRNA is a dsRNA that is double-stranded over its entire length, i.e., no nucleotide overhang at either end of the molecule.
  • antisense strand refers to the strand of a dsRNA which includes a region that is substantially complementary to a target sequence.
  • region of complementarity refers to the region on the antisense strand that is substantially complementary to a sequence, for example a target sequence, as defined herein. Where the region of complementarity is not fully complementary to the target sequence, the mismatches are most tolerated in the terminal regions and, if present, are generally in a terminal region or regions, e.g., within 6, 5, 4, 3, or 2 nucleotides of the 5′ and/or 3′ terminus.
  • sense strand refers to the strand of a dsRNA that includes a region that is substantially complementary to a region of the antisense strand.
  • Introducing into a cell means facilitating uptake or absorption into the cell, as is understood by those skilled in the art. Absorption or uptake of dsRNA can occur through unaided diffusive or active cellular processes, or by auxiliary agents or devices. The meaning of this term is not limited to cells in vitro; a dsRNA may also be “introduced into a cell”, wherein the cell is part of a living organism. In such instance, introduction into the cell will include the delivery to the organism. For example, for in vivo delivery, dsRNA can be injected into a tissue site or administered systemically. In vitro introduction into a cell includes methods known in the art such as electroporation and lipofection.
  • the degree of inhibition is usually expressed in terms of
  • the degree of inhibition may be given in terms of a reduction of a parameter that is functionally linked to GSK-3 gene transcription, e.g., the amount of protein encoded by a GSK-3 gene which is secreted by a cell, or the number of cells displaying a certain phenotype, e.g., apoptosis.
  • GSK-3 gene silencing may be determined in any cell expressing the target, either constitutively or by genomic engineering, and by any appropriate assay.
  • the assay provided in the Examples below shall serve as such reference.
  • expression of a GSK-3 gene is suppressed by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by administration of the double-stranded oligonucleotide of the invention.
  • a GSK-3 gene is suppressed by at least about 60%, 70%, or 80% by administration of the double-stranded oligonucleotide of the invention.
  • a GSK-3 gene is suppressed by at least about 85%, 90%, or 95% by administration of the double-stranded oligonucleotide of the invention.
  • the terms “treat”, “treatment”, and the like refer to relief from or alleviation of pathological processes mediated by GSK-3 expression.
  • the terms “treat”, “treatment”, and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression of such condition, such as the slowing and progression of manic depression.
  • the phrases “therapeutically effective amount” and “prophylactically effective amount” refer to an amount that provides a therapeutic benefit in the treatment, prevention, or management of pathological processes mediated by GSK-3 expression or an overt symptom of pathological processes mediated by GSK-3 expression.
  • the specific amount that is therapeutically effective can be readily determined by ordinary medical practitioner, and may vary depending on factors known in the art, such as, e.g. the type of pathological processes mediated by GSK-3 expression, the patient's history and age, the stage of pathological processes mediated by GSK-3 expression, and the administration of other anti-pathological processes mediated by GSK-3 expression agents.
  • a “pharmaceutical composition” comprises a pharmacologically effective amount of a dsRNA and a pharmaceutically acceptable carrier.
  • pharmaceutically effective amount refers to that amount of an RNA effective to produce the intended pharmacological, therapeutic or preventive result. For example, if a given clinical treatment is considered effective when there is at least a 25% reduction in a measurable parameter associated with a disease or disorder, a therapeutically effective amount of a drug for the treatment of that disease or disorder is the amount necessary to effect at least a 25% reduction in that parameter.
  • pharmaceutically acceptable carrier refers to a carrier for administration of a therapeutic agent.
  • Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof.
  • the term specifically excludes cell culture medium.
  • pharmaceutically acceptable carriers include, but are not limited to pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives.
  • suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose, while corn starch and alginic acid are suitable disintegrating agents.
  • Binding agents may include starch and gelatin, while the lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract.
  • a “transformed cell” is a cell into which a vector has been introduced from which a dsRNA molecule may be expressed.
  • the invention provides double-stranded ribonucleic acid (dsRNA) molecules for inhibiting the expression of a GSK-3 gene in a cell or mammal, e.g., in a human having manic depression, or another disorder described herein, where the dsRNA includes an antisense strand having a region of complementarity which is complementary to at least a part of an mRNA formed in the expression of a GSK-3 gene, and where the region of complementarity is less than 30 nucleotides in length, and where said dsRNA, upon contact with a cell expressing a GSK-3 gene, inhibits the expression of a GSK-3 gene, e.g., by at least 30% as assayed by, for example, a PCR or branched DNA (bDNA) based method.
  • the dsRNA of the invention may further include one or more single-stranded nucleotide overhangs.
  • the dsRNA can be synthesized by standard methods known in the art as further discussed below, e.g., by use of an automated DNA synthesizer, such as are commercially available from, for example, Biosearch, Applied Biosystems, Inc.
  • the dsRNA includes two RNA strands that are sufficiently complementary to hybridize to form a duplex structure.
  • One strand of the dsRNA (the antisense strand) includes a region of complementarity that is substantially complementary, and generally fully complementary, to a target sequence, derived from the sequence of an mRNA formed during the expression of the GSK-3 gene
  • the other strand (the sense strand) includes a region that is complementary to the antisense strand, such that the two strands hybridize and form a duplex structure when combined under suitable conditions.
  • the duplex structure is between 15 and 30, or between 25 and 30, or between 18 and 25, or between 19 and 24, or between 19 and 21, or 19, 20, or 21 base pairs in length.
  • the duplex is 19 base pairs in length.
  • the duplex is 21 base pairs in length.
  • the duplex lengths can be identical or can differ.
  • the region of complementarity to the target sequence can be between 15 and 30, or between 25 and 30, or between 18 and 25, or between 19 and 24, or between 19 and 21, or 19, 20, or 21 base pairs in length. In one embodiment the region of complementarity is 19 nucleotides in length. In another embodiment the region of complementarity is 21 nucleotides in length. When two different siRNAs are used in combination, the region of complementarity can be identical or can differ.
  • Each strand of the dsRNA of invention is generally between 15 and 30, or between 18 and 25, or 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length. In other embodiments, each is strand is 25-30 nucleotides in length.
  • Each strand of the duplex can be the same length or of different lengths. When two different siRNAs are used in combination, the lengths of each strand of each siRNA can be identical or can differ.
  • the dsRNA of the invention can include one or more single-stranded overhang(s) of one or more nucleotides.
  • at least one end of the dsRNA has a single-stranded nucleotide overhang of 1 to 4, generally 1 or 2 nucleotides.
  • the antisense strand of the dsRNA has 1-10 nucleotides overhangs each at the 3′ end and the 5′ end over the sense strand.
  • the sense strand of the dsRNA has 1-10 nucleotides overhangs each at the 3′ end and the 5′ end over the antisense strand.
  • a dsRNAs having at least one nucleotide overhang can have unexpectedly superior inhibitory properties than the blunt-ended counterpart.
  • the presence of only one nucleotide overhang strengthens the interference activity of the dsRNA, without affecting its overall stability.
  • a dsRNA having only one overhang has proven particularly stable and effective in vivo, as well as in a variety of cells, cell culture mediums, blood, and serum.
  • the single-stranded overhang is located at the 3′-terminal end of the antisense strand or, alternatively, at the 3′-terminal end of the sense strand.
  • the dsRNA can also have a blunt end, generally located at the 5′-end of the antisense strand.
  • dsRNAs can have improved stability and inhibitory activity, thus allowing administration at low dosages, i.e., less than 5 mg/kg body weight of the recipient per day.
  • the antisense strand of the dsRNA has a nucleotide overhang at the 3′-end, and the 5′-end is blunt.
  • one or more of the nucleotides in the overhang is replaced with a nucleoside thiophosphate.
  • the targeted GSK-3 gene is the human GSK-3 gene. In another embodiment, the targeted GSK-3 gene is a mouse gene.
  • the sense strand of the dsRNA includes a sense sequence from Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7, and the antisense sequence includes an antisense sequence of Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • Alternative antisense agents that target elsewhere in the target sequence provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 can readily be determined using the target sequence and the flanking GSK-3 sequence.
  • dsRNAs comprising a duplex structure of between 20 and 23, but specifically 21, base pairs have been hailed as particularly effective in inducing RNA interference (Elbashir et al., EMBO 2001, 20:6877-6888). However, others have found that shorter or longer dsRNAs can be effective as well.
  • the dsRNAs of the invention can include at least one strand of a length of minimally 21 nt.
  • dsRNAs having one of the sequences of Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 minus only a few nucleotides on one or both ends may be similarly effective as compared to the dsRNAs described above.
  • dsRNAs having a partial sequence of at least 15, 16, 17, 18, 19, 20, or more contiguous nucleotides from one of the sequences of Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7, and differing in their ability to inhibit the expression of a GSK-3 gene in an assay as described herein below by not more than 5, 10, 15, 20, 25, or 30% inhibition from a dsRNA comprising the full sequence are contemplated by the invention.
  • Further dsRNAs that cleave within the target sequence provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 can readily be made using the GSK-3 sequence and the target sequence provided.
  • siRNA agents provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 identify a site in a GSK-3 mRNA that is susceptible to siRNA based cleavage.
  • the present invention further features siRNA agents that target within the sequence targeted by one of the agents of the present invention.
  • a second siRNA agent is said to target within the sequence of a first siRNA agent if the second siRNA agent cleaves the message anywhere within the mRNA that is complementary to the antisense strand of the first siRNA agent.
  • Such a second agent will generally consist of at least 15 contiguous nucleotides from one of the sequences provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 coupled to additional nucleotide sequences taken from the region contiguous to the selected sequence in the GSK-3 gene.
  • the last 15 nucleotides of SEQ ID NO:1 combined with the next 6 nucleotides from the target GSK-3 gene produces a single strand agent of 21 nucleotides that is based on one of the sequences provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • the dsRNA of the invention can contain one or more mismatches to the target sequence. In a preferred embodiment, the dsRNA of the invention contains no more than 3 mismatches. If the antisense strand of the dsRNA contains mismatches to a target sequence, it is preferable that the area of mismatch not be located in the center of the region of complementarity. If the antisense strand of the dsRNA contains mismatches to the target sequence, it is preferable that the mismatch be restricted to 5 nucleotides from either end, for example 5, 4, 3, 2, or 1 nucleotide from either the 5′ or 3′ end of the region of complementarity.
  • the dsRNA generally does not contain any mismatch within the central 13 nucleotides.
  • the methods described within the invention can be used to determine whether a dsRNA containing a mismatch to a target sequence is effective in inhibiting the expression of a GSK-3 gene. Consideration of the efficacy of dsRNAs with mismatches in inhibiting expression of a GSK-3 gene is important, especially if the particular region of complementarity in a GSK-3 gene is known to have polymorphic sequence variation within the population.
  • the sense and/or antisense sequences of the dsRNA molecules featured herein can have the primary sequence shown in the tables with or without the modifications shown in the tables. In other embodiments the dsRNA molecule can differ by not more than 1, 2 or 3 bases from that provided in the tables.
  • At least one end of the dsRNA has a single-stranded nucleotide overhang of 1 to 4, generally 1 or 2 nucleotides.
  • dsRNAs having at least one nucleotide overhang have superior inhibitory properties than their blunt-ended counterparts.
  • the presence of only one nucleotide overhang strengthens the interference activity of the dsRNA, without affecting its overall stability.
  • dsRNA having only one overhang has proven particularly stable and effective in vivo, as well as in a variety of cells, cell culture mediums, blood, and serum.
  • the single-stranded overhang is located at the 3′-terminal end of the antisense strand or, alternatively, at the 3′-terminal end of the sense strand.
  • the dsRNA may also have a blunt end, generally located at the 5′-end of the antisense strand.
  • Such dsRNAs have improved stability and inhibitory activity, thus allowing administration at low dosages, i.e., less than 5 mg/kg body weight of the recipient per day.
  • the antisense strand of the dsRNA has a nucleotide overhang at the 3′-end, and the 5′-end is blunt.
  • one or more of the nucleotides in the overhang is replaced with a nucleoside thiophosphate.
  • the dsRNA is chemically modified to enhance stability.
  • the nucleic acids of the invention may be synthesized and/or modified by methods well established in the art, such as those described in “Current protocols in nucleic acid chemistry”, Beaucage, S. L. et al. (Edrs.), John Wiley & Sons, Inc., New York, N.Y., USA, which is hereby incorporated herein by reference.
  • Specific examples of preferred dsRNA compounds useful in this invention include dsRNAs containing modified backbones or no natural internucleoside linkages.
  • dsRNAs having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone.
  • modified dsRNAs that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides.
  • Preferred modified dsRNA backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those) having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′.
  • Various salts, mixed salts and free acid forms are also included.
  • Preferred modified dsRNA backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatoms and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages.
  • morpholino linkages formed in part from the sugar portion of a nucleoside
  • siloxane backbones sulfide, sulfoxide and sulfone backbones
  • formacetyl and thioformacetyl backbones methylene formacetyl and thioformacetyl backbones
  • alkene containing backbones sulfamate backbones
  • sulfonate and sulfonamide backbones amide backbones; and others having mixed N, O, S and CH2 component parts.
  • both the sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups.
  • the base units are maintained for hybridization with an appropriate nucleic acid target compound.
  • an dsRNA mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA).
  • PNA peptide nucleic acid
  • the sugar backbone of an dsRNA is replaced with an amide containing backbone, in particular an aminoethylglycine backbone.
  • the nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative U.S.
  • PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al., Science, 1991, 254, 1497-1500.
  • Most preferred embodiments of the invention are dsRNAs with phosphorothioate backbones and oligonucleosides with heteroatom backbones, and in particular —CH 2 —NH—CH 2 —, —CH 2 —N(CH 3 )—O—CH 2 —[known as a methylene (methylimino) or MMI backbone], —CH 2 —O—N(CH 3 )—CH 2 —, —CH 2 —N(CH 3 )—N(CH 3 )—CH 2 — and —N(CH 3 )—CH 2 —CH 2 —[wherein the native phosphodiester backbone is represented as —O—P—O—CH 2 —] of the above-referenced U.S.
  • Modified dsRNAs may also contain one or more substituted sugar moieties.
  • Preferred dsRNAs comprise one of the following at the 2′ position: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C 1 to C 10 alkyl or C 2 to C 10 alkenyl and alkynyl.
  • dsRNAs comprise one of the following at the 2′ position: C 1 to C 10 lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH 3 , OCN, Cl, Br, CN, CF 3 , OCF 3 , SOCH 3 , SO 2 CH 3 , ONO 2 , NO 2 , N 3 , NH 2 , heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an dsRNA, or a group for improving the pharmacodynamic properties of an dsRNA, and other substituents having similar properties.
  • a preferred modification includes 2′-methoxyethoxy (2′-O—CH 2 CH 2 OCH 3 , also known as 2′-O-(2-methoxyethyl) or 2′-MOE) (Martin et al., Helv. Chim. Acta, 1995, 78, 486-504) i.e., an alkoxy-alkoxy group.
  • a further preferred modification includes 2′-dimethylaminooxyethoxy, i.e., a O(CH 2 ) 2 ON(CH 3 ) 2 group, also known as 2′-DMAOE, as described in examples herein below, and 2′-dimethylaminoethoxyethoxy (also known in the art as 2′-O-dimethylaminoethoxyethyl or 2′-DMAEOE), i.e., 2′—O—CH 2 —O—CH 2 —N(CH 2 ) 2 , also described in examples herein below.
  • modifications include 2′-methoxy (2′-OCH 3 ), 2′-aminopropoxy (2′-OCH 2 CH 2 CH 2 NH 2 ) and 2′-fluoro (2′-F). Similar modifications may also be made at other positions on the dsRNA, particularly the 3′ position of the sugar on the 3′ terminal nucleotide or in 2′-5′ linked dsRNAs and the 5′ position of 5′ terminal nucleotide. DsRNAs may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative U.S. patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat. Nos.
  • DsRNAs may also include nucleobase (often referred to in the art simply as “base”) modifications or substitutions.
  • base include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U).
  • Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl anal other 8-substituted adenines and guanines, 5-halo, particularly 5-bromo, 5-trifluoromethyl and other 5-substi
  • nucleobases include those disclosed in U.S. Pat. No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858-859, Kroschwitz, J. L, ed. John Wiley & Sons, 1990, these disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y S., Chapter 15, DsRNA Research and Applications, pages 289-302, Crooke, S. T. and Lebleu, B., Ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention.
  • 5-substituted pyrimidines include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine.
  • 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B., Eds., DsRNA Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions, even more particularly when combined with 2′- ⁇ -methoxyethyl sugar modifications.
  • dsRNAs of the invention involves chemically linking to the dsRNA one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the dsRNA.
  • moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acid. Sci. USA, 199, 86, 6553-6556), cholic acid (Manoharan et al., Biorg. Med. Chem. Let., 1994 4 1053-1060), a thioether, e.g., beryl-S-tritylthiol (Manoharan et al., Ann. N.Y. Acad.
  • Acids Res., 1990, 18, 3777-3783 a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyloxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937).
  • dsRNA compounds which are chimeric compounds. “Chimeric” dsRNA compounds or “chimeras,” in the context of this invention, are dsRNA compounds, particularly dsRNAs, which contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nucleotide in the case of an dsRNA compound.
  • dsRNAs typically contain at least one region wherein the dsRNA is modified so as to confer upon the dsRNA increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid.
  • An additional region of the dsRNA may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids.
  • RNase H is a cellular endonuclease which cleaves the RNA strand of an RNA:DNAduplex. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby greatly enhancing the efficiency of dsRNA inhibition of gene expression.
  • RNA target can be routinely detected by gel electrophoresis and, if necessary, associated nucleic acid hybridization techniques known in the art.
  • the dsRNA may be modified by a non-ligand group.
  • non-ligand molecules have been conjugated to dsRNAs in order to enhance the activity, cellular distribution or cellular uptake of the dsRNA, and procedures for performing such conjugations are available in the scientific literature.
  • Such non-ligand moieties have included lipid moieties, such as cholesterol (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86:6553), cholic acid (Manoharan et al., Bioorg. Med. Chem.
  • a thioether e.g., hexyl-5-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660:306; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3:2765), a thiocholesterol (Oberhauser et al., Nucl.
  • Acids Res., 1990, 18:3777 a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14:969), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36:3651), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264:229), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277:923).
  • Typical conjugation protocols involve the synthesis of dsRNAs bearing an aminolinker at one or more positions of the sequence. The amino group is then reacted with the molecule being conjugated using appropriate coupling or activating reagents. The conjugation reaction may be performed either with the dsRNA still bound to the solid support or following cleavage of the dsRNA in solution phase. Purification of the dsRNA conjugate by HPLC typically affords the pure conjugate.
  • GSK-3 specific dsRNA molecules that are expressed from transcription units inserted into DNA or RNA vectors (see, e.g., Couture, A, et al., TIG. (1996), 12:5-10; Skillern, A., et al., International PCT Publication No. WO 00/22113, Conrad, International PCT Publication No. WO 00/22114, and Conrad, U.S. Pat. No. 6,054,299).
  • These transgenes can be introduced as a linear construct, a circular plasmid, or a viral vector, which can be incorporated and inherited as a transgene integrated into the host genome.
  • the transgene can also be constructed to permit it to be inherited as an extrachromosomal plasmid (Gassmann, et al., Proc. Natl. Acad. Sci. USA (1995) 92:1292).
  • a dsRNA can be transcribed by promoters on two separate expression vectors and co-transfected into a target cell.
  • each individual strand of the dsRNA can be transcribed by promoters both of which are located on the same expression plasmid.
  • a dsRNA is expressed as an inverted repeat joined by a linker polynucleotide sequence such that the dsRNA has a stem and loop structure.
  • the recombinant dsRNA expression vectors are generally DNA plasmids or viral vectors.
  • dsRNA expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus (for a review, see Muzyczka, et al., Curr. Topics Micro. Immunol . (1992) 158:97-129)); adenovirus (see, for example, Berkner, et al., BioTechniques (1998) 6:616), Rosenfeld et al. (1991 , Science 252:431-434), and Rosenfeld et al. (1992), Cell 68:143-155)); or alphavirus as well as others known in the art.
  • adeno-associated virus for a review, see Muzyczka, et al., Curr. Topics Micro. Immunol . (1992) 158:97-129
  • adenovirus see, for example, Berkner, et al., BioTechniques
  • Retroviruses have been used to introduce a variety of genes into many different cell types, including epithelial cells, in vitro and/or in vivo (see, e.g., Eglitis, et al., Science (1985) 230:1395-1398; Danos and Mulligan, Proc. Natl. Acad. Sci. USA (1998) 85:6460-6464; Wilson et al., 1988 , Proc. Natl. Acad. Sci. USA 85:3014-3018; Armentano et al., 1990 , Proc. Natl. Acad. Sci . USA 87:61416145; Huber et al., 1991 , Proc. Natl. Acad. Sci.
  • Recombinant retroviral vectors capable of transducing and expressing genes inserted into the genome of a cell can be produced by transfecting the recombinant retroviral genome into suitable packaging cell lines such as PA317 and Psi-CRIP (Comette et al., 1991 , Human Gene Therapy 2:5-10; Cone et al., 1984 , Proc. Natl. Acad. Sci. USA 81:6349).
  • Recombinant adenoviral vectors can be used to infect a wide variety of cells and tissues in susceptible hosts (e.g., rat, hamster, dog, and chimpanzee) (Hsu et al., 1992 , J. Infectious Disease, 166:769), and also have the advantage of not requiring mitotically active cells for infection.
  • susceptible hosts e.g., rat, hamster, dog, and chimpanzee
  • Any viral vector capable of accepting the coding sequences for the dsRNA molecule(s) to be expressed can be used, for example vectors derived from adenovirus (AV); adeno-associated virus (AAV); retroviruses (e.g., lentiviruses (LV), Rhabdoviruses, murine leukemia virus); herpes virus, and the like.
  • AV adenovirus
  • AAV adeno-associated virus
  • retroviruses e.g., lentiviruses (LV), Rhabdoviruses, murine leukemia virus
  • herpes virus and the like.
  • the tropism of viral vectors can be modified by pseudotyping the vectors with envelope proteins or other surface antigens from other viruses, or by substituting different viral capsid proteins, as appropriate.
  • lentiviral vectors of the invention can be pseudotyped with surface proteins from vesicular stomatitis virus (VSV), rabies, Ebola, Mokola, and the like.
  • AAV vectors of the invention can be made to target different cells by engineering the vectors to express different capsid protein serotypes.
  • an AAV vector expressing a serotype 2 capsid on a serotype 2 genome is called AAV 2/2.
  • This serotype 2 capsid gene in the AAV 2/2 vector can be replaced by a serotype 5 capsid gene to produce an AAV 2/5 vector.
  • AAV vectors which express different capsid protein serotypes are within the skill in the art; see, e.g., Rabinowitz J E et al. (2002), J Virol 76:791-801, the entire disclosure of which is herein incorporated by reference.
  • Preferred viral vectors are those derived from AV and AAV.
  • the dsRNA of the invention is expressed as two separate, complementary single-stranded RNA molecules from a recombinant AAV vector having, for example, either the U6 or H1 RNA promoters, or the cytomegalovirus (CMV) promoter.
  • CMV cytomegalovirus
  • a suitable AV vector for expressing the dsRNA of the invention a method for constructing the recombinant AV vector, and a method for delivering the vector into target cells, are described in Xia H et al. (2002), Nat. Biotech. 20: 1006-1010.
  • Suitable AAV vectors for expressing the dsRNA of the invention, methods for constructing the recombinant AV vector, and methods for delivering the vectors into target cells are described in Samulski Ret al. (1987), J. Virol. 61: 3096-3101; Fisher K Jet al. (1996), J. Virol, 70: 520-532; Samulski R et al. (1989), J. Virol. 63: 3822-3826; U.S. Pat. No. 5,252,479; U.S. Pat. No. 5,139,941; International Patent Application No. WO 94/13788; and International Patent Application No. WO 93/24641, the entire disclosures of which are herein incorporated by reference.
  • the promoter driving dsRNA expression in either a DNA plasmid or viral vector of the invention may be a eukaryotic RNA polymerase I (e.g. ribosomal RNA promoter), RNA polymerase II (e.g. CMV early promoter or actin promoter or Ul snRNA promoter) or generally RNA polymerase III promoter (e.g. U6 snRNA or 7SK RNA promoter) or a prokaryotic promoter, for example the T7 promoter, provided the expression plasmid also encodes T7 RNA polymerase required for transcription from a T7 promoter.
  • RNA polymerase I e.g. ribosomal RNA promoter
  • RNA polymerase II e.g. CMV early promoter or actin promoter or Ul snRNA promoter
  • RNA polymerase III promoter e.g. U6 snRNA or 7SK RNA promoter
  • a prokaryotic promoter for example the T
  • the promoter can also direct transgene expression to the pancreas (see, e.g., the insulin regulatory sequence for pancreas (Bucchini et al., 1986 , Proc. Natl. Acad. Sci. USA 83:2511-2515)).
  • expression of the transgene can be precisely regulated, for example, by using an inducible regulatory sequence and expression systems such as a regulatory sequence that is sensitive to certain physiological regulators, e.g., circulating glucose levels, or hormones (Docherty et al., 1994 , FASEB J. 8:20-24).
  • inducible expression systems suitable for the control of transgene expression in cells or in mammals include regulation by ecdysone, by estrogen, progesterone, tetracycline, chemical inducers of dimerization, and isopropyl-beta-D1-thiogalactopyranoside (EPTG).
  • ETG isopropyl-beta-D1-thiogalactopyranoside
  • recombinant vectors capable of expressing dsRNA molecules are delivered as described below, and persist in target cells.
  • viral vectors can be used that provide for transient expression of dsRNA molecules.
  • Such vectors can be repeatedly administered as necessary. Once expressed, the dsRNAs bind to target RNA and modulate its function or expression. Delivery of dsRNA expressing vectors can be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that allows for introduction into a desired target cell.
  • the GSK-3 specific dsRNA molecules can also be inserted into vectors and used as gene therapy vectors for human patients.
  • Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see U.S. Pat. No. 5,328,470) or by stereotactic injection (see e.g., Chen et al. (1994) Proc. Natl. Acad. Sci. USA 91:3054-3057).
  • the pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can include a slow release matrix in which the gene delivery vehicle is imbedded.
  • the pharmaceutical preparation can include one or more cells which produce the gene delivery system.
  • compositions featured herein are administered in dosages sufficient to inhibit expression of a GSK-3 gene.
  • a suitable dose of dsRNA will be in the range of 0.01 to 200.0 milligrams per kilogram body weight of the recipient per day, generally in the range of 1 to 50 mg per kilogram body weight per day.
  • the dsRNA can be administered at 0.01 mg/kg, 0.05 mg/kg, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 3 mg/kg, 5.0 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, or 50 mg/kg per single dose.
  • the pharmaceutical composition may be administered once daily or the dsRNA may be administered as two, three, or more sub-doses at appropriate intervals throughout the day or even using continuous infusion or delivery through a controlled release formulation.
  • the dsRNA contained in each sub-dose must be correspondingly smaller in order to achieve the total daily dosage.
  • the dosage unit can also be compounded for delivery over several days, e.g., using a conventional sustained release formulation which provides sustained release of the dsRNA over a several day period. Sustained release formulations are well known in the art and are particularly useful for delivery of agents at a particular site, such as could be used with the agents of the present invention.
  • the dosage unit contains a corresponding multiple of the daily dose.
  • treatment of a subject with a therapeutically effective amount of a composition can include a single treatment or a series of treatments.
  • Estimates of effective dosages and in vivo half-lives for the individual dsRNAs encompassed by the invention can be made using conventional methodologies or on the basis of in vivo testing using an appropriate animal model, as described elsewhere herein.
  • the data obtained from cell culture assays and animal studies can be used in formulating a range of dosage for use in humans.
  • the dosage of compositions featured in the invention lies generally within a range of circulating concentrations that include the ED50 with little or no toxicity.
  • the dosage may vary within this range depending upon the dosage form employed and the route of administration utilized.
  • the therapeutically effective dose can be estimated initially from cell culture assays.
  • a dose may be formulated in animal models to achieve a circulating plasma concentration range of the compound or, when appropriate, of the polypeptide product of a target sequence (e.g., achieving a decreased concentration of the polypeptide) that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture.
  • a target sequence e.g., achieving a decreased concentration of the polypeptide
  • the IC50 i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms
  • levels in plasma may be measured, for example, by high performance liquid chromatography.
  • the dsRNAs featured in the invention can be administered in combination with other known agents effective in treatment of pathological processes mediated by target gene expression.
  • the administering physician can adjust the amount and timing of dsRNA administration on the basis of results observed using standard measures of efficacy known in the art or described herein.
  • the present invention also includes pharmaceutical compositions and formulations which include the dsRNA compounds of the invention.
  • the pharmaceutical compositions of the present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical, pulmonary, e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. In one embodiment, the pharmaceutical composition is administered intracranially, directly into the nucleus accumbens.
  • compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders.
  • Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.
  • Coated condoms, gloves and the like may also be useful.
  • Preferred topical formulations include those in which the dsRNAs of the invention are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants.
  • Preferred lipids and liposomes include neutral (e.g.
  • dioleoylphosphatidyl DOPE ethanolamine dimyristoylphosphatidyl choline DMPC, distearolyphosphatidyl choline) negative (e.g. dimyristoylphosphatidyl glycerol DMPG) and cationic (e.g. dioleoyltetramethylaminopropyl DOTAP and dioleoylphosphatidyl ethanolamine DOTMA).
  • DsRNAs of the invention may be encapsulated within liposomes or may form complexes thereto, in particular to cationic liposomes. Alternatively, dsRNAs may be complexed to lipids, in particular to cationic lipids.
  • Preferred fatty acids and esters include but are not limited arachidonic acid, oleic acid, eicosanoic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a C 1-10 alkyl ester (e.g. isopropylmyristate IPM), monoglyceride, diglyceride or pharmaceutically acceptable salt thereof.
  • Topical formulations are described in detail in U.S. patent application Ser. No. 09/315,298 filed on May 20, 1999 which is incorporated herein by reference in its entirety.
  • compositions and formulations for oral administration include powders or granules, microparticulates, nanoparticulates, suspensions or solutions in water or non-aqueous media, capsules, gel capsules, sachets, tablets or minitablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable.
  • Preferred oral formulations are those in which dsRNAs of the invention are administered in conjunction with one or more penetration enhancers surfactants and chelators.
  • Preferred surfactants include fatty acids and/or esters or salts thereof, bile acids and/or salts thereof.
  • Preferred bile acids/salts include chenodeoxycholic acid (CDCA) and ursodeoxychenodeoxycholic acid (UDCA), cholic acid, dehydrocholic acid, deoxycholic acid, glucholic acid, glycholic acid, glycodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, sodium tauro-24,25-dihydro-fusidate and sodium glycodihydrofusidate.
  • DCA chenodeoxycholic acid
  • UDCA ursodeoxychenodeoxycholic acid
  • cholic acid dehydrocholic acid
  • deoxycholic acid deoxycholic acid
  • glucholic acid glycholic acid
  • glycodeoxycholic acid taurocholic acid
  • taurodeoxycholic acid sodium tauro-24,25-dihydro-fusidate and sodium glycodihydrofusidate.
  • Preferred fatty acids include arachidonic acid, undecanoic acid, oleic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a monoglyceride, a diglyceride or a pharmaceutically acceptable salt thereof (e.g. sodium).
  • arachidonic acid arachidonic acid, undecanoic acid, oleic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyce
  • penetration enhancers for example, fatty acids/salts in combination with bile acids/salts.
  • a particularly preferred combination is the sodium salt of lauric acid, capric acid and UDCA.
  • Further penetration enhancers include polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether. DsRNAs of the invention may be delivered orally, in granular form including sprayed dried particles, or complexed to form micro or nanoparticles.
  • DsRNA complexing agents include poly-amino acids; polyimines; polyacrylates; polyalkylacrylates, polyoxethanes, polyalkylcyanoacrylates; cationized gelatins, albumins, starches, acrylates, polyethyleneglycols (PEG) and starches; polyalkylcyanoacrylates; DEAE-derivatized polyimines, pollulans, celluloses and starches.
  • Particularly preferred complexing agents include chitosan, N-trimethylchitosan, poly-L-lysine, polyhistidine, polyornithine, polyspermines, protamine, polyvinylpyridine, polythiodiethylaminomethylethylene P(TDAE), polyaminostyrene (e.g.
  • compositions and formulations for parenteral, intrathecal, intraventricular or intrahepatic administration may include sterile aqueous solutions which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients.
  • compositions of the present invention include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids. Particularly preferred are formulations that target the liver when treating hepatic disorders such as hepatic carcinoma.
  • the pharmaceutical formulations of the present invention may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.
  • compositions of the present invention may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, gel capsules, liquid syrups, soft gels, suppositories, and enemas.
  • the compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media.
  • Aqueous suspensions may further contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran.
  • the suspension may also contain stabilizers.
  • compositions of the present invention may be prepared and formulated as emulsions.
  • Emulsions are typically heterogenous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1 ⁇ m in diameter (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1, p.
  • Emulsions are often biphasic systems comprising two immiscible liquid phases intimately mixed and dispersed with each other.
  • emulsions may be of either the water-in-oil (w/o) or the oil-in-water (o/w) variety.
  • Emulsions may contain additional components in addition to the dispersed phases, and the active drug which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase.
  • compositions such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed.
  • Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) emulsions.
  • Such complex formulations often provide certain advantages that simple binary emulsions do not.
  • Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion.
  • a system of oil droplets enclosed in globules of water stabilized in an oily continuous phase provides an o/w/o emulsion.
  • Emulsions are characterized by little or no thermodynamic stability. Often, the dispersed or discontinuous phase of the emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity of the formulation. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incorporated into either phase of the emulsion.
  • Synthetic surfactants also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199).
  • Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion.
  • HLB hydrophile/lipophile balance
  • surfactants may be classified into different classes based on the nature of the hydrophilic group: nonionic, anionic, cationic and amphoteric (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285).
  • Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia.
  • Absorption bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations.
  • polar inorganic solids such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate.
  • non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives and antioxidants (Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).
  • Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed-phase droplets and by increasing the viscosity of the external phase.
  • polysaccharides for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth
  • cellulose derivatives for example, carboxymethylcellulose and carboxypropylcellulose
  • synthetic polymers for example, carbomers, cellulose ethers, and
  • Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.
  • free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite
  • antioxidant synergists such as citric acid, tartaric acid, and lecithin.
  • Emulsion formulations for oral delivery have been very widely used because of ease of formulation, as well as efficacy from an absorption and bioavailability standpoint (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p.
  • the compositions of dsRNAs and nucleic acids are formulated as microemulsions.
  • a microemulsion may be defined as a system of water, oil and amphiphile which is a single optically isotropic and thermodynamically stable liquid solution (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245).
  • microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain-length alcohol to form a transparent system.
  • microemulsions have also been described as thermodynamically stable, isotropically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in: Controlled Release of Drugs: Polymers and Aggregate Systems, Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 185-215).
  • Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte.
  • microemulsion is of the water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties of the oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 271).
  • microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously.
  • Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO 310 ), hexaglycerol pentaoleate (PO 500 ), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (SO750), decaglycerol decaoleate (DA0750), alone or in combination with cosurfactants.
  • ionic surfactants non-ionic surfactants
  • Brij 96 polyoxyethylene oleyl ethers
  • polyglycerol fatty acid esters tetraglycerol monolaurate (
  • the cosurfactant usually a short-chain alcohol such as ethanol, 1-propanol, and 1-butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because of the void space generated among surfactant molecules.
  • Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art.
  • the aqueous phase may typically be, but is not limited to, water, an aqueous solution of the drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol.
  • the oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and tri-glycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil.
  • materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and tri-glycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil.
  • Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absorption of drugs.
  • Lipid based microemulsions both o/w and w/o have been proposed to enhance the oral bioavailability of drugs, including peptides (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385-1390; Ritschel, Meth. Find. Exp. Clin. Pharmacol., 1993, 13, 205).
  • Microemulsions afford advantages of improved drug solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absorption due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385; Ho et al., J. Pharm. Sci., 1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or dsRNAs. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications.
  • microemulsion compositions and formulations of the present invention will facilitate the increased systemic absorption of dsRNAs and nucleic acids from the gastrointestinal tract, as well as improve the local cellular uptake of dsRNAs and nucleic acids.
  • Microemulsions of the present invention may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties of the formulation and to enhance the absorption of the dsRNAs and nucleic acids of the present invention.
  • Penetration enhancers used in the microemulsions of the present invention may be classified as belonging to one of five broad categories—surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of these classes has been discussed above.
  • liposome means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers.
  • Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Non-cationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo.
  • lipid vesicles In order to cross intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a liposome which is highly deformable and able to pass through such fine pores.
  • liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incorporate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245).
  • Important considerations in the preparation of liposome formulations are the lipid surface charge, vesicle size and the aqueous volume of the liposomes.
  • Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes and as the merging of the liposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act.
  • Liposomes present several advantages over other formulations. Such advantages include reduced side-effects related to high systemic absorption of the administered drug, increased accumulation of the administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin.
  • liposomes to deliver agents including high-molecular weight DNA into the skin.
  • Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting of the upper epidermis
  • Liposomes fall into two broad classes. Cationic liposomes are positively charged liposomes which interact with the negatively charged DNA molecules to form a stable complex. The positively charged DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al., Biochem. Biophys. Res. Commun., 1987, 147, 980-985).
  • Liposomes which are pH-sensitive or negatively-charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression of the exogenous gene was detected in the target cells (Zhou et al., Journal of Controlled Release, 1992, 19, 269-274).
  • liposomal composition includes phospholipids other than naturally-derived phosphatidylcholine.
  • Neutral liposome compositions can be formed from dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC).
  • Anionic liposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE).
  • DOPE dioleoyl phosphatidylethanolamine
  • Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC.
  • PC phosphatidylcholine
  • Another type is formed from mixtures of phospholipid and/or phosphatidylcholine and/or cholesterol.
  • Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol.
  • Non-ionic liposomal formulations comprising NovasomeTM I (glyceryl dilaurate/cholesterol/po-lyoxyethylene-10-stearyl ether) and NovasomeTM II (glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers of the skin (Hu et al. S.T.P.Pharma. Sci., 1994, 4, 6, 466).
  • Liposomes also include “sterically stabilized” liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incorporated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking such specialized lipids.
  • sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the liposome (A) comprises one or more glycolipids, such as monosialoganglioside G M1 , or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety.
  • PEG polyethylene glycol
  • Liposomes comprising (1) sphingomyelin and (2) the ganglioside G M1 or a galactocerebroside sulfate ester.
  • U.S. Pat. No. 5,543,152 discloses liposomes comprising sphingomyelin. Liposomes comprising 1,2-sn-dimyristoylphosphat-idylcholine are disclosed in WO 97/13499 (Lim et al).
  • liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art.
  • Sunamoto et al. (Bull. Chem. Soc. Jpn., 1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C 1215G , that contains a PEG moiety.
  • Illum et al. (FEBS Lett., 1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives.
  • Synthetic phospholipids modified by the attachment of carboxylic groups of polyalkylene glycols (e.g., PEG) are described by Sears (U.S.
  • Liposomes having covalently bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 B1 and WO 90/04384 to Fisher.
  • Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Pat. Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Pat. No. 5,213,804 and European Patent No. EP 0 496 813 B1).
  • Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Pat. No.
  • a number of liposomes comprising nucleic acids are known in the art.
  • WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes.
  • U.S. Pat. No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include a dsRNA.
  • U.S. Pat. No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes.
  • WO 97/04787 to Love et al. discloses liposomes comprising dsRNAs targeted to the raf gene.
  • Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets which are so highly deformable that they are easily able to penetrate through pores which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g., they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin.
  • HLB hydrophile/lipophile balance
  • Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general their HLB values range from 2 to about 18 depending on their structure.
  • Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters.
  • Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class.
  • the polyoxyethylene surfactants are the most popular members of the nonionic surfactant class.
  • Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates.
  • the most important members of the anionic surfactant class are the alkyl sulfates and the soaps.
  • Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class.
  • amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N-alkylbetaines and phosphatides.
  • a dsRNA featured in the invention is fully encapsulated in the lipid formulation to form a SPLP, pSPLP, SNALP, or other nucleic acid-lipid particle.
  • SNALP refers to a stable nucleic acid-lipid particle, including SPLP.
  • SPLP refers to a nucleic acid-lipid particle comprising plasmid DNA encapsulated within a lipid vesicle. SNALPs and SPLPs typically contain a cationic lipid, a non-cationic lipid, and a lipid that prevents aggregation of the particle (e.g., a PEG-lipid conjugate).
  • SPLPs include “pSPLP,” which include an encapsulated condensing agent-nucleic acid complex as set forth in PCT Publication No. WO 00/03683.
  • the particles of the present invention typically have a mean diameter of about 50 nm to about 150 nm, more typically about 60 nm to about 130 nm, more typically about 70 nm to about 110 nm, most typically about 70 to about 90 nm, and are substantially nontoxic.
  • nucleic acids when present in the nucleic acid-lipid particles of the present invention are resistant in aqueous solution to degradation with a nuclease.
  • Nucleic acid-lipid particles and their method of preparation are disclosed in, e.g., U.S. Pat. Nos. 5,976,567; 5,981,501; 6,534,484; 6,586,410; 6,815,432; and PCT Publication No. WO 96/40964.
  • the lipid to drug ratio (mass/mass ratio) (e.g., lipid to dsRNA ratio) will be in the range of from about 1:1 to about 50:1, from about 1:1 to about 25:1, from about 3:1 to about 15:1, from about 4:1 to about 10:1, from about 5:1 to about 9:1, or about 6:1 to about 9:1.
  • the cationic lipid may be, for example, N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP), N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA), N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA), 1,2-DiLinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA), 1,2-Dilinoleylcarbamoyloxy-3-dimethylamino
  • the compound 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane can be used to prepare lipid-siRNA nanoparticles. Synthesis of 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane is described in U.S. provisional patent application No. 61/107,998 filed on Oct. 23, 2008, which is herein incorporated by reference.
  • the lipid-siRNA particle includes 40% 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane: 10% DSPC: 40% Cholesterol: 10% PEG-C-DOMG (mole percent) with a particle size of 63.0 ⁇ 20 nm and a 0.027 siRNA/Lipid Ratio.
  • the non-cationic lipid may be an anionic lipid or a neutral lipid including, but not limited to, distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoyl-phosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoy
  • the conjugated lipid that inhibits aggregation of particles may be, for example, a polyethyleneglycol (PEG)-lipid including, without limitation, a PEG-diacylglycerol (DAG), a PEG-dialkyloxypropyl (DAA), a PEG-phospholipid, a PEG-ceramide (Cer), or a mixture thereof.
  • the PEG-DAA conjugate may be, for example, a PEG-dilauryloxypropyl (Ci 2 ), a PEG-dimyristyloxypropyl (Ci 4 ), a PEG-dipalmityloxypropyl (Ci 6 ), or a PEG-distearyloxypropyl (C] 8 ).
  • the conjugated lipid that prevents aggregation of particles may be from 0 mol % to about 20 mol % or about 2 mol % of the total lipid present in the particle.
  • the nucleic acid-lipid particle further includes cholesterol at, e.g., about 10 mol % to about 60 mol % or about 48 mol % of the total lipid present in the particle.
  • the lipidoid ND98.4HCl (MW 1487) (Formula I), Cholesterol (Sigma-Aldrich), and PEG-Ceramide C16 (Avanti Polar Lipids) can be used to prepare lipid-siRNA nanoparticles (i.e., LNP01 particles).
  • Stock solutions of each in ethanol can be prepared as follows: ND98, 133 mg/ml; Cholesterol, 25 mg/ml, PEG-Ceramide C16, 100 mg/ml.
  • the ND98, Cholesterol, and PEG-Ceramide C16 stock solutions can then be combined in a, e.g., 42:48:10 molar ratio.
  • the combined lipid solution can be mixed with aqueous siRNA (e.g., in sodium acetate pH 5) such that the final ethanol concentration is about 35-45% and the final sodium acetate concentration is about 100-300 mM.
  • aqueous siRNA e.g., in sodium acetate pH 5
  • Lipid-siRNA nanoparticles typically form spontaneously upon mixing.
  • the resultant nanoparticle mixture can be extruded through a polycarbonate membrane (e.g., 100 nm cut-off) using, for example, a thermobarrel extruder, such as Lipex Extruder (Northern Lipids, Inc). In some cases, the extrusion step can be omitted.
  • Ethanol removal and simultaneous buffer exchange can be accomplished by, for example, dialysis or tangential flow filtration.
  • Buffer can be exchanged with, for example, phosphate buffered saline (PBS) at about pH 7, e.g., about pH 6.9, about pH 7.0, about pH 7.1, about pH 7.2, about pH 7.3, or about pH 7.4.
  • PBS phosphate buffered saline
  • LNP01 formulations are described, e.g., in International Application Publication No. WO 2008/042973, which is hereby incorporated by reference.
  • the lipid-dsRNA particle can comprise a cationic lipid, a neutral lipid, a steroid, and optionally a lipid that prevents aggregation of the particle.
  • the relative percentages of these constitutents can vary depending on the type of lipids used.
  • the cationic lipid comprises from about 20 mol % to about 70 mol % or about 40 mol % to about 60 mol % of the total lipid present in the particle; neutral lipids comprise from about 5 mol % to about 90 mol %, about 10 mol %, or about 58 mol % if cholesterol is included, of the total lipid present in the particle; the steroid (typically cholesterol) can comprise from about 10 mol % to about 60 mol % or about 48 mol % of the total lipid present in the particle; finally, the lipid that prevents aggregation of the particle, typically a conjugated lipid (e.g., a PEG-conjugated lipid) can comprise from 0 mol % to about 20 mol % or about 2 mol % of the total lipid present in the particle.
  • a conjugated lipid e.g., a PEG-conjugated lipid
  • the lipid-dsRNA particle includes 40 mol % 2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane, 10 mol % 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 40 mol % Cholesterol, 10 mol % PEG-C-DOMG with a particle size of 63.0 ⁇ 20 nm and a 0.027 dsRNA/Lipid Ratio.
  • DSPC 1,2-distearoyl-sn-glycero-3-phosphocholine
  • the lipid-dsRNA particle includes 40 mol % 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 10 mol % 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 2 mol % 3-N—[(qmethoxypoly(ethylene glycol)2000)carbamoyl]-1,2-dimyristyloxy-propylamine (PEG-C-DMA), and 48 mol % cholesterol.
  • DMA 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane
  • DSPC 1,2-distearoyl-sn-glycero-3-phosphocholine
  • PEG-C-DMA 1,2-distearoyl-sn-glycero-3-phosphocholine
  • PEG-C-DMA 1,2-distearoyl-sn-glycero-3-phosphocholine
  • the lipid-dsRNA particle includes 57.1 mol % 1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLinDMA), 7.1 mol % DPPC, 34.4 mol % Cholesterol, 1.4 mol % PEG-cDMA.
  • DLinDMA 1,2-Dilinolenyloxy-N,N-dimethylaminopropane
  • DPPC 7.1 mol % DPPC
  • Cholesterol 1.4 mol % PEG-cDMA.
  • the lipid-dsRNA particle includes 48 mol % cholesterol, 20 mol % of the neutral lipid 1,2-distearoyl-sn-glycero-3-phosphocholine, 2 mol % of PEG-cDMA (3-N-[(methoxy poly(ethylene glycol)2000)carbamoyl]-1,2-dimyrestyloxypropylamine), and 30 mol % of the cationic lipid DLinDMA (1,2-dilinoleyloxy-3-(N,N-dimethyl)aminopropane).
  • the lipid-dsRNA particle includes 48 mol % cholesterol, 20 mol % of the neutral lipid 1,2-distearoyl-sn-glycero-3-phosphocholine, 2 mol % of PEG-cDMA (3-N-[(methoxy poly(ethylene glycol)2000)carbamoyl]-1,2-dimyrestyloxypropylamine), and 30 mol % of the cationic lipid 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane.
  • lipid-siRNA formulations are as follows:
  • Formulations prepared by either the in-line mixing or extrusion-free method can be characterized in similar manners.
  • formulations are typically characterized by visual inspection. They should be whitish translucent solutions free from aggregates or sediment. Particle size and particle size distribution of lipid-nanoparticles can be measured by light scattering using, for example, a Malvern Zetasizer Nano ZS (Malvern, USA). Particles should be about 20-300 nm, such as 40-100 nm in size. The particle size distribution should be unimodal.
  • the total siRNA concentration in the formulation, as well as the entrapped fraction is estimated using a dye exclusion assay.
  • a sample of the formulated siRNA can be incubated with an RNA-binding dye, such as Ribogreen (Molecular Probes) in the presence or absence of a formulation disrupting surfactant, e.g., 0.5% Triton-X100.
  • a formulation disrupting surfactant e.g. 0.5% Triton-X100.
  • the total siRNA in the formulation can be determined by the signal from the sample containing the surfactant, relative to a standard curve.
  • the entrapped fraction is determined by subtracting the “free” siRNA content (as measured by the signal in the absence of surfactant) from the total siRNA content. Percent entrapped siRNA is typically >85%.
  • the particle size is at least 30 nm, at least 40 nm, at least 50 nm, at least 60 nm, at least 70 nm, at least 80 nm, at least 90 nm, at least 100 nm, at least 110 nm, and at least 120 nm.
  • the suitable range is typically about at least 50 nm to about at least 110 nm, about at least 60 nm to about at least 100 nm, or about at least 80 nm to about at least 90 nm.
  • the present invention employs various penetration enhancers to effect the efficient delivery of nucleic acids, particularly dsRNAs, to the skin of animals.
  • nucleic acids particularly dsRNAs
  • Most drugs are present in solution in both ionized and nonionized forms. However, usually only lipid soluble or lipophilic drugs readily cross cell membranes. It has been discovered that even non-lipophilic drugs may cross cell membranes if the membrane to be crossed is treated with a penetration enhancer. In addition to aiding the diffusion of non-lipophilic drugs across cell membranes, penetration enhancers also enhance the permeability of lipophilic drugs.
  • Penetration enhancers may be classified as belonging to one of five broad categories, i.e., surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of the above mentioned classes of penetration enhancers are described below in greater detail.
  • surfactants are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between the aqueous solution and another liquid, with the result that absorption of dsRNAs through the mucosa is enhanced.
  • these penetration enhancers include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92); and perfluorochemical emulsions, such as FC-43. Takahashi et al., J. Pharm. Pharmacol., 1988, 40, 252).
  • Fatty acids Various fatty acids and their derivatives which act as penetration enhancers include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (1-monooleoyl-rac-glycerol), dilaurin, caprylic acid, arachidonic acid, glycerol 1-monocaprate, 1-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines, C.sub.1-10 alkyl esters thereof (e.g., methyl, isopropyl and t-butyl), and mono- and di-glycerides thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (Le
  • Bile salts The physiological role of bile includes the facilitation of dispersion and absorption of lipids and fat-soluble vitamins (Brunton, Chapter 38 in: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al. Eds., McGraw-Hill, New York, 1996, pp. 934-935).
  • bile salts includes any of the naturally occurring components of bile as well as any of their synthetic derivatives.
  • the bile salts of the invention include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholic acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate and polyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Swinyard, Chapter 39 In: Remington's Pharmaceutical Sciences,
  • Chelating agents can be defined as compounds that remove metallic ions from solution by forming complexes therewith, with the result that absorption of dsRNAs through the mucosa is enhanced.
  • chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett, J. Chromatogr., 1993, 618, 315-339).
  • Chelating agents of the invention include but are not limited to disodium ethylenediaminetetraacetate (EDTA), citric acid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of beta-diketones (enamines) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Buur et al., J. Control Rel., 1990, 14, 43-51).
  • EDTA disodium ethylenediaminetetraacetate
  • citric acid e.g., citric acid
  • salicylates e.g., sodium salicylate, 5-methoxysalicylate and homovanilate
  • N-acyl derivatives of collagen e.g., laureth-9 and N-amino acyl derivatives
  • Non-chelating non-surfactants As used herein, non-chelating non-surfactant penetration enhancing compounds can be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absorption of dsRNAs through the alimentary mucosa (Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33).
  • This class of penetration enhancers include, for example, unsaturated cyclic ureas, 1-alkyl- and 1-alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and non-steroidal anti-inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al., J. Pharm. Pharmacol., 1987, 39, 621-626).
  • Agents that enhance uptake of dsRNAs at the cellular level may also be added to the pharmaceutical and other compositions of the present invention.
  • cationic lipids such as lipofectin (Junichi et al, U.S. Pat. No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), are also known to enhance the cellular uptake of dsRNAs.
  • agents may be utilized to enhance the penetration of the administered nucleic acids, including glycols such as ethylene glycol and propylene glycol, pyrrols such as 2-pyrrol, azones, and terpenes such as limonene and menthone.
  • glycols such as ethylene glycol and propylene glycol
  • pyrrols such as 2-pyrrol
  • azones such as 2-pyrrol
  • terpenes such as limonene and menthone.
  • compositions of the present invention also incorporate carrier compounds in the formulation.
  • carrier compound or “carrier” can refer to a nucleic acid, or analog thereof, which is inert (i.e., does not possess biological activity per se) but is recognized as a nucleic acid by in vivo processes that reduce the bioavailability of a nucleic acid having biological activity by, for example, degrading the biologically active nucleic acid or promoting its removal from circulation.
  • a nucleic acid and a carrier compound can result in a substantial reduction of the amount of nucleic acid recovered in the liver, kidney or other extracirculatory reservoirs, presumably due to competition between the carrier compound and the nucleic acid for a common receptor.
  • the recovery of a partially phosphorothioate dsRNA in hepatic tissue can be reduced when it is coadministered with polyinosinic acid, dextran sulfate, polycytidic acid or 4-acetamido-4′ isothiocyano-stilbene-2,2′-disulfonic acid (Miyao et al., DsRNA Res. Dev., 1995, 5, 115-121; Takakura et al., DsRNA & Nucl. Acid Drug Dev., 1996, 6, 177-183.
  • a “pharmaceutical carrier” or “excipient” is a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal.
  • the excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a nucleic acid and the other components of a given pharmaceutical composition.
  • Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); and wetting agents (e.g., sodium lauryl sulphate, etc).
  • binding agents e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropy
  • compositions of the present invention can also be used to formulate the compositions of the present invention.
  • suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.
  • Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions of the nucleic acids in liquid or solid oil bases.
  • the solutions may also contain buffers, diluents and other suitable additives.
  • Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can be used.
  • Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.
  • compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels.
  • the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers.
  • additional materials useful in physically formulating various dosage forms of the compositions of the present invention such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers.
  • such materials when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention.
  • the formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation.
  • auxiliary agents e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation.
  • Aqueous suspensions may contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran.
  • the suspension may also contain stabilizers.
  • compositions containing (a) one or more antisense compounds and (b) one or more other chemotherapeutic agents which function by a non-antisense mechanism.
  • chemotherapeutic agents include but are not limited to daunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards
  • chemotherapeutic agents may be used individually (e.g., 5-FU and oligonucleotide), sequentially (e.g., 5-FU and oligonucleotide for a period of time followed by MTX and oligonucleotide), or in combination with one or more other such chemotherapeutic agents (e.g., 5-FU, MTX and oligonucleotide, or 5-FU, radiotherapy and oligonucleotide).
  • 5-FU and oligonucleotide e.g., 5-FU and oligonucleotide
  • sequentially e.g., 5-FU and oligonucleotide for a period of time followed by MTX and oligonucleotide
  • one or more other such chemotherapeutic agents e.g., 5-FU, MTX and oligonucleotide, or 5-FU, radiotherapy and oligonucleotide.
  • Anti-inflammatory drugs including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, may also be combined in compositions of the invention. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively). Other non-antisense chemotherapeutic agents are also within the scope of this invention. Two or more combined compounds may be used together or sequentially.
  • Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population).
  • the dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50.
  • Compounds which exhibit high therapeutic indices are preferred.
  • the data obtained from cell culture assays and animal studies can be used in formulation a range of dosage for use in humans.
  • the dosage of compositions of the invention lies generally within a range of circulating concentrations that include the ED50 with little or no toxicity.
  • the dosage may vary within this range depending upon the dosage form employed and the route of administration utilized.
  • the therapeutically effective dose can be estimated initially from cell culture assays.
  • a dose may be formulated in animal models to achieve a circulating plasma concentration range of the compound or, when appropriate, of the polypeptide product of a target sequence (e.g., achieving a decreased concentration of the polypeptide) that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture.
  • a target sequence e.g., achieving a decreased concentration of the polypeptide
  • the IC50 i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms
  • levels in plasma may be measured, for example, by high performance liquid chromatography.
  • the dsRNAs featured in the invention can be administered in combination with other known agents effective in treatment of pathological processes mediated by GSK-3 expression.
  • the administering physician can adjust the amount and timing of dsRNA administration on the basis of results observed using standard measures of efficacy known in the art or described herein.
  • the invention relates in particular to the use of a dsRNA targeting GSK-3 and compositions containing at least one such dsRNA, for the treatment of a GSK-3-mediated disorder or disease.
  • a dsRNA targeting a GSK-3 gene can be useful for the treatment of manic depression.
  • a metabolic disease such as metabolic disorders (e.g., Type I or Type II diabetes or metabolic syndrome) and nervous system disorders, (e.g., CNS or nuerogenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, Huntington's Disease, prion diseases (e.g., transmissible spongiform encephalopathies), stroke and schizophrenia).
  • CNS or nuerogenerative disorders e.g., Alzheimer's disease, Parkinson's disease, Huntington's Disease, prion diseases (e.g., transmissible spongiform encephalopathies), stroke and schizophrenia.
  • pathological conditions and diseases such as protozoan diseases (e.g., Plasmodium falciparum ), cancer (e.g., colorectal cancer), and circadian rhythm diseases (e.g., sleep disorders, jet lag, and shift work), and are also provided.
  • the dsRNAs described here can also be used to regulate skeletal muscle growth, inflammatory responses, platelet function, a
  • “Metabolic syndrome” is characterized by a group of metabolic risk factors including: abdominal obesity (excessive fat tissue in and around the abdomen), atherogenic dyslipidemia (blood fat disorders (including high triglycerides, low HDL cholesterol and high LDL cholesterol) that foster plaque build-up in artery walls), elevated blood pressure, insulin resistance or glucose intolerance (due to the body's inability to properly use insulin or blood sugar), a prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor-1 in the blood), and a proinflammatory state (e.g., elevated C-reactive protein in the blood).
  • abdominal obesity excessive fat tissue in and around the abdomen
  • atherogenic dyslipidemia blood fat disorders (including high triglycerides, low HDL cholesterol and high LDL cholesterol) that foster plaque build-up in artery walls)
  • elevated blood pressure including high triglycerides, low HDL cholesterol and high LDL cholesterol
  • insulin resistance or glucose intolerance due to the body's inability to
  • dsRNA targeting GSK-3 include obesity and insulin resistance.
  • a dsRNA targeting GSK-3 can be also be useful for the treatment of cancer, such as a colorectal cancer.
  • a composition containing a dsRNA targeting GSK-3 may also be used to treat other tumors and cancers, such as breast cancer, lung cancer, head and neck cancer, brain cancer, abdominal cancer, colon cancer, colorectal cancer, esophagus cancer, gastrointestinal cancer, glioma, tongue cancer, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, Wilm's tumor, multiple myeloma and for the treatment of skin cancer, like melanoma, for the treatment of lymphomas and blood cancer.
  • tumors and cancers such as breast cancer, lung cancer, head and neck cancer, brain cancer, abdominal cancer, colon cancer, colorectal cancer, esophagus cancer, gastrointestinal cancer, glioma, tongue cancer, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, Wilm's tumor, multiple myeloma and for
  • a composition according to the invention or a pharmaceutical composition prepared therefrom can enhance the quality of life.
  • the invention further relates to the use of a dsRNA or a pharmaceutical composition thereof, e.g., for treating manic depression or another disorder described herein, in combination with other pharmaceuticals and/or other therapeutic methods, e.g., with known pharmaceuticals and/or known therapeutic methods, such as, for example, those which are currently employed for treating these disorders.
  • the patient in the treatment of manic depression, can also be treated with one or more other therapeutic modalities, e.g., lithium salts, anticonvulsant mood stabilizers, antipsychotics, and other adjunctive treatments described herein.
  • the patient is also treated with lithium salts.
  • Lithium salts have been used as a first-line treatment for bipolar disorder. Common lithium salts are lithium carbonate and (probably less commonly) lithium citrate. Lithium orotate is used as an alternative treatment to lithium carbonate by some individuals with bipolar disorder.
  • the patient is also treated with an anticonvulsant mood stabilizer.
  • Anticonvulsant medications, particularly valproate and carbamazepine have been used as alternatives or adjuncts to lithium in many cases.
  • Valproate (Depakote, Epival) was FDA approved for the treatment of acute mania in 1995, and is now considered by some doctors to be the first line of therapy for bipolar disorder.
  • valproic acid (Depakene) is also used.
  • Anticonvulsants are also used in combination with antipsychotics. Newer anticonvulsant medications, including lamotrigine and oxcarbazepine, are also effective as mood stabilizers in bipolar disorder. Lamotrigine is particularly promising, as it alleviates bipolar depression and prevents recurrence at higher rates.
  • Zonisamide (trade name Zonegran), another anticonvulsant, also may show promise in treating bipolar depression. Topiramate maybe useful for some patients.
  • olanzapine Zyprexa
  • Eli Lilly and Company also offers Symbyax, a combination of olanzapine and fluoxetine.
  • Ziprasidone and aripriprazole (Abilify) also show promise.
  • Other newer treatments include Modafinil (Provigil) and Pramipexole (Mirapex), which show promise in treating the cognitive deterioration related to bipolar depression.
  • Riluzole an ALS treatment
  • the breast cancer medicine tamoxifen has shown quick response to manic phases.
  • the patient is also treated with electroconvulsive therapy.
  • Electroconvulsive therapy ECT is sometimes used to treat severe bipolar depression in cases where other treatments have failed and is 60 to 70 percent effective.
  • the patient is also treated with psychotherapy.
  • Other treatments include omega-3 fatty acids, particularly as a supplement to other medication. There are also reports that medical marijuana can help control the mood swings in some forms of bipolar disorder.
  • a dsRNA described herein is administered to a patient who has previously been treated with another therapeutic or counseling modality but which has provided less than optimal results.
  • a dsRNA targeting GSK-3 can be accompanied by a exercise regimen or by dietary restrictions.
  • a dsRNA featured in the invention can also be administered with a drug or combination of drugs for managing Type II diabetes, e.g., a sulfonylurea, a biguanide, an alpha-glucosidase inhibitor, a thiazolidinedione, a meglitinide, a D-phenylalanine derivative, an amylin synthetic derivatives, an incretin mimetic, or an insulin.
  • a drug or combination of drugs for managing Type II diabetes e.g., a sulfonylurea, a biguanide, an alpha-glucosidase inhibitor, a thiazolidinedione, a meglitinide, a D-phenylalanine derivative, an amylin synthetic derivatives, an incretin mimetic, or an insulin.
  • Exemplary insulins include regular insulins (Humulin®, Novolin®), insulin lispro (Humalog®), insulin aspart (Novolog®), insulin glulisine (Apidra®), prompt insulin zinc (Semilente®, slightly slower acting), inhaled insulin (Exubera®), intermediate-acting insulins, isophane insulin, neutral protamine Hagedorn (NPH), insulin zinc (Lente®), extended insulin zinc insulin (Ultralente®), insulin glargine (Lantus®), and insulin detemir (Levemir®).
  • the patient can also be provided with a chemotherapy agent, such as deoxycoformycin, cisplatin, cyclophosphamide, 5-fluorouracil, adriamycin, daunorubicin, tamoxifen aunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosure
  • chemotherapeutic agents may be used individually (e.g., deoxycoformycin and dsRNA), sequentially (e.g., antiviral and dsRNA for a period of time, followed by deoxycoformycin and dsRNA), or in combination with one or more other such agents (e.g., deoxycoformycin, antiviral and dsRNA, or deoxycoformycin, radiotherapy and dsRNA). Two or more combined compounds may be used together or sequentially.
  • dsRNAs described here can be used in combination with other GSK-3 inhibitors.
  • examples of such inhibitors described in Meijer et al., Trends in Pharmacological Sciences, 25: 471 (September 2004), incorporated herein by reference include pyrroloazepines, (e.g., hymenialdisine), flavones (e.g., flavopiridol), benzazepinones (e.g., kenpaullone, alsterpaulione, and azakenpaullone), bis-indole indirubin-3′-oximes (e.g., indirubin-3′-oxime, 6-bromoindirubin-3′-oxime (BIO), and 6-bromoindirubin-3′-acetoxime), pyrrolopyrazines (e.g., aloisine A and aloisine B), thiadiazolidinones (e.g., TDZD8), pyridylox
  • the invention provides a method for inhibiting the expression of an GSK-3 gene in a mammal.
  • the method includes administering a composition featured in the invention to the mammal such that expression of the target GSK-3 gene is silenced.
  • the composition may be administered by any means known in the art including, but not limited to oral or parenteral routes, including intravenous, intramuscular, subcutaneous, transdermal, airway (aerosol), nasal, rectal, and topical (including buccal and sublingual) administration.
  • oral or parenteral routes including intravenous, intramuscular, subcutaneous, transdermal, airway (aerosol), nasal, rectal, and topical (including buccal and sublingual) administration.
  • the compositions are administered by intravenous infusion or injection.
  • siRNAs with low off-target potential were defined as preferable and assumed to be more specific in vivo.
  • Off-target score (number of seed mismatches*2.8)+(number of cleavage site mismatches*1.2)+(number of non-seed mismatches*1)
  • the most relevant off-target gene for each siRNA corresponding to the input 19 mer sequence was defined as the gene with the lowest off-target score.
  • the candidate oligomers were ranked first by the lowest off-target score for the antisense sequence, and secondarily by the lowest off-target score by its sense counterpart.
  • the top 11 oligo sense and antisense pairs from the list were synthesized and their capacity for knockdown of the mouse GSK3 ⁇ transcript measured. The sequences are shown in Table 4.
  • Sense and antisense oligomers complementary to the human GSK3 ⁇ gene were designed by first aligning the orthologous transcripts, and then identifying the human counterpart region of the mouse candidate target regions. The sequences are shown in Table 6.
  • siRNAs with low off-target potential were defined as preferable and assumed to be more specific in vivo.
  • Off-target score (number of seed mismatches*2.8)+(number of cleavage site mismatches*1.2)+(number of non-seed mismatches*1)
  • the most relevant off-target gene for each siRNA corresponding to the input 19 mer sequence was defined as the gene with the lowest off-target score.
  • the candidate oligomers were ranked first by the lowest off-target score for the antisense sequence, and secondarily by the lowest off-target score by its sense counterpart.
  • the top 11 oligo sense and antisense pairs from the list were synthesized and their capacity for knockdown of the mouse Gsk3 ⁇ transcript measured. The sequences are shown in Table 5.
  • Sense and antisense oligomers complementary to the human GSK3 ⁇ gene were designed by first aligning the orthologous transcripts, and then identifying the human counterpart region of the mouse candidate target regions. The sequences are shown in Table 7.
  • nucleotide monomers used in nucleic acid sequence representation.
  • such reagent may be obtained from any supplier of reagents for molecular biology at a quality/purity standard for application in molecular biology.
  • RNAs Single-stranded RNAs can be produced by solid phase synthesis on a scale of 1 ⁇ mole using an Expedite 8909 synthesizer (Applied Biosystems, Applera Kunststoff GmbH, Darmstadt, Germany) and controlled pore glass (CPG, 500 ⁇ , Proligo Biochemie GmbH, Hamburg, Germany) as solid support.
  • RNA and RNA containing 2′-O-methyl nucleotides can be generated by solid phase synthesis employing the corresponding phosphoramidites and 2′-O-methyl phosphoramidites, respectively (Proligo Biochemie GmbH, Hamburg, Germany).
  • These building blocks can be incorporated at selected sites within the sequence of the oligoribonucleotide chain using standard nucleoside phosphoramidite chemistry such as described in Current protocols in nucleic acid chemistry, Beaucage, S. L. et al. (Edrs.), John Wiley & Sons, Inc., New York, N.Y., USA.
  • Phosphorothioate linkages can be introduced by replacement of the iodine oxidizer solution with a solution of the Beaucage reagent (Chruachem Ltd, Glasgow, UK) in acetonitrile (1%).
  • Further ancillary reagents can be obtained from Mallinckrodt Baker (Griesheim, Germany).
  • RNA can be generated by mixing an equimolar solution of complementary strands in annealing buffer (20 mM sodium phosphate, pH 6.8; 100 mM sodium chloride), heated in a water bath at 85-90° C. for 3 minutes and cooled to room temperature over a period of 3-4 hours.
  • the annealed RNA solution can be stored at ⁇ 20° C. until use.
  • RNA synthesis For the synthesis of 3′-cholesterol-conjugated siRNAs (herein referred to as -Chol-3′), an appropriately modified solid support can be used for RNA synthesis.
  • the modified solid support was prepared as follows:
  • a 4.7 M aqueous solution of sodium hydroxide (50 mL) can be added into a stirred, ice-cooled solution of ethyl glycinate hydrochloride (32.19 g, 0.23 mole) in water (50 mL). Then, ethyl acrylate (23.1 g, 0.23 mole) can be added and the mixture can be stirred at room temperature until completion of the reaction can be ascertained by TLC. After 19 h the solution can be partitioned with dichloromethane (3 ⁇ 100 mL). The organic layer can be dried with anhydrous sodium sulfate, filtered and evaporated. The residue can be distilled to afford AA (28.8 g, 61%).
  • Fmoc-6-amino-hexanoic acid (9.12 g, 25.83 mmol) can be dissolved in dichloromethane (50 mL) and cooled with ice.
  • Diisopropylcarbodiimde (3.25 g, 3.99 mL, 25.83 mmol) can be added to the solution at 0° C. It can then be followed by the addition of Diethyl-azabutane-1,4-dicarboxylate (5 g, 24.6 mmol) and dimethylamino pyridine (0.305 g, 2.5 mmol). The solution can be brought to room temperature and stirred further for 6 h. Completion of the reaction was ascertained by TLC.
  • the reaction mixture can be concentrated under vacuum and ethyl acetate can be added to precipitate diisopropyl urea.
  • the suspension can be filtered.
  • the filtrate can be washed with 5% aqueous hydrochloric acid, 5% sodium bicarbonate and water.
  • the combined organic layer can be dried over sodium sulfate and concentrated to give the crude product which can be purified by column chromatography (50% EtOAC/Hexanes) to yield 11.87 g (88%) of AB.
  • the hydrochloride salt of 3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethyl ester AC (4.7 g, 14.8 mmol) can be taken up in dichloromethane.
  • the suspension was cooled to 0° C. on ice.
  • diisopropylethylamine (3.87 g, 5.2 mL, 30 mmol) can be added.
  • cholesteryl chloroformate 6.675 g, 14.8 mmol
  • the reaction mixture can be stirred overnight.
  • the reaction mixture can be diluted with dichloromethane and washed with 10% hydrochloric acid.
  • the product can be purified by flash chromatography (10.3 g, 92%).
  • Potassium t-butoxide (1.1 g, 9.8 mmol) can be slurried in 30 mL of dry toluene. The mixture can be cooled to 0° C. on ice and 5 g (6.6 mmol) of diester AD can be added slowly with stirring within 20 mins. The temperature can be kept below 5° C. during the addition. The stirring can be continued for 30 mins at 0° C. and 1 mL of glacial acetic acid can be added, immediately followed by 4 g of NaH 2 PO 4 .H 2 O in 40 mL of water.
  • the resultant mixture can be extracted twice with 100 mL of dichloromethane each and the combined organic extracts can be washed twice with 10 mL of phosphate buffer each, dried, and evaporated to dryness.
  • the residue can be dissolved in 60 mL of toluene, cooled to 0° C. and extracted with three 50 mL portions of cold pH 9.5 carbonate buffer.
  • the aqueous extracts can be adjusted to pH 3 with phosphoric acid, and extracted with five 40 mL portions of chloroform which can be combined, dried and evaporated to dryness.
  • the residue can be purified by column chromatography using 25% ethylacetate/hexane to afford 1.9 g of b-ketoester (39%).
  • Diol AF (1.25 gm 1.994 mmol) can be dried by evaporating with pyridine (2 ⁇ 5 mL) in vacuo.
  • Anhydrous pyridine (10 mL) and 4,4′-dimethoxytritylchloride (0.724 g, 2.13 mmol) can be added with stirring.
  • the reaction can be carried out at room temperature overnight.
  • the reaction can be quenched by the addition of methanol.
  • the reaction mixture can be concentrated under vacuum and to the residue dichloromethane (50 mL) was added.
  • the organic layer can be washed with 1M aqueous sodium bicarbonate.
  • the organic layer can be dried over anhydrous sodium sulfate, filtered and concentrated.
  • the residual pyridine can be removed by evaporating with toluene.
  • Compound AG (1.0 g, 1.05 mmol) can be mixed with succinic anhydride (0.150 g, 1.5 mmol) and DMAP (0.073 g, 0.6 mmol) and dried in a vacuum at 40° C. overnight.
  • the mixture can be dissolved in anhydrous dichloroethane (3 mL), triethylamine (0.318 g, 0.440 mL, 3.15 mmol) can be added and the solution can be stirred at room temperature under argon atmosphere for 16 h. It can then be diluted with dichloromethane (40 mL) and washed with ice cold aqueous citric acid (5 wt %, 30 mL) and water (2 ⁇ 20 mL). The organic phase can be dried over anhydrous sodium sulfate and concentrated to dryness. The residue can be used as such for the next step.
  • Succinate AH (0.254 g, 0.242 mmol) can be dissolved in a mixture of dichloromethane/acetonitrile (3:2, 3 mL).
  • DMAP (0.0296 g, 0.242 mmol) in acetonitrile (1.25 mL)
  • 2,2′-Dithio-bis(5-nitropyridine) (0.075 g, 0.242 mmol) in acetonitrile/dichloroethane (3:1, 1.25 mL) can be added successively.
  • triphenylphosphine (0.064 g, 0.242 mmol) in acetonitrile (0.6 ml) was added.
  • the reaction mixture can turn bright orange in color.
  • the solution can be agitated briefly using a wrist-action shaker (5 mins).
  • Long chain alkyl amine-CPG (LCAA-CPG) (1.5 g, 61 mM) can be added.
  • the suspension can be agitated for 2 h.
  • the CPG was filtered through a sintered funnel and washed with acetonitrile, dichloromethane and ether successively. Unreacted amino groups can be masked using acetic anhydride/pyridine.
  • the achieved loading of the CPG can be measured by taking UV measurement (37 mM/g).
  • siRNAs bearing a 5′-12-dodecanoic acid bisdecylamide group (herein referred to as “5′-C32-”) or a 5′-cholesteryl derivative group (herein referred to as “5′-Chol-”) can be performed as described in WO 2004/065601, except that, for the cholesteryl derivative, the oxidation step can be performed using the Beaucage reagent in order to introduce a phosphorothioate linkage at the 5′-end of the nucleic acid oligomer.
  • Mouse HT22 cells were a gift from Dr. Marcy MacDonald and cultured in Dulbecco's modified Eagle's medium supplied with 10% fetal bovine serum and differentiated in modified serum-free medium (Dulbecco's modified Eagle's medium, N2 supplement, 50 ng/ml nerve growth factor- ⁇ , 100 ⁇ M phorbol 12,13-dibutyrate, 100 ⁇ M dibutyryl cAMP) for 24-48 h before treatment. All treatments were performed in differentiation medium with reduced nerve growth factor- ⁇ content (5 ng/ml) at 37° C. in a humidified incubator with 5% CO 2 .
  • Dulbecco's modified Eagle's medium supplied with 10% fetal bovine serum and differentiated in modified serum-free medium (Dulbecco's modified Eagle's medium, N2 supplement, 50 ng/ml nerve growth factor- ⁇ , 100 ⁇ M phorbol 12,13-dibutyrate, 100 ⁇ M dibutyryl cAMP) for 24-48 h before
  • siRNA HT22 cells were seeded at a density of 1.0 ⁇ 10 5 cells/well in 6-well tissue culture plates and transfected directly.
  • Transfection of siRNA (37.5 nM for single dose screen) was carried out with Lipofectamine-2000 (Invitrogen, Carlsbad, Calif.) as described by the manufacturer.
  • siRNA concentrations ranged from 10 nM to 0.1 nM in 10-fold dilutions.
  • HT22 cells were lysed and cDNA was generated for GSK3 ⁇ or GSK3 ⁇ and GAPDH mRNA quantitation.
  • GSK3 ⁇ or GSK3 ⁇ mRNA levels were normalized to GAPDH mRNA levels.
  • 2 individual data points were collected.
  • An siRNA duplex unrelated to the GSK3 ⁇ or GSK3 ⁇ gene was used as a control.
  • the activity of a given GSK3 ⁇ - or GSK313-specific siRNA duplex was expressed as the fraction of the GSK3 ⁇ or GSK3 ⁇ mRNA level in treated cells relative to the GSK3 ⁇ or GSK3 ⁇ mRNA level in cells treated with the control siRNA duplex.
  • Duplex identifier used in the Figures and in Examples 2-5 refer to the modified version of the duplex, e.g., AD-18821 as used in the Figures and Examples 2-5 refers to the modified version of AD-18821, e.g., AD-18821-b1.
  • FIG. 1 and FIG. 2 provide the results from the in vitro HT22 screen where the siRNAs were tested at a single dose of 37.5 nM.
  • a number of GSK3 ⁇ siRNAs (AD-18821, AD-18825 or AD-18832) at 37.5 nM were effective at reducing GSK3 ⁇ mRNA levels by more than 40%, without affecting GSK3 ⁇ mRNA levels, in HT22 cells.
  • GSK3 ⁇ siRNAs (AD-18833, AD-18834, AD-18836, AD-18837, AD-18838, AD-18841, AD-18842, AD-18843 or AD-18844) at 37.5 nM were effective at reducing GSK3 ⁇ mRNA levels by more than 40%, without affecting GSK3 ⁇ mRNA levels, in HT22 cells.
  • FIG. 3 and FIG. 4 show the dose-dependence of selected siRNAs on mRNA reduction in HT22 cells.
  • siRNAs targeting GSK3 ⁇ AD-18821, AD-18825 or AD-18826
  • IC50 values of less than or equal to 1-10 nM in suppressing GSK3 ⁇ mRNA after transfection into HT22 cells FIG. 3
  • siRNAs targeting GSK3 ⁇ AD-18838 or AD-18843
  • GSK3 ⁇ dsRNAs reduce endogenous GSK3 ⁇ protein in HT22 cells
  • HT22 cells were cultured and transfected as previously described with 75 nM of 11 siRNAs against GSK3 ⁇ (AD-18833, AD-18834, AD-18835, AD-18836, AD-18837, AD-18838, AD-18839, AD-18841, AD-18842, AD-18843 or AD-18844); one control unrelated siRNA (AD-1955) or Lipofectamine-2000 alone (Control). 48 hours post-transfection, the cells were harvested and lysed. Proteins in the lysates were separated on a denaturing polyacrylamide gel. GSK3 ⁇ and ⁇ -actin were detected by standard western blot protocols using antibodies that bind to the proteins.
  • the membrane was probed with a monoclonal GSK3 ⁇ antibody produced in rabbit (Cell Signaling, Danvers, Mass.) followed by a secondary antibody donkey anti-rabbit IgG horseradish peroxidase (GE Healthcare, Piscataway, N.J.).
  • ⁇ -actin was detected by mouse anti-actin antibody (Sigma, St. Louis, Mo.) followed by a Sheep anti-mouse IgG horseradish peroxidase secondary antibody (GE Healthcare, Piscataway, N.J.).
  • FIG. 5 provides the results.
  • These results demonstrate that dsRNAs targeting GSK3 ⁇ effectively reduce not only GSK3 ⁇ mRNA levels, but also GSK3 ⁇ protein levels.
  • dsRNAs targeting GSK3 ⁇ (AD-18821, AD-18825, and AD-18826) or GSK3 ⁇ (AD-18838, AD-18843, and AD-18844) were evaluated.
  • mice 1.26 mg AD-18821, AD-18825, AD-18826, AD-18838, AD-18843, AD-18844, or phosphate-buffered saline (PBS, vehicle control) was administered by continuous infusion into the nucleus accumbens over 14 days.
  • PBS phosphate-buffered saline
  • Ten week old male C57BL6 mice (Charles River Laboratory) received stereotaxic implantations of 30-gauge infusion cannulae (Plastics One, Roanok, Va.) such that unilateral infusions were targeted to the nucleus accumbens (anteroposterior +1.1 mm, mediolateral +1.3 mm, relative to bregma; dorsoventral 4.5 mm, relative to skull surface).
  • Mini-osmotic pumps (model 1002) were primed overnight according to the manufacturer's specifications, implanted subcutaneously, and connected via catheters, to deliver (6 mice per treatment group) PBS, 1.1 mM (15 mg/mL) of GSK3 ⁇ siRNAs (AD-18821, AD-18825, or AD-18826) or 1.1 mM (15 mg/mL) of GSK3 ⁇ siRNAs (AD-18838, AD-18843, or AD-18844) at 0.25 ⁇ L/hr over 14 days.
  • GSK3 ⁇ and GSK3 ⁇ mRNA were quantified for GSK3 ⁇ and GSK3 ⁇ mRNA.
  • Each brain punch was run in triplicate for RT-qPCR. Approximately 60 ng of total RNA in a 20 ⁇ l total reaction volume was used for RT-qPCR.
  • GSK3 ⁇ and GSK3 ⁇ primers were custom designed and obtained from IDT (Integrated DNA Technologies, Inc., Coralville, Iowa).
  • RT-qPCR was run with SBYR.
  • the human duplexes can be modified in a similar manner to the mouse duplexes.
  • the transfected cells are assayed for effects on mRNA and protein levels using techniques described herein and known to one of skill in the art.
  • the subject's condition is compared to the condition existing prior to the treatment, or relative to the condition of a similarly afflicted but untreated subject.
  • Target sequence location identifies target sequence in mouse GSK3-alpha mRNA NM_001031667.1. Unmodified sense strand is identical to target sequence. Unmodified a antisense strand is complementary to target sequence.
  • Target sequence location identifies target sequence in mouse GSK3-beta mRNA NM_019827.6.
  • Sense strand is identical to target sequence.
  • Antisense strand is complementary to target sequence.
  • Target SEQ SEQ sequence ID Unmodified sequence ID Modified sequence location NO: 5′ to 3′ NO: 5′ to 3′ Strand 1842-1861 8985 ACUGUAACAUAGUCCGACU 10985 AcuGuAAcAuAGuccGAcudTsdT sense 1842-1861 8986 AGUCGGACUAUGUUACAGU 10986 AGUCGGACuAUGUuAcAGUdTsdT antis 1843-1862 8987 CUGUAACAUAGUCCGACUG 10987 cuGuAAcAuAGuccGAcuGdTsdT sense 1843-1862 8988 CAGUCGGACUAUGUUACAG 10988 cAGUCGGACuAUGUuAcAGdTsdT antis 1952-1971 8989 GCCAGACACUAUAGUCGAG 10989 GccAGAcAcuAuAGucGAGdTsdT sense 1952-1971 8990 CUCGACUAUAGUGUCUGGC 10990 CUCGACuAuAGUGUCUGGCdTs
  • Target sequence start identifies first nucleotide in target sequence in mouse GSK3-alpha mRNA NM_001031667.1. Unmodified sense strand is identical to target sequence. Unmodified antisense strand is complementary to target sequence.
  • Target sequence SEQ ID unmodified sense strand SEQ unmodified antisense strand Duplex start NO: 5′ to 3′ ID NO: 5′ to 3′
  • AD-18821 670 12985 AACUGCAGAUUAUGCGUAA 12996 UUACGCAUAAUCUGCAGUU AD-18823 330 12986 GGCGGCGGGAAAGCGUCAG 12997 CUGACGCUUUCCCGCCGCC AD-18824 239 12987 GGCGCGGACCAGCUCGUUC 12998 GAACGAGCUGGUCCGCGCC AD-18825 1340 12988 CCUACUGGAGUACACGCCA 12999 UGGCGUGUACUCCAGUAGG AD-18826 1342 12989 UACUGGAGUACACGCCAUC 13000 GAUGGCGUGUACUCCAGUA AD-18827 1073 12990 CACAGAUUACACCUCGUCC 13001 GGACGAGGUGUAAUCUGUG AD-18828 1236 12991 CCUAACUAUACGGAGUUCA 13002
  • Target SEQ sequence ID unmodified sense strand SEQ ID unmodified antisense strand Duplex start NO: 5′ to 3′ NO: 5′ to 3′
  • AD-18833 1842 13029 ACUGUAACAUAGUCCGACU 13040
  • AGUCGGACUAUGUUACAGU AD-18834 1843 13030 CUGUAACAUAGUCCGACUG 13041
  • CAGUCGGACUAUGUUACAG AD-18835 1952 13031
  • GCCAGACACUAUAGUCGAG 13042 CUCGACUAUAGUGUCUGGC AD-18836 1847 13032
  • AACAUAGUCCGACUGCGGU 13043 ACCGCAGUCGGACUAUGUU AD-18837 1838 13033
  • GACCACUGUAACAUAGUCC 13044 GGACUAUGUUACAGUGGUC AD-18838 1846 13034 UAACAUAGUCCGACUGCGG 13045 CCGCAGUCGGACUAUGUUA AD-18839 1849 13035 CAUAGUCCGACUGCGGUAU 13046 AUACCGCAG
  • Target sequence start identifies first nucleotide in target sequence in human GSK3-alpha mRNA NM_002093. Unmodified sense strand is identical to target sequence. Unmodified antisense strand is complementary to target sequence.
  • Target sequence SEQ ID unmodified sense strand SEQ ID unmodified antisense strand Duplex start NO: 5′ to 3′ NO: 5′ to 3′ huGSKA-1 1273 13073 AGCUCCAGAUCAUGAGAAA 13081 UUUCUCAUGAUCUGGAGCU huGSKA-2 1979 13074 UCUGCUGGAGUAUACACCA 13082 UGGUGUAUACUCCAGCAGA huGSKA-3 1981 13075 UGCUGGAGUAUACACCAAC 13083 GUUGGUGUAUACUCCAGCA huGSKA-4 1676 13076 CACUGAUUAUACCUCUAGU 13084 ACUAGAGGUAUAAUCAGUG huGSKA-5 1839 13077 CCAAACUACACAGAAUUUA 13085 UAAAUUCUGUGUAGUUUGG huGSKA-6 1834 13078 UGAACCCAAACUACACAGA 13086 UCUGUGUAGUUUGGGUUCA huGSKA-7 1837 13079 ACCCAAACUACACAGAAUU
  • Target sequence SEQ unmodified sense strand SEQ unmodified antisense strand Duplex start ID NO: 5′ to 3′ ID NO: 5′ to 3′ huGSKB-1 625 13088 ACUGCAAUAUUGUGAGGCU 13099 AGCCUCACAAUAUUGCAGU huGSKB-2 626 13089 CUGCAAUAUUGUGAGGCUG 13100 CAGCCUCACAAUAUUGCAG huGSKB-3 735 13090 GCCCGCCACUUCACCAAGG 13101 CCUUGGUGAAGUGGCGGGC huGSKB-4 630 13091 AAUAUUGUGAGGCUGAGAU 13102 AUCUCAGCCUCACAAUAUU huGSKB-5 621 13092 GACCACUGCAAUAUUGUGA 13103 UCACAAUAUUGCAGUGGUC huGSKB-6 629 13093 CAAUAUUGUGAGGCUGAGA 13104 UCUCAGCCUCACAAUAUUG huGSKB-7 632 13094 UAUUGUGAGGCUGAGAUAC 13105 GUA

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Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting Glycogen Synthase Kinase-3 (GSK-3), and methods of using the dsRNA to inhibit expression of GSK-3.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application claims the benefit of U.S. Provisional Application No. 61/080,153, filed Jul. 11, 2008, which is hereby incorporated in its entirety by reference.
  • STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
  • None.
  • FIELD OF THE INVENTION
  • The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting Glycogen Synthase Kinase-3 alpha and/or beta (GSK-3 alpha and/or beta), and methods of using the dsRNA to inhibit expression of GSK-3. alpha and/or beta.
  • BACKGROUND OF THE INVENTION
  • Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine kinase. It functions as a key regulator of numerous signaling pathways. It phosphorylates and inactivates glycogen synthase, a key enzyme in glycogen metabolism. It has also been shown to be involved in the regulation of a diverse array of cellular functions, including protein synthesis, cell proliferation, cell differentiation, microtubule assembly/disassembly, and apoptosis. Two isoforms of GSK-3 have been reported in mammals: an approximately 51 kDa GSK-3 alpha form and an approximately 47 kDa GSK-3 beta form. These two isoforms exhibit about 98% homology in their kinase domains. Other regions share less homology: they share only about 36% identity in the last 76 C-terminal amino acid residues.
  • Double-stranded RNA molecules (dsRNA) have been shown to block gene expression in a highly conserved regulatory mechanism known as RNA interference (RNAi). WO 99/32619 (Fire et al.) disclosed the use of a dsRNA of at least 25 nucleotides in length to inhibit the expression of genes in C. elegans. dsRNA has also been shown to degrade target RNA in other organisms, including plants (see, e.g., WO 99/53050, Waterhouse et al.; and WO 99/61631, Heifetz et al.), Drosophila (see, e.g., Yang, D., et al., Curr. Biol. (2000) 10:1191-1200), and mammals (see WO 00/44895, Limmer; and DE 101 00 586.5, Kreutzer et al.).
  • SUMMARY OF THE INVENTION
  • The invention provides compositions containing double-stranded ribonucleic acid (dsRNA) targeted to a GSK-3 gene and methods for inhibiting the expression of a GSK-3 gene in a cell or mammal. The composition can inhibit GSK-3 alpha and/or GSK-3 beta. A composition that inhibits both can do so, e.g., by including a dsRNA that targets both GSK-3 alpha and GSK-3 beta, or by including a first dsRNA that inhibits GSK-3 alpha and a second dsRNA that inhibits GSK-3 beta. The composition can also include a dsRNA which inhibits both and a second which inhibits only one of the isoforms.
  • The invention also provides compositions and methods for treating manic depression (bipolar disorder).
  • Other disorders, e.g., pathological conditions and diseases caused by the expression of a GSK-3 gene, such as metabolic disorders (e.g., Type I or Type II diabetes or metabolic syndrome) and nervous system disorders, (e.g., CNS and nuerogenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, Huntington's Disease, bipolar disorder, prion diseases (e.g., transmissible spongiform encephalopathies), stroke and schizophrenia). Compositions and methods for treating pathological conditions and diseases such as protozoan diseases (e.g., Plasmodium falciparum), cancer (e.g., colorectal cancer), and circadian rhythm diseases (e.g., sleep disorders, jet lag, and shift work), are also provided. The dsRNAs described herein can also be used to regulate skeletal muscle growth, inflammatory responses, platelet function, apoptosis, and cellular responses to DNA damage.
  • In one embodiment the invention provides a double-stranded ribonucleic acid (dsRNA), having a sense strand and an antisense strand, the sense strand comprising a first sequence and the antisense strand comprising a second sequence, the second sequence comprising a region complementary to an mRNA encoding a GSK-3 gene, and wherein said region of complementarity is less than 30 nucleotides in length. In some embodiments, the second sequence includes a region complementary to the GSK-3 gene sequences NM019884, NM00103166, :NM002093, or NM019827. In other embodiments, the second sequence includes a region complementary to at least 15 nucleotides of a target sequence described herein, e.g., in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7. The second sequence can include a region complementary to a target sequence described in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • The antisense strand of the dsRNA of the invention can include at least 15 nucleotides of one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7. In one embodiment, the antisense strand includes one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7. In another embodiment, the antisense strand consists of one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • The sense strand can include at least 15 nucleotides of one of the sense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7. For example, the sense strand can include or can consist of one of the sense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • In some embodiments, the dsRNA of the invention consists of one of the sense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 and the antisense strand consists of one of the antisense strand sequences in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7. Further embodiments include the duplexes disclosed herein, e.g., huGSKA-3, huGSKB-11, AD-18821, AD-18825, AD-18826, AD-18838, AD-18843, or AD-18844.
  • The dsRNA of the invention can include at least one modified nucleotide. Disclosed herein are exemplary modified sequences, but one of skill can readily design duplexes with different set of modifications using the sequences and teachings herein. The modified nucleotides can be, e.g., a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, or a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group. The modified nucleotide(s) can be a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide. In one embodiment the dsRNA of the invention includes at least one 2′-O-methyl modified nucleotide and at least one nucleotide comprising a 5′-phosphorothioate group.
  • The region of complementarity of the dsRNA of the invention is less than 30 nucleotides, e.g., at least 15 nucleotides in length, or, e.g., between 19 and 21 nucleotides in length, or, e.g., 19 nucleotides in length.
  • Disclosed and claimed herein are methods for inhibiting expression of a GSK-3 gene. In one embodiment, administration of the dsRNA inhibits expression of GSK3 by more than 40%. In another embodiment the dsRNA exhibits an IC50 of less than or equal to 10 nM in suppressing GSK3. Alternatively, the dsRNA exhibits an IC50 of less than or equal to 1.0 nM in suppressing GSK3.
  • Also included in the invention are cells and vectors comprising the dsRNA of the invention.
  • Further contemplated is a pharmaceutical composition for inhibiting expression of an GSK-3 gene comprising a dsRNA of the invention.
  • Methods of inhibiting GSK-3 expression in a cell are included in the invention. The methods include (a) introducing into the cell the dsRNA of the invention; and (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a GSK-3 gene, thereby inhibiting expression of a GSK-3 gene in the cell.
  • Also included is a method of treating a disorder mediated by GSK-3 expression comprising administering to a human in need of such treatment a therapeutically effective amount of a dsRNA of the invention, including treatment of manic depression.
  • BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
  • These and other features, aspects, and advantages of the present invention will become better understood with regard to the following description, and accompanying drawings, where:
  • FIG. 1 is a graph illustrating the results of GSK3α mRNA suppression in HT22 cells 24 hours after 37.5 nM siRNA transfection.
  • FIG. 2 is a graph illustrating the results of GSK3β mRNA suppression in HT22 cells 24 hours after 37.5 nM siRNA transfection.
  • FIG. 3 is a graph illustrating the dose dependence of GSK3α mRNA suppression after siRNA transfection of HT22 cells.
  • FIG. 4 is a graph illustrating the dose dependence of GSK3 β mRNA suppression after siRNA transfection of HT22 cells.
  • FIG. 5 is a western blot illustrating protein levels after siRNA transfection in HT22 cells.
  • FIG. 6 is a graph illustrating GSK3β mRNA suppression in mouse nucleus accumbens after 14 day infusion of AD-18844 into the nucleus accumbens.
  • FIG. 7 is a graph illustrating GSK3α mRNA suppression in mouse nucleus accumbens after 14 day infusion of AD-18826 into the nucleus accumbens.
  • DETAILED DESCRIPTION OF THE INVENTION
  • The invention provides dsRNAs and methods of using the dsRNAs for inhibiting the expression of a GSK-3 gene in a cell or a mammal where the dsRNA targets a GSK-3 gene. The invention also provides compositions and methods for treating pathological conditions and diseases, such as a metabolic disease or a cardiovascular disease, in a mammal caused by the expression of a GSK-3 gene. dsRNA directs the sequence-specific degradation of mRNA through a process known as RNA interference (RNAi).
  • The dsRNAs of the compositions featured herein include an RNA strand (the antisense strand) having a region which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an mRNA transcript of a GSK-3 gene. The use of these dsRNAs enables the targeted degradation of mRNAs of genes that are implicated in replication and or maintenance of cancer cells in mammals. Very low dosages of GSK-3 dsRNAs in particular can specifically and efficiently mediate RNAi, resulting in significant inhibition of expression of the GSK-3 gene. The methods and compositions of the invention containing the GSK-3 dsRNA are useful for treating pathological processes mediated by GSK-3 expression, e.g., manic depression, or other disorders described herein.
  • The following detailed description discloses how to make and use the compositions containing dsRNAs to inhibit the expression of a GSK-3 gene, as well as compositions and methods for treating diseases and disorders caused by the expression of these genes, such as manic depression. The pharmaceutical compositions featured in the invention include a dsRNA having an antisense strand comprising a region of complementarity which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an RNA transcript of a GSK-3 gene, together with a pharmaceutically acceptable carrier. The compositions featured in the invention also include a dsRNA having an antisense strand having a region of complementarity which is less than 30 nucleotides in length, generally 19-24 nucleotides in length, and is substantially complementary to at least part of an RNA transcript of a GSK-3 gene.
  • Accordingly, certain aspects of the invention provide pharmaceutical compositions containing the GSK-3 dsRNA and a pharmaceutically acceptable carrier, methods of using the compositions to inhibit expression of a GSK-3 gene, and methods of using the pharmaceutical compositions to treat diseases caused by expression of the GSK-3 gene.
  • I. DEFINITIONS
  • For convenience, the meaning of certain terms and phrases used in the specification, examples, and appended claims, are provided below. If there is an apparent discrepancy between the usage of a term in other parts of this specification and its definition provided in this section, the definition in this section shall prevail.
  • “G,” “C,” “A” and “U” each generally stand for a nucleotide that contains guanine, cytosine, adenine, and uracil as a base, respectively. “T” and “dT” are used interchangeably herein and refer to a deoxyribonucleotide wherein the nucleobase is thymine, e.g., deoxyribothymine. However, it will be understood that the term “ribonucleotide” or “nucleotide” or “deoxyribonucleotide” can also refer to a modified nucleotide, as further detailed below, or a surrogate replacement moiety. The skilled person is well aware that guanine, cytosine, adenine, and uracil may be replaced by other moieties without substantially altering the base pairing properties of an oligonucleotide comprising a nucleotide bearing such replacement moiety. For example, without limitation, a nucleotide comprising inosine as its base may base pair with nucleotides containing adenine, cytosine, or uracil. Hence, nucleotides containing uracil, guanine, or adenine may be replaced in the nucleotide sequences of the invention by a nucleotide containing, for example, inosine. Sequences comprising such replacement moieties are embodiments of the invention.
  • As used herein, “GSK-3” refers to Glycogen Synthase Kinase-3, which is also known as DKFZp686D0638, GSK3, C86142, GSK-3beta, 7330414F15Rik, and 8430431H08Rik. GSK-3 alpha sequence can be found as NCBI GeneID:2931 (human) and 606496 (mouse) and RefSeq ID number:NM019884 (human) and NM001031667 (mouse). GSK-3 beta sequence can be found as NCBI GeneID:2932 (human) and 56637 (mouse) and RefSeq ID number:NM002093 (human) and NM019827 (mouse). A dsRNA featured in the invention can target a specific GSK-3 isoform, e.g. GSK-3 alpha or GSK-3 beta, or a dsRNA of the invention can target both isoforms by binding to a common region of the mRNA transcript. A dsRNA featured in the invention can target a specific GSK-3 beta isoform, e.g. GSK-3 beta 1 or GSK-3 beta 2, or a dsRNA of the invention can target both isoforms by binding to a common region of the mRNA transcript.
  • As used herein, “target sequence” refers to a contiguous portion of the nucleotide sequence of an mRNA molecule formed during the transcription of a GSK-3 gene, including mRNA that is a product of RNA processing of a primary transcription product.
  • As used herein, the term “strand comprising a sequence” refers to an oligonucleotide comprising a chain of nucleotides that is described by the sequence referred to using the standard nucleotide nomenclature.
  • As used herein, and unless otherwise indicated, the term “complementary,” when used to describe a first nucleotide sequence in relation to a second nucleotide sequence, refers to the ability of an oligonucleotide or polynucleotide comprising the first nucleotide sequence to hybridize and form a duplex structure under certain conditions with an oligonucleotide or polynucleotide comprising the second nucleotide sequence, as will be understood by the skilled person. Such conditions can, for example, be stringent conditions, where stringent conditions may include: 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50° C. or 70° C. for 12-16 hours followed by washing. Other conditions, such as physiologically relevant conditions as may be encountered inside an organism, can apply. The skilled person will be able to determine the set of conditions most appropriate for a test of complementarity of two sequences in accordance with the ultimate application of the hybridized nucleotides.
  • This includes base-pairing of the oligonucleotide or polynucleotide comprising the first nucleotide sequence to the oligonucleotide or polynucleotide comprising the second nucleotide sequence over the entire length of the first and second nucleotide sequence. Such sequences can be referred to as “fully complementary” with respect to each other herein. However, where a first sequence is referred to as “substantially complementary” with respect to a second sequence herein, the two sequences can be fully complementary, or they may form one or more, but generally not more than 4, 3 or 2 mismatched base pairs upon hybridization, while retaining the ability to hybridize under the conditions most relevant to their ultimate application. However, where two oligonucleotides are designed to form, upon hybridization, one or more single stranded overhangs, such overhangs shall not be regarded as mismatches with regard to the determination of complementarity. For example, a dsRNA comprising one oligonucleotide 21 nucleotides in length and another oligonucleotide 23 nucleotides in length, wherein the longer oligonucleotide comprises a sequence of 21 nucleotides that is fully complementary to the shorter oligonucleotide, may yet be referred to as “fully complementary” for the purposes of the invention.
  • “Complementary” sequences, as used herein, may also include, or be formed entirely from, non-Watson-Crick base pairs and/or base pairs formed from non-natural and modified nucleotides, in as far as the above requirements with respect to their ability to hybridize are fulfilled. Such non-Watson-Crick base pairs includes, but not limited to, G:U Wobble or Hoogstein base pairing.
  • The terms “complementary”, “fully complementary” and “substantially complementary” herein may be used with respect to the base matching between the sense strand and the antisense strand of a dsRNA, or between the antisense strand of a dsRNA and a target sequence, as will be understood from the context of their use.
  • As used herein, a polynucleotide which is “substantially complementary to at least part of” a messenger RNA (mRNA) refers to a polynucleotide which is substantially complementary to a contiguous portion of the mRNA of interest (e.g., encoding a GSK-3) including a 5′ UTR, an open reading frame (ORF), or a 3′ UTR. For example, a polynucleotide is complementary to at least a part of a GSK-3 mRNA if the sequence is substantially complementary to a non-interrupted portion of an mRNA encoding a GSK-3.
  • The term “double-stranded RNA” or “dsRNA”, as used herein, refers to a complex of ribonucleic acid molecules, having a duplex structure comprising two anti-parallel and substantially complementary, as defined above, nucleic acid strands. In general, the majority of nucleotides of each strand are ribonucleotides, but as described in detail herein, each or both strands can also include at least one non-ribonucleotide, e.g., a deoxyribonucleotide and/or a modified nucleotide. In addition, as used in this specification, “dsRNA” may include chemical modifications to ribonucleotides, including substantial modifications at multiple nucleotides and including all types of modifications disclosed herein or known in the art. Any such modifications, as used in an siRNA type molecule, are encompassed by “dsRNA” for the purposes of this specification and claims. The two strands forming the duplex structure may be different portions of one larger RNA molecule, or they may be separate RNA molecules. Where the two strands are part of one larger molecule, and therefore are connected by an uninterrupted chain of nucleotides between the 3′-end of one strand and the 5′ end of the respective other strand forming the duplex structure, the connecting RNA chain is referred to as a “hairpin loop”. Where the two strands are connected covalently by means other than an uninterrupted chain of nucleotides between the 3′-end of one strand and the 5′ end of the respective other strand forming the duplex structure, the connecting structure is referred to as a “linker”. The RNA strands may have the same or a different number of nucleotides. The maximum number of base pairs is the number of nucleotides in the shortest strand of the dsRNA minus any overhangs that are present in the duplex. In addition to the duplex structure, a dsRNA may comprise one or more nucleotide overhangs.
  • As used herein, a “nucleotide overhang” refers to the unpaired nucleotide or nucleotides that protrude from the duplex structure of a dsRNA when a 3′-end of one strand of the dsRNA extends beyond the 5′-end of the other strand, or vice versa. “Blunt” or “blunt end” means that there are no unpaired nucleotides at that end of the dsRNA, i.e., no nucleotide overhang. A “blunt ended” dsRNA is a dsRNA that is double-stranded over its entire length, i.e., no nucleotide overhang at either end of the molecule.
  • The term “antisense strand” refers to the strand of a dsRNA which includes a region that is substantially complementary to a target sequence. As used herein, the term “region of complementarity” refers to the region on the antisense strand that is substantially complementary to a sequence, for example a target sequence, as defined herein. Where the region of complementarity is not fully complementary to the target sequence, the mismatches are most tolerated in the terminal regions and, if present, are generally in a terminal region or regions, e.g., within 6, 5, 4, 3, or 2 nucleotides of the 5′ and/or 3′ terminus.
  • The term “sense strand,” as used herein, refers to the strand of a dsRNA that includes a region that is substantially complementary to a region of the antisense strand.
  • “Introducing into a cell”, when referring to a dsRNA, means facilitating uptake or absorption into the cell, as is understood by those skilled in the art. Absorption or uptake of dsRNA can occur through unaided diffusive or active cellular processes, or by auxiliary agents or devices. The meaning of this term is not limited to cells in vitro; a dsRNA may also be “introduced into a cell”, wherein the cell is part of a living organism. In such instance, introduction into the cell will include the delivery to the organism. For example, for in vivo delivery, dsRNA can be injected into a tissue site or administered systemically. In vitro introduction into a cell includes methods known in the art such as electroporation and lipofection.
  • The terms “silence” and “inhibit the expression of” “down-regulate the expression of,” “suppress the expression of” and the like in as far as they refer to a GSK-3 gene, herein refer to the at least partial suppression of the expression of a GSK-3 gene, as manifested by a reduction of the amount of mRNA which may be isolated from a first cell or group of cells in which a GSK-3 gene is transcribed and which has or have been treated such that the expression of a GSK-3 gene is inhibited, as compared to a second cell or group of cells substantially identical to the first cell or group of cells but which has or have not been so treated (control cells). The degree of inhibition is usually expressed in terms of
  • ( mRNA in control cells ) - ( mRNA in treated cells ) ( mRNA in control cells ) · 100 %
  • Alternatively, the degree of inhibition may be given in terms of a reduction of a parameter that is functionally linked to GSK-3 gene transcription, e.g., the amount of protein encoded by a GSK-3 gene which is secreted by a cell, or the number of cells displaying a certain phenotype, e.g., apoptosis. In principle, GSK-3 gene silencing may be determined in any cell expressing the target, either constitutively or by genomic engineering, and by any appropriate assay. However, when a reference is needed in order to determine whether a given dsRNA inhibits the expression of the GSK-3 gene by a certain degree and therefore is encompassed by the instant invention, the assay provided in the Examples below shall serve as such reference.
  • For example, in certain instances, expression of a GSK-3 gene is suppressed by at least about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by administration of the double-stranded oligonucleotide of the invention. In some embodiments, a GSK-3 gene is suppressed by at least about 60%, 70%, or 80% by administration of the double-stranded oligonucleotide of the invention. In some embodiments, a GSK-3 gene is suppressed by at least about 85%, 90%, or 95% by administration of the double-stranded oligonucleotide of the invention.
  • As used herein in the context of GSK-3 expression, the terms “treat”, “treatment”, and the like, refer to relief from or alleviation of pathological processes mediated by GSK-3 expression. In the context of the present invention insofar as it relates to any of the other conditions recited herein below (other than pathological processes mediated by GSK-3 expression), the terms “treat”, “treatment”, and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression of such condition, such as the slowing and progression of manic depression.
  • As used herein, the phrases “therapeutically effective amount” and “prophylactically effective amount” refer to an amount that provides a therapeutic benefit in the treatment, prevention, or management of pathological processes mediated by GSK-3 expression or an overt symptom of pathological processes mediated by GSK-3 expression. The specific amount that is therapeutically effective can be readily determined by ordinary medical practitioner, and may vary depending on factors known in the art, such as, e.g. the type of pathological processes mediated by GSK-3 expression, the patient's history and age, the stage of pathological processes mediated by GSK-3 expression, and the administration of other anti-pathological processes mediated by GSK-3 expression agents.
  • As used herein, a “pharmaceutical composition” comprises a pharmacologically effective amount of a dsRNA and a pharmaceutically acceptable carrier. As used herein, “pharmacologically effective amount,” “therapeutically effective amount” or simply “effective amount” refers to that amount of an RNA effective to produce the intended pharmacological, therapeutic or preventive result. For example, if a given clinical treatment is considered effective when there is at least a 25% reduction in a measurable parameter associated with a disease or disorder, a therapeutically effective amount of a drug for the treatment of that disease or disorder is the amount necessary to effect at least a 25% reduction in that parameter.
  • The term “pharmaceutically acceptable carrier” refers to a carrier for administration of a therapeutic agent. Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. The term specifically excludes cell culture medium. For drugs administered orally, pharmaceutically acceptable carriers include, but are not limited to pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose, while corn starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatin, while the lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract.
  • As used herein, a “transformed cell” is a cell into which a vector has been introduced from which a dsRNA molecule may be expressed.
  • II. DOUBLE-STRANDED RIBONUCLEIC ACID (dsRNA)
  • As described in more detail herein, the invention provides double-stranded ribonucleic acid (dsRNA) molecules for inhibiting the expression of a GSK-3 gene in a cell or mammal, e.g., in a human having manic depression, or another disorder described herein, where the dsRNA includes an antisense strand having a region of complementarity which is complementary to at least a part of an mRNA formed in the expression of a GSK-3 gene, and where the region of complementarity is less than 30 nucleotides in length, and where said dsRNA, upon contact with a cell expressing a GSK-3 gene, inhibits the expression of a GSK-3 gene, e.g., by at least 30% as assayed by, for example, a PCR or branched DNA (bDNA) based method. The dsRNA of the invention may further include one or more single-stranded nucleotide overhangs.
  • The dsRNA can be synthesized by standard methods known in the art as further discussed below, e.g., by use of an automated DNA synthesizer, such as are commercially available from, for example, Biosearch, Applied Biosystems, Inc.
  • The dsRNA includes two RNA strands that are sufficiently complementary to hybridize to form a duplex structure. One strand of the dsRNA (the antisense strand) includes a region of complementarity that is substantially complementary, and generally fully complementary, to a target sequence, derived from the sequence of an mRNA formed during the expression of the GSK-3 gene, the other strand (the sense strand) includes a region that is complementary to the antisense strand, such that the two strands hybridize and form a duplex structure when combined under suitable conditions. Generally, the duplex structure is between 15 and 30, or between 25 and 30, or between 18 and 25, or between 19 and 24, or between 19 and 21, or 19, 20, or 21 base pairs in length. In one embodiment the duplex is 19 base pairs in length. In another embodiment the duplex is 21 base pairs in length. When two different siRNAs are used in combination, the duplex lengths can be identical or can differ.
  • Similarly, the region of complementarity to the target sequence can be between 15 and 30, or between 25 and 30, or between 18 and 25, or between 19 and 24, or between 19 and 21, or 19, 20, or 21 base pairs in length. In one embodiment the region of complementarity is 19 nucleotides in length. In another embodiment the region of complementarity is 21 nucleotides in length. When two different siRNAs are used in combination, the region of complementarity can be identical or can differ.
  • Each strand of the dsRNA of invention is generally between 15 and 30, or between 18 and 25, or 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length. In other embodiments, each is strand is 25-30 nucleotides in length. Each strand of the duplex can be the same length or of different lengths. When two different siRNAs are used in combination, the lengths of each strand of each siRNA can be identical or can differ.
  • The dsRNA of the invention can include one or more single-stranded overhang(s) of one or more nucleotides. In one embodiment, at least one end of the dsRNA has a single-stranded nucleotide overhang of 1 to 4, generally 1 or 2 nucleotides. In another embodiment, the antisense strand of the dsRNA has 1-10 nucleotides overhangs each at the 3′ end and the 5′ end over the sense strand. In further embodiments, the sense strand of the dsRNA has 1-10 nucleotides overhangs each at the 3′ end and the 5′ end over the antisense strand.
  • A dsRNAs having at least one nucleotide overhang can have unexpectedly superior inhibitory properties than the blunt-ended counterpart. In some embodiments the presence of only one nucleotide overhang strengthens the interference activity of the dsRNA, without affecting its overall stability. A dsRNA having only one overhang has proven particularly stable and effective in vivo, as well as in a variety of cells, cell culture mediums, blood, and serum. Generally, the single-stranded overhang is located at the 3′-terminal end of the antisense strand or, alternatively, at the 3′-terminal end of the sense strand. The dsRNA can also have a blunt end, generally located at the 5′-end of the antisense strand. Such dsRNAs can have improved stability and inhibitory activity, thus allowing administration at low dosages, i.e., less than 5 mg/kg body weight of the recipient per day. Generally, the antisense strand of the dsRNA has a nucleotide overhang at the 3′-end, and the 5′-end is blunt. In another embodiment, one or more of the nucleotides in the overhang is replaced with a nucleoside thiophosphate.
  • In one embodiment, the targeted GSK-3 gene is the human GSK-3 gene. In another embodiment, the targeted GSK-3 gene is a mouse gene. In some embodiments, the sense strand of the dsRNA includes a sense sequence from Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7, and the antisense sequence includes an antisense sequence of Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7. Alternative antisense agents that target elsewhere in the target sequence provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 can readily be determined using the target sequence and the flanking GSK-3 sequence.
  • The skilled person is well aware that dsRNAs comprising a duplex structure of between 20 and 23, but specifically 21, base pairs have been hailed as particularly effective in inducing RNA interference (Elbashir et al., EMBO 2001, 20:6877-6888). However, others have found that shorter or longer dsRNAs can be effective as well. In the embodiments described above, by virtue of the nature of the oligonucleotide sequences provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7, the dsRNAs of the invention can include at least one strand of a length of minimally 21 nt. It can be reasonably expected that shorter dsRNAs having one of the sequences of Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 minus only a few nucleotides on one or both ends may be similarly effective as compared to the dsRNAs described above. Hence, dsRNAs having a partial sequence of at least 15, 16, 17, 18, 19, 20, or more contiguous nucleotides from one of the sequences of Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7, and differing in their ability to inhibit the expression of a GSK-3 gene in an assay as described herein below by not more than 5, 10, 15, 20, 25, or 30% inhibition from a dsRNA comprising the full sequence, are contemplated by the invention. Further dsRNAs that cleave within the target sequence provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 can readily be made using the GSK-3 sequence and the target sequence provided.
  • In addition, the siRNA agents provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 identify a site in a GSK-3 mRNA that is susceptible to siRNA based cleavage. As such the present invention further features siRNA agents that target within the sequence targeted by one of the agents of the present invention. As used herein a second siRNA agent is said to target within the sequence of a first siRNA agent if the second siRNA agent cleaves the message anywhere within the mRNA that is complementary to the antisense strand of the first siRNA agent. Such a second agent will generally consist of at least 15 contiguous nucleotides from one of the sequences provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7 coupled to additional nucleotide sequences taken from the region contiguous to the selected sequence in the GSK-3 gene. For example, the last 15 nucleotides of SEQ ID NO:1 combined with the next 6 nucleotides from the target GSK-3 gene produces a single strand agent of 21 nucleotides that is based on one of the sequences provided in Table 1 or Table 2 or Table 4 or Table 5 or Table 6 or Table 7.
  • The dsRNA of the invention can contain one or more mismatches to the target sequence. In a preferred embodiment, the dsRNA of the invention contains no more than 3 mismatches. If the antisense strand of the dsRNA contains mismatches to a target sequence, it is preferable that the area of mismatch not be located in the center of the region of complementarity. If the antisense strand of the dsRNA contains mismatches to the target sequence, it is preferable that the mismatch be restricted to 5 nucleotides from either end, for example 5, 4, 3, 2, or 1 nucleotide from either the 5′ or 3′ end of the region of complementarity. For example, for a 23 nucleotide dsRNA strand which is complementary to a region of the GSK-3 gene, the dsRNA generally does not contain any mismatch within the central 13 nucleotides. The methods described within the invention can be used to determine whether a dsRNA containing a mismatch to a target sequence is effective in inhibiting the expression of a GSK-3 gene. Consideration of the efficacy of dsRNAs with mismatches in inhibiting expression of a GSK-3 gene is important, especially if the particular region of complementarity in a GSK-3 gene is known to have polymorphic sequence variation within the population.
  • In some embodiments the sense and/or antisense sequences of the dsRNA molecules featured herein can have the primary sequence shown in the tables with or without the modifications shown in the tables. In other embodiments the dsRNA molecule can differ by not more than 1, 2 or 3 bases from that provided in the tables.
  • In one embodiment, at least one end of the dsRNA has a single-stranded nucleotide overhang of 1 to 4, generally 1 or 2 nucleotides. dsRNAs having at least one nucleotide overhang have superior inhibitory properties than their blunt-ended counterparts. The presence of only one nucleotide overhang strengthens the interference activity of the dsRNA, without affecting its overall stability. dsRNA having only one overhang has proven particularly stable and effective in vivo, as well as in a variety of cells, cell culture mediums, blood, and serum. Generally, the single-stranded overhang is located at the 3′-terminal end of the antisense strand or, alternatively, at the 3′-terminal end of the sense strand. The dsRNA may also have a blunt end, generally located at the 5′-end of the antisense strand. Such dsRNAs have improved stability and inhibitory activity, thus allowing administration at low dosages, i.e., less than 5 mg/kg body weight of the recipient per day. Generally, the antisense strand of the dsRNA has a nucleotide overhang at the 3′-end, and the 5′-end is blunt. In another embodiment, one or more of the nucleotides in the overhang is replaced with a nucleoside thiophosphate.
  • Modifications
  • In yet another embodiment, the dsRNA is chemically modified to enhance stability. The nucleic acids of the invention may be synthesized and/or modified by methods well established in the art, such as those described in “Current protocols in nucleic acid chemistry”, Beaucage, S. L. et al. (Edrs.), John Wiley & Sons, Inc., New York, N.Y., USA, which is hereby incorporated herein by reference. Specific examples of preferred dsRNA compounds useful in this invention include dsRNAs containing modified backbones or no natural internucleoside linkages. As defined in this specification, dsRNAs having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified dsRNAs that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides.
  • Preferred modified dsRNA backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3′-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3′-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3′-5′ linkages, 2′-5′ linked analogs of these, and those) having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3′-5′ to 5′-3′ or 2′-5′ to 5′-2′. Various salts, mixed salts and free acid forms are also included.
  • Representative U.S. patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S. Pat. Nos. 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,195; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,316; 5,550,111; 5,563,253; 5,571,799; 5,587,361; and 5,625,050, each of which is herein incorporated by reference
  • Preferred modified dsRNA backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatoms and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts.
  • Representative U.S. patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S. Pat. Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,64,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and, 5,677,439, each of which is herein incorporated by reference.
  • In other preferred dsRNA mimetics, both the sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an dsRNA mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar backbone of an dsRNA is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al., Science, 1991, 254, 1497-1500.
  • Most preferred embodiments of the invention are dsRNAs with phosphorothioate backbones and oligonucleosides with heteroatom backbones, and in particular —CH2—NH—CH2—, —CH2—N(CH3)—O—CH2—[known as a methylene (methylimino) or MMI backbone], —CH2—O—N(CH3)—CH2—, —CH2—N(CH3)—N(CH3)—CH2— and —N(CH3)—CH2—CH2—[wherein the native phosphodiester backbone is represented as —O—P—O—CH2—] of the above-referenced U.S. Pat. No. 5,489,677, and the amide backbones of the above-referenced U.S. Pat. No. 5,602,240. Also preferred are dsRNAs having morpholino backbone structures of the above-referenced U.S. Pat. No. 5,034,506.
  • Modified dsRNAs may also contain one or more substituted sugar moieties. Preferred dsRNAs comprise one of the following at the 2′ position: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C1 to C10 alkyl or C2 to C10 alkenyl and alkynyl. Particularly preferred are O[(CH2)nO]mCH3, O(CH2)nOCH3, O(CH2)nNH2, O(CH2)nCH3, O(CH2)nONH2, and O(CH2)nON[(CH2)nCH3)]2, where n and m are from 1 to about 10. Other preferred dsRNAs comprise one of the following at the 2′ position: C1 to C10 lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH3, OCN, Cl, Br, CN, CF3, OCF3, SOCH3, SO2CH3, ONO2, NO2, N3, NH2, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an dsRNA, or a group for improving the pharmacodynamic properties of an dsRNA, and other substituents having similar properties. A preferred modification includes 2′-methoxyethoxy (2′-O—CH2CH2OCH3, also known as 2′-O-(2-methoxyethyl) or 2′-MOE) (Martin et al., Helv. Chim. Acta, 1995, 78, 486-504) i.e., an alkoxy-alkoxy group. A further preferred modification includes 2′-dimethylaminooxyethoxy, i.e., a O(CH2)2ON(CH3)2 group, also known as 2′-DMAOE, as described in examples herein below, and 2′-dimethylaminoethoxyethoxy (also known in the art as 2′-O-dimethylaminoethoxyethyl or 2′-DMAEOE), i.e., 2′—O—CH2—O—CH2—N(CH2)2, also described in examples herein below.
  • Other preferred modifications include 2′-methoxy (2′-OCH3), 2′-aminopropoxy (2′-OCH2CH2CH2NH2) and 2′-fluoro (2′-F). Similar modifications may also be made at other positions on the dsRNA, particularly the 3′ position of the sugar on the 3′ terminal nucleotide or in 2′-5′ linked dsRNAs and the 5′ position of 5′ terminal nucleotide. DsRNAs may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative U.S. patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat. Nos. 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; and 5,700,920, certain of which are commonly owned with the instant application, and each of which is herein incorporated by reference in its entirety.
  • DsRNAs may also include nucleobase (often referred to in the art simply as “base”) modifications or substitutions. As used herein, “unmodified” or “natural” nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl anal other 8-substituted adenines and guanines, 5-halo, particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-daazaadenine and 3-deazaguanine and 3-deazaadenine. Further nucleobases include those disclosed in U.S. Pat. No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858-859, Kroschwitz, J. L, ed. John Wiley & Sons, 1990, these disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y S., Chapter 15, DsRNA Research and Applications, pages 289-302, Crooke, S. T. and Lebleu, B., Ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2° C. (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B., Eds., DsRNA Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions, even more particularly when combined with 2′-β-methoxyethyl sugar modifications.
  • Representative U.S. patents that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include, but are not limited to, the above noted U.S. Pat. No. 3,687,808, as well as U.S. Pat. Nos. 4,845,205; 5,130,30; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121, 5,596,091; 5,614,617; and 5,681,941, each of which is herein incorporated by reference, and U.S. Pat. No. 5,750,692, also herein incorporated by reference.
  • Conjugates
  • Another modification of the dsRNAs of the invention involves chemically linking to the dsRNA one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the dsRNA. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acid. Sci. USA, 199, 86, 6553-6556), cholic acid (Manoharan et al., Biorg. Med. Chem. Let., 1994 4 1053-1060), a thioether, e.g., beryl-S-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Biorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al., EMBO J, 1991, 10, 1111-1118; Kabanov et al., FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium 1,2-di-O-hexadecyl-rac-glycero-3-Hphosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyloxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937).
  • Representative U.S. patents that teach the preparation of such dsRNA conjugates include, but are not limited to, U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941, each of which is herein incorporated by reference.
  • It is not necessary for all positions in a given compound to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an dsRNA. The present invention also includes dsRNA compounds which are chimeric compounds. “Chimeric” dsRNA compounds or “chimeras,” in the context of this invention, are dsRNA compounds, particularly dsRNAs, which contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nucleotide in the case of an dsRNA compound. These dsRNAs typically contain at least one region wherein the dsRNA is modified so as to confer upon the dsRNA increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid. An additional region of the dsRNA may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNase H is a cellular endonuclease which cleaves the RNA strand of an RNA:DNAduplex. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby greatly enhancing the efficiency of dsRNA inhibition of gene expression. Consequently, comparable results can often be obtained with shorter dsRNAs when chimeric dsRNAs are used, compared to phosphorothioate deoxy dsRNAs hybridizing to the same target region. Cleavage of the RNA target can be routinely detected by gel electrophoresis and, if necessary, associated nucleic acid hybridization techniques known in the art.
  • In certain instances, the dsRNA may be modified by a non-ligand group. A number of non-ligand molecules have been conjugated to dsRNAs in order to enhance the activity, cellular distribution or cellular uptake of the dsRNA, and procedures for performing such conjugations are available in the scientific literature. Such non-ligand moieties have included lipid moieties, such as cholesterol (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86:6553), cholic acid (Manoharan et al., Bioorg. Med. Chem. Lett., 1994, 4:1053), a thioether, e.g., hexyl-5-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660:306; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3:2765), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20:533), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al., EMBO J., 1991, 10:111; Kabanov et al., FEBS Lett., 1990, 259:327; Svinarchuk et al., Biochimie, 1993, 75:49), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1,2-di-O-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36:3651; Shea et al., Nucl. Acids Res., 1990, 18:3777), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14:969), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36:3651), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264:229), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277:923). Representative United States patents that teach the preparation of such dsRNA conjugates have been listed above. Typical conjugation protocols involve the synthesis of dsRNAs bearing an aminolinker at one or more positions of the sequence. The amino group is then reacted with the molecule being conjugated using appropriate coupling or activating reagents. The conjugation reaction may be performed either with the dsRNA still bound to the solid support or following cleavage of the dsRNA in solution phase. Purification of the dsRNA conjugate by HPLC typically affords the pure conjugate.
  • Vector Encoded siRNA Agents
  • In another aspect of the invention, GSK-3 specific dsRNA molecules that are expressed from transcription units inserted into DNA or RNA vectors (see, e.g., Couture, A, et al., TIG. (1996), 12:5-10; Skillern, A., et al., International PCT Publication No. WO 00/22113, Conrad, International PCT Publication No. WO 00/22114, and Conrad, U.S. Pat. No. 6,054,299). These transgenes can be introduced as a linear construct, a circular plasmid, or a viral vector, which can be incorporated and inherited as a transgene integrated into the host genome. The transgene can also be constructed to permit it to be inherited as an extrachromosomal plasmid (Gassmann, et al., Proc. Natl. Acad. Sci. USA (1995) 92:1292).
  • The individual strands of a dsRNA can be transcribed by promoters on two separate expression vectors and co-transfected into a target cell. Alternatively each individual strand of the dsRNA can be transcribed by promoters both of which are located on the same expression plasmid. In a preferred embodiment, a dsRNA is expressed as an inverted repeat joined by a linker polynucleotide sequence such that the dsRNA has a stem and loop structure.
  • The recombinant dsRNA expression vectors are generally DNA plasmids or viral vectors. dsRNA expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus (for a review, see Muzyczka, et al., Curr. Topics Micro. Immunol. (1992) 158:97-129)); adenovirus (see, for example, Berkner, et al., BioTechniques (1998) 6:616), Rosenfeld et al. (1991, Science 252:431-434), and Rosenfeld et al. (1992), Cell 68:143-155)); or alphavirus as well as others known in the art. Retroviruses have been used to introduce a variety of genes into many different cell types, including epithelial cells, in vitro and/or in vivo (see, e.g., Eglitis, et al., Science (1985) 230:1395-1398; Danos and Mulligan, Proc. Natl. Acad. Sci. USA (1998) 85:6460-6464; Wilson et al., 1988, Proc. Natl. Acad. Sci. USA 85:3014-3018; Armentano et al., 1990, Proc. Natl. Acad. Sci. USA 87:61416145; Huber et al., 1991, Proc. Natl. Acad. Sci. USA 88:8039-8043; Ferry et al., 1991, Proc. Natl. Acad. Sci. USA 88:8377-8381; Chowdhury et al., 1991, Science 254:1802-1805; van Beusechem. et al., 1992, Proc. Nad. Acad. Sci. USA 89:7640-19; Kay et al., 1992, Human Gene Therapy 3:641-647; Dai et al., 1992, Proc. Natl. Acad. Sci. USA 89:10892-10895; Hwu et al., 1993, J. Immunol. 150:4104-4115; U.S. Pat. No. 4,868,116; U.S. Pat. No. 4,980,286; PCT Application WO 89/07136; PCT Application WO 89/02468; PCT Application WO 89/05345; and PCT Application WO 92/07573). Recombinant retroviral vectors capable of transducing and expressing genes inserted into the genome of a cell can be produced by transfecting the recombinant retroviral genome into suitable packaging cell lines such as PA317 and Psi-CRIP (Comette et al., 1991, Human Gene Therapy 2:5-10; Cone et al., 1984, Proc. Natl. Acad. Sci. USA 81:6349). Recombinant adenoviral vectors can be used to infect a wide variety of cells and tissues in susceptible hosts (e.g., rat, hamster, dog, and chimpanzee) (Hsu et al., 1992, J. Infectious Disease, 166:769), and also have the advantage of not requiring mitotically active cells for infection.
  • Any viral vector capable of accepting the coding sequences for the dsRNA molecule(s) to be expressed can be used, for example vectors derived from adenovirus (AV); adeno-associated virus (AAV); retroviruses (e.g., lentiviruses (LV), Rhabdoviruses, murine leukemia virus); herpes virus, and the like. The tropism of viral vectors can be modified by pseudotyping the vectors with envelope proteins or other surface antigens from other viruses, or by substituting different viral capsid proteins, as appropriate.
  • For example, lentiviral vectors of the invention can be pseudotyped with surface proteins from vesicular stomatitis virus (VSV), rabies, Ebola, Mokola, and the like. AAV vectors of the invention can be made to target different cells by engineering the vectors to express different capsid protein serotypes. For example, an AAV vector expressing a serotype 2 capsid on a serotype 2 genome is called AAV 2/2. This serotype 2 capsid gene in the AAV 2/2 vector can be replaced by a serotype 5 capsid gene to produce an AAV 2/5 vector. Techniques for constructing AAV vectors which express different capsid protein serotypes are within the skill in the art; see, e.g., Rabinowitz J E et al. (2002), J Virol 76:791-801, the entire disclosure of which is herein incorporated by reference.
  • Selection of recombinant viral vectors suitable for use in the invention, methods for inserting nucleic acid sequences for expressing the dsRNA into the vector, and methods of delivering the viral vector to the cells of interest are within the skill in the art. See, for example, Dornburg R (1995), Gene Therap. 2: 301-310; Eglitis M A (1988), Biotechniques 6: 608-614; Miller A D (1990), Hum Gene Therap. 1: 5-14; Anderson W F (1998), Nature 392: 25-30; and Rubinson D A et al., Nat. Genet. 33: 401-406, the entire disclosures of which are herein incorporated by reference.
  • Preferred viral vectors are those derived from AV and AAV. In a particularly preferred embodiment, the dsRNA of the invention is expressed as two separate, complementary single-stranded RNA molecules from a recombinant AAV vector having, for example, either the U6 or H1 RNA promoters, or the cytomegalovirus (CMV) promoter.
  • A suitable AV vector for expressing the dsRNA of the invention, a method for constructing the recombinant AV vector, and a method for delivering the vector into target cells, are described in Xia H et al. (2002), Nat. Biotech. 20: 1006-1010.
  • Suitable AAV vectors for expressing the dsRNA of the invention, methods for constructing the recombinant AV vector, and methods for delivering the vectors into target cells are described in Samulski Ret al. (1987), J. Virol. 61: 3096-3101; Fisher K Jet al. (1996), J. Virol, 70: 520-532; Samulski R et al. (1989), J. Virol. 63: 3822-3826; U.S. Pat. No. 5,252,479; U.S. Pat. No. 5,139,941; International Patent Application No. WO 94/13788; and International Patent Application No. WO 93/24641, the entire disclosures of which are herein incorporated by reference.
  • The promoter driving dsRNA expression in either a DNA plasmid or viral vector of the invention may be a eukaryotic RNA polymerase I (e.g. ribosomal RNA promoter), RNA polymerase II (e.g. CMV early promoter or actin promoter or Ul snRNA promoter) or generally RNA polymerase III promoter (e.g. U6 snRNA or 7SK RNA promoter) or a prokaryotic promoter, for example the T7 promoter, provided the expression plasmid also encodes T7 RNA polymerase required for transcription from a T7 promoter. The promoter can also direct transgene expression to the pancreas (see, e.g., the insulin regulatory sequence for pancreas (Bucchini et al., 1986, Proc. Natl. Acad. Sci. USA 83:2511-2515)).
  • In addition, expression of the transgene can be precisely regulated, for example, by using an inducible regulatory sequence and expression systems such as a regulatory sequence that is sensitive to certain physiological regulators, e.g., circulating glucose levels, or hormones (Docherty et al., 1994, FASEB J. 8:20-24). Such inducible expression systems, suitable for the control of transgene expression in cells or in mammals include regulation by ecdysone, by estrogen, progesterone, tetracycline, chemical inducers of dimerization, and isopropyl-beta-D1-thiogalactopyranoside (EPTG). A person skilled in the art would be able to choose the appropriate regulatory/promoter sequence based on the intended use of the dsRNA transgene.
  • Generally, recombinant vectors capable of expressing dsRNA molecules are delivered as described below, and persist in target cells. Alternatively, viral vectors can be used that provide for transient expression of dsRNA molecules. Such vectors can be repeatedly administered as necessary. Once expressed, the dsRNAs bind to target RNA and modulate its function or expression. Delivery of dsRNA expressing vectors can be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that allows for introduction into a desired target cell.
  • dsRNA expression DNA plasmids are typically transfected into target cells as a complex with cationic lipid carriers (e.g. Oligofectamine) or non-cationic lipid-based carriers (e.g. Transit-TKO™). Multiple lipid transfections for dsRNA-mediated knockdowns targeting different regions of a single GSK-3 gene or two GSK-3 genes over a period of a week or more are also contemplated by the invention. Successful introduction of the vectors of the invention into host cells can be monitored using various known methods. For example, transient transfection. can be signaled with a reporter, such as a fluorescent marker, such as Green Fluorescent Protein (GFP). Stable transfection of ex vivo cells can be ensured using markers that provide the transfected cell with resistance to specific environmental factors (e.g., antibiotics and drugs), such as hygromycin B resistance.
  • The GSK-3 specific dsRNA molecules can also be inserted into vectors and used as gene therapy vectors for human patients. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see U.S. Pat. No. 5,328,470) or by stereotactic injection (see e.g., Chen et al. (1994) Proc. Natl. Acad. Sci. USA 91:3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can include a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells which produce the gene delivery system.
  • III. PHARMACEUTICAL COMPOSITIONS COMPRISING dsRNA
  • In one embodiment, the invention provides pharmaceutical compositions comprising a dsRNA, as described herein, and a pharmaceutically acceptable carrier. The pharmaceutical composition comprising the dsRNA is useful for treating a disease or disorder associated with the expression or activity of a GSK-3 gene, such as pathological processes mediated by GSK-3 expression. Such pharmaceutical compositions are formulated based on the mode of delivery. One example is compositions that are formulated for systemic administration via parenteral delivery.
  • The pharmaceutical compositions featured herein are administered in dosages sufficient to inhibit expression of a GSK-3 gene. In general, a suitable dose of dsRNA will be in the range of 0.01 to 200.0 milligrams per kilogram body weight of the recipient per day, generally in the range of 1 to 50 mg per kilogram body weight per day. For example, the dsRNA can be administered at 0.01 mg/kg, 0.05 mg/kg, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 3 mg/kg, 5.0 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg, 40 mg/kg, or 50 mg/kg per single dose.
  • The pharmaceutical composition may be administered once daily or the dsRNA may be administered as two, three, or more sub-doses at appropriate intervals throughout the day or even using continuous infusion or delivery through a controlled release formulation. In that case, the dsRNA contained in each sub-dose must be correspondingly smaller in order to achieve the total daily dosage. The dosage unit can also be compounded for delivery over several days, e.g., using a conventional sustained release formulation which provides sustained release of the dsRNA over a several day period. Sustained release formulations are well known in the art and are particularly useful for delivery of agents at a particular site, such as could be used with the agents of the present invention. In this embodiment, the dosage unit contains a corresponding multiple of the daily dose.
  • The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a composition can include a single treatment or a series of treatments. Estimates of effective dosages and in vivo half-lives for the individual dsRNAs encompassed by the invention can be made using conventional methodologies or on the basis of in vivo testing using an appropriate animal model, as described elsewhere herein.
  • Advances in mouse genetics have generated a number of mouse models for the study of various human diseases, such as pathological processes mediated by GSK-3 expression. Such models are used for in vivo testing of dsRNA, as well as for determining a therapeutically effective dose.
  • The data obtained from cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of compositions featured in the invention lies generally within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the methods featured in the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range of the compound or, when appropriate, of the polypeptide product of a target sequence (e.g., achieving a decreased concentration of the polypeptide) that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.
  • The dsRNAs featured in the invention can be administered in combination with other known agents effective in treatment of pathological processes mediated by target gene expression. In any event, the administering physician can adjust the amount and timing of dsRNA administration on the basis of results observed using standard measures of efficacy known in the art or described herein.
  • Administration
  • The present invention also includes pharmaceutical compositions and formulations which include the dsRNA compounds of the invention. The pharmaceutical compositions of the present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical, pulmonary, e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. In one embodiment, the pharmaceutical composition is administered intracranially, directly into the nucleus accumbens.
  • Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Coated condoms, gloves and the like may also be useful. Preferred topical formulations include those in which the dsRNAs of the invention are in admixture with a topical delivery agent such as lipids, liposomes, fatty acids, fatty acid esters, steroids, chelating agents and surfactants. Preferred lipids and liposomes include neutral (e.g. dioleoylphosphatidyl DOPE ethanolamine, dimyristoylphosphatidyl choline DMPC, distearolyphosphatidyl choline) negative (e.g. dimyristoylphosphatidyl glycerol DMPG) and cationic (e.g. dioleoyltetramethylaminopropyl DOTAP and dioleoylphosphatidyl ethanolamine DOTMA). DsRNAs of the invention may be encapsulated within liposomes or may form complexes thereto, in particular to cationic liposomes. Alternatively, dsRNAs may be complexed to lipids, in particular to cationic lipids. Preferred fatty acids and esters include but are not limited arachidonic acid, oleic acid, eicosanoic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a C1-10 alkyl ester (e.g. isopropylmyristate IPM), monoglyceride, diglyceride or pharmaceutically acceptable salt thereof. Topical formulations are described in detail in U.S. patent application Ser. No. 09/315,298 filed on May 20, 1999 which is incorporated herein by reference in its entirety.
  • Compositions and formulations for oral administration include powders or granules, microparticulates, nanoparticulates, suspensions or solutions in water or non-aqueous media, capsules, gel capsules, sachets, tablets or minitablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable. Preferred oral formulations are those in which dsRNAs of the invention are administered in conjunction with one or more penetration enhancers surfactants and chelators. Preferred surfactants include fatty acids and/or esters or salts thereof, bile acids and/or salts thereof. Preferred bile acids/salts include chenodeoxycholic acid (CDCA) and ursodeoxychenodeoxycholic acid (UDCA), cholic acid, dehydrocholic acid, deoxycholic acid, glucholic acid, glycholic acid, glycodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, sodium tauro-24,25-dihydro-fusidate and sodium glycodihydrofusidate. Preferred fatty acids include arachidonic acid, undecanoic acid, oleic acid, lauric acid, caprylic acid, capric acid, myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein, dilaurin, glyceryl 1-monocaprate, 1-dodecylazacycloheptan-2-one, an acylcarnitine, an acylcholine, or a monoglyceride, a diglyceride or a pharmaceutically acceptable salt thereof (e.g. sodium). Also preferred are combinations of penetration enhancers, for example, fatty acids/salts in combination with bile acids/salts. A particularly preferred combination is the sodium salt of lauric acid, capric acid and UDCA. Further penetration enhancers include polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether. DsRNAs of the invention may be delivered orally, in granular form including sprayed dried particles, or complexed to form micro or nanoparticles. DsRNA complexing agents include poly-amino acids; polyimines; polyacrylates; polyalkylacrylates, polyoxethanes, polyalkylcyanoacrylates; cationized gelatins, albumins, starches, acrylates, polyethyleneglycols (PEG) and starches; polyalkylcyanoacrylates; DEAE-derivatized polyimines, pollulans, celluloses and starches. Particularly preferred complexing agents include chitosan, N-trimethylchitosan, poly-L-lysine, polyhistidine, polyornithine, polyspermines, protamine, polyvinylpyridine, polythiodiethylaminomethylethylene P(TDAE), polyaminostyrene (e.g. p-amino), poly(methylcyanoacrylate), poly(ethylcyanoacrylate), poly(butylcyanoacrylate), poly(isobutylcyanoacrylate), poly(isohexylcynaoacrylate), DEAE-methacrylate, DEAE-hexylacrylate, DEAE-acrylamide, DEAE-albumin and DEAE-dextran, polymethylacrylate, polyhexylacrylate, poly(D,L-lactic acid), poly(DL-lactic-co-glycolic acid (PLGA), alginate, and polyethyleneglycol (PEG). Oral formulations for dsRNAs and their preparation are described in detail in U.S. application. Ser. No. 08/886,829 (filed Jul. 1, 1997), Ser. No. 09/108,673 (filed Jul. 1, 1998), Ser. No. 09/256,515 (filed Feb. 23, 1999), Ser. No. 09/082,624 (filed May 21, 1998) and Ser. No. 09/315,298 (filed May 20, 1999), each of which is incorporated herein by reference in their entirety.
  • Compositions and formulations for parenteral, intrathecal, intraventricular or intrahepatic administration may include sterile aqueous solutions which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients.
  • Pharmaceutical compositions of the present invention include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids. Particularly preferred are formulations that target the liver when treating hepatic disorders such as hepatic carcinoma.
  • The pharmaceutical formulations of the present invention, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.
  • The compositions of the present invention may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, gel capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.
  • Emulsions
  • The compositions of the present invention may be prepared and formulated as emulsions. Emulsions are typically heterogenous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1 μm in diameter (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1, p. 245; Block in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335; Higuchi et al., in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 301). Emulsions are often biphasic systems comprising two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be of either the water-in-oil (w/o) or the oil-in-water (o/w) variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase, the resulting composition is called a water-in-oil (w/o) emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase, the resulting composition is called an oil-in-water (o/w) emulsion. Emulsions may contain additional components in addition to the dispersed phases, and the active drug which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase. Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil-in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) emulsions. Such complex formulations often provide certain advantages that simple binary emulsions do not. Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion. Likewise a system of oil droplets enclosed in globules of water stabilized in an oily continuous phase provides an o/w/o emulsion.
  • Emulsions are characterized by little or no thermodynamic stability. Often, the dispersed or discontinuous phase of the emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity of the formulation. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incorporated into either phase of the emulsion. Emulsifiers may broadly be classified into four categories: synthetic surfactants, naturally occurring emulsifiers, absorption bases, and finely dispersed solids (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).
  • Synthetic surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion. The ratio of the hydrophilic to the hydrophobic nature of the surfactant has been termed the hydrophile/lipophile balance (HLB) and is a valuable tool in categorizing and selecting surfactants in the preparation of formulations. Surfactants may be classified into different classes based on the nature of the hydrophilic group: nonionic, anionic, cationic and amphoteric (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285).
  • Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia. Absorption bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations. These include polar inorganic solids, such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate.
  • A large variety of non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives and antioxidants (Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).
  • Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed-phase droplets and by increasing the viscosity of the external phase.
  • Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides that may readily support the growth of microbes, these formulations often incorporate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid. Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.
  • The application of emulsion formulations via dermatological, oral and parenteral routes and methods for their manufacture have been reviewed in the literature (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Emulsion formulations for oral delivery have been very widely used because of ease of formulation, as well as efficacy from an absorption and bioavailability standpoint (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Mineral-oil base laxatives, oil-soluble vitamins and high fat nutritive preparations are among the materials that have commonly been administered orally as o/w emulsions.
  • In one embodiment of the present invention, the compositions of dsRNAs and nucleic acids are formulated as microemulsions. A microemulsion may be defined as a system of water, oil and amphiphile which is a single optically isotropic and thermodynamically stable liquid solution (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Typically microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain-length alcohol to form a transparent system. Therefore, microemulsions have also been described as thermodynamically stable, isotropically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in: Controlled Release of Drugs: Polymers and Aggregate Systems, Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 185-215). Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte. Whether the microemulsion is of the water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties of the oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, p. 271).
  • The phenomenological approach utilizing phase diagrams has been extensively studied and has yielded a comprehensive knowledge, to one skilled in the art, of how to formulate microemulsions (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335). Compared to conventional emulsions, microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously.
  • Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (SO750), decaglycerol decaoleate (DA0750), alone or in combination with cosurfactants. The cosurfactant, usually a short-chain alcohol such as ethanol, 1-propanol, and 1-butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because of the void space generated among surfactant molecules. Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art. The aqueous phase may typically be, but is not limited to, water, an aqueous solution of the drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol. The oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and tri-glycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil.
  • Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absorption of drugs. Lipid based microemulsions (both o/w and w/o) have been proposed to enhance the oral bioavailability of drugs, including peptides (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385-1390; Ritschel, Meth. Find. Exp. Clin. Pharmacol., 1993, 13, 205). Microemulsions afford advantages of improved drug solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absorption due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (Constantinides et al., Pharmaceutical Research, 1994, 11, 1385; Ho et al., J. Pharm. Sci., 1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or dsRNAs. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications. It is expected that the microemulsion compositions and formulations of the present invention will facilitate the increased systemic absorption of dsRNAs and nucleic acids from the gastrointestinal tract, as well as improve the local cellular uptake of dsRNAs and nucleic acids.
  • Microemulsions of the present invention may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties of the formulation and to enhance the absorption of the dsRNAs and nucleic acids of the present invention. Penetration enhancers used in the microemulsions of the present invention may be classified as belonging to one of five broad categories—surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of these classes has been discussed above.
  • Liposomal Formulations
  • There are many organized surfactant structures besides microemulsions that have been studied and used for the formulation of drugs. These include monolayers, micelles, bilayers and vesicles. Vesicles, such as liposomes, have attracted great interest because of their specificity and the duration of action they offer from the standpoint of drug delivery. As used in the present invention, the term “liposome” means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers.
  • Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Non-cationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo.
  • In order to cross intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a liposome which is highly deformable and able to pass through such fine pores.
  • Further advantages of liposomes include; liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incorporate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Important considerations in the preparation of liposome formulations are the lipid surface charge, vesicle size and the aqueous volume of the liposomes.
  • Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes and as the merging of the liposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act.
  • Liposomal formulations have been the focus of extensive investigation as the mode of delivery for many drugs. There is growing evidence that for topical administration, liposomes present several advantages over other formulations. Such advantages include reduced side-effects related to high systemic absorption of the administered drug, increased accumulation of the administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin.
  • Several reports have detailed the ability of liposomes to deliver agents including high-molecular weight DNA into the skin. Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting of the upper epidermis
  • Liposomes fall into two broad classes. Cationic liposomes are positively charged liposomes which interact with the negatively charged DNA molecules to form a stable complex. The positively charged DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al., Biochem. Biophys. Res. Commun., 1987, 147, 980-985).
  • Liposomes which are pH-sensitive or negatively-charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression of the exogenous gene was detected in the target cells (Zhou et al., Journal of Controlled Release, 1992, 19, 269-274).
  • One major type of liposomal composition includes phospholipids other than naturally-derived phosphatidylcholine. Neutral liposome compositions, for example, can be formed from dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC). Anionic liposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE). Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC. Another type is formed from mixtures of phospholipid and/or phosphatidylcholine and/or cholesterol.
  • Several studies have assessed the topical delivery of liposomal drug formulations to the skin. Application of liposomes containing interferon to guinea pig skin resulted in a reduction of skin herpes sores while delivery of interferon via other means (e.g., as a solution or as an emulsion) were ineffective (Weiner et al., Journal of Drug Targeting, 1992, 2, 405-410). Further, an additional study tested the efficacy of interferon administered as part of a liposomal formulation to the administration of interferon using an aqueous system, and concluded that the liposomal formulation was superior to aqueous administration (du Plessis et al., Antiviral Research, 1992, 18, 259-265).
  • Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol. Non-ionic liposomal formulations comprising Novasome™ I (glyceryl dilaurate/cholesterol/po-lyoxyethylene-10-stearyl ether) and Novasome™ II (glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers of the skin (Hu et al. S.T.P.Pharma. Sci., 1994, 4, 6, 466).
  • Liposomes also include “sterically stabilized” liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incorporated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking such specialized lipids. Examples of sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the liposome (A) comprises one or more glycolipids, such as monosialoganglioside GM1, or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. While not wishing to be bound by any particular theory, it is thought in the art that, at least for sterically stabilized liposomes containing gangliosides, sphingomyelin, or PEG-derivatized lipids, the enhanced circulation half-life of these sterically stabilized liposomes derives from a reduced uptake into cells of the reticuloendothelial system (RES) (Allen et al., FEBS Letters, 1987, 223, 42; Wu et al., Cancer Research, 1993, 53, 3765).
  • Various liposomes comprising one or more glycolipids are known in the art. Papahadjopoulos et al. (Ann. N.Y. Acad. Sci., 1987, 507, 64) reported the ability of monosialoganglioside GM1, galactocerebroside sulfate and phosphatidylinositol to improve blood half-lives of liposomes. These findings were expounded upon by Gabizon et al. (Proc. Natl. Acad. Sci. U.S.A., 1988, 85, 6949). U.S. Pat. No. 4,837,028 and WO 88/04924, both to Allen et al., disclose liposomes comprising (1) sphingomyelin and (2) the ganglioside GM1 or a galactocerebroside sulfate ester. U.S. Pat. No. 5,543,152 (Webb et al.) discloses liposomes comprising sphingomyelin. Liposomes comprising 1,2-sn-dimyristoylphosphat-idylcholine are disclosed in WO 97/13499 (Lim et al).
  • Many liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art. Sunamoto et al. (Bull. Chem. Soc. Jpn., 1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C1215G, that contains a PEG moiety. Illum et al. (FEBS Lett., 1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives. Synthetic phospholipids modified by the attachment of carboxylic groups of polyalkylene glycols (e.g., PEG) are described by Sears (U.S. Pat. Nos. 4,426,330 and 4,534,899). Klibanov et al. (FEBS Lett., 1990, 268, 235) described experiments demonstrating that liposomes comprising phosphatidylethanolamine (PE) derivatized with PEG or PEG stearate have significant increases in blood circulation half-lives. Blume et al. (Biochimica et Biophysica Acta, 1990, 1029, 91) extended such observations to other PEG-derivatized phospholipids, e.g., DSPE-PEG, formed from the combination of distearoylphosphatidylethanolamine (DSPE) and PEG. Liposomes having covalently bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 B1 and WO 90/04384 to Fisher. Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Pat. Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Pat. No. 5,213,804 and European Patent No. EP 0 496 813 B1). Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Pat. No. 5,225,212 (both to Martin et al.) and in WO 94/20073 (Zalipsky et al.) Liposomes comprising PEG-modified ceramide lipids are described in WO 96/10391 (Choi et al). U.S. Pat. No. 5,540,935 (Miyazaki et al.) and U.S. Pat. No. 5,556,948 (Tagawa et al.) describe PEG-containing liposomes that can be further derivatized with functional moieties on their surfaces.
  • A number of liposomes comprising nucleic acids are known in the art. WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes. U.S. Pat. No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include a dsRNA. U.S. Pat. No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love et al. discloses liposomes comprising dsRNAs targeted to the raf gene.
  • Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets which are so highly deformable that they are easily able to penetrate through pores which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g., they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin.
  • Surfactants find wide application in formulations such as emulsions (including microemulsions) and liposomes. The most common way of classifying and ranking the properties of the many different types of surfactants, both natural and synthetic, is by the use of the hydrophile/lipophile balance (HLB). The nature of the hydrophilic group (also known as the “head”) provides the most useful means for categorizing the different surfactants used in formulations (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).
  • If the surfactant molecule is not ionized, it is classified as a nonionic surfactant. Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general their HLB values range from 2 to about 18 depending on their structure. Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters. Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class. The polyoxyethylene surfactants are the most popular members of the nonionic surfactant class.
  • If the surfactant molecule carries a negative charge when it is dissolved or dispersed in water, the surfactant is classified as anionic. Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates. The most important members of the anionic surfactant class are the alkyl sulfates and the soaps.
  • If the surfactant molecule carries a positive charge when it is dissolved or dispersed in water, the surfactant is classified as cationic. Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class.
  • If the surfactant molecule has the ability to carry either a positive or negative charge, the surfactant is classified as amphoteric. Amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N-alkylbetaines and phosphatides.
  • The use of surfactants in drug products, formulations and in emulsions has been reviewed (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, N.Y., 1988, p. 285).
  • Nucleic Acid Lipid Particles
  • In one embodiment, a dsRNA featured in the invention is fully encapsulated in the lipid formulation to form a SPLP, pSPLP, SNALP, or other nucleic acid-lipid particle. As used herein, the term “SNALP” refers to a stable nucleic acid-lipid particle, including SPLP. As used herein, the term “SPLP” refers to a nucleic acid-lipid particle comprising plasmid DNA encapsulated within a lipid vesicle. SNALPs and SPLPs typically contain a cationic lipid, a non-cationic lipid, and a lipid that prevents aggregation of the particle (e.g., a PEG-lipid conjugate). SNALPs and SPLPs are extremely useful for systemic applications, as they exhibit extended circulation lifetimes following intravenous (i.v.) injection and accumulate at distal sites (e.g., sites physically separated from the administration site). SPLPs include “pSPLP,” which include an encapsulated condensing agent-nucleic acid complex as set forth in PCT Publication No. WO 00/03683. The particles of the present invention typically have a mean diameter of about 50 nm to about 150 nm, more typically about 60 nm to about 130 nm, more typically about 70 nm to about 110 nm, most typically about 70 to about 90 nm, and are substantially nontoxic. In addition, the nucleic acids when present in the nucleic acid-lipid particles of the present invention are resistant in aqueous solution to degradation with a nuclease. Nucleic acid-lipid particles and their method of preparation are disclosed in, e.g., U.S. Pat. Nos. 5,976,567; 5,981,501; 6,534,484; 6,586,410; 6,815,432; and PCT Publication No. WO 96/40964.
  • In one embodiment, the lipid to drug ratio (mass/mass ratio) (e.g., lipid to dsRNA ratio) will be in the range of from about 1:1 to about 50:1, from about 1:1 to about 25:1, from about 3:1 to about 15:1, from about 4:1 to about 10:1, from about 5:1 to about 9:1, or about 6:1 to about 9:1.
  • The cationic lipid may be, for example, N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP), N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA), N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA), 1,2-DiLinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA), 1,2-Dilinoleylcarbamoyloxy-3-dimethylaminopropane (DLin-C-DAP), 1,2-Dilinoleyoxy-3-(dimethylamino)acetoxypropane (DLin-DAC), 1,2-Dilinoleyoxy-3-morpholinopropane (DLin-MA), 1,2-Dilinoleoyl-3-dimethylaminopropane (DLinDAP), 1,2-Dilinoleylthio-3-dimethylaminopropane (DLin-S-DMA), 1-Linoleoyl-2-linoleyloxy-3-dimethylaminopropane (DLin-2-DMAP), 1,2-Dilinoleyloxy-3-trimethylaminopropane chloride salt (DLin-TMA.Cl), 1,2-Dilinoleoyl-3-trimethylaminopropane chloride salt (DLin-TAP.Cl), 1,2-Dilinoleyloxy-3-(N-methylpiperazino)propane (DLin-MPZ), or 3-(N,N-Dilinoleylamino)-1,2-propanediol (DLinAP), 3-(N,N-Dioleylamino)-1,2-propanedio (DOAP), 1,2-Dilinoleyloxo-3-(2-N,N-dimethylamino)ethoxypropane (DLin-EG-DMA), 2,2-Dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA) or analogs thereof, or a mixture thereof. The cationic lipid may comprise from about 20 mol % to about 50 mol % or about 40 mol % of the total lipid present in the particle.
  • In another embodiment, the compound 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane can be used to prepare lipid-siRNA nanoparticles. Synthesis of 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane is described in U.S. provisional patent application No. 61/107,998 filed on Oct. 23, 2008, which is herein incorporated by reference.
  • In one embodiment, the lipid-siRNA particle includes 40% 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane: 10% DSPC: 40% Cholesterol: 10% PEG-C-DOMG (mole percent) with a particle size of 63.0±20 nm and a 0.027 siRNA/Lipid Ratio.
  • The non-cationic lipid may be an anionic lipid or a neutral lipid including, but not limited to, distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoyl-phosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phosphatidyl-ethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, 1-stearoyl-2-oleoyl-phosphatidyethanolamine (SOPE), cholesterol, or a mixture thereof. The non-cationic lipid may be from about 5 mol % to about 90 mol %, about 10 mol %, or about 58 mol % if cholesterol is included, of the total lipid present in the particle.
  • The conjugated lipid that inhibits aggregation of particles may be, for example, a polyethyleneglycol (PEG)-lipid including, without limitation, a PEG-diacylglycerol (DAG), a PEG-dialkyloxypropyl (DAA), a PEG-phospholipid, a PEG-ceramide (Cer), or a mixture thereof. The PEG-DAA conjugate may be, for example, a PEG-dilauryloxypropyl (Ci2), a PEG-dimyristyloxypropyl (Ci4), a PEG-dipalmityloxypropyl (Ci6), or a PEG-distearyloxypropyl (C]8). The conjugated lipid that prevents aggregation of particles may be from 0 mol % to about 20 mol % or about 2 mol % of the total lipid present in the particle.
  • In some embodiments, the nucleic acid-lipid particle further includes cholesterol at, e.g., about 10 mol % to about 60 mol % or about 48 mol % of the total lipid present in the particle.
  • LNP01
  • In one embodiment, the lipidoid ND98.4HCl (MW 1487) (Formula I), Cholesterol (Sigma-Aldrich), and PEG-Ceramide C16 (Avanti Polar Lipids) can be used to prepare lipid-siRNA nanoparticles (i.e., LNP01 particles). Stock solutions of each in ethanol can be prepared as follows: ND98, 133 mg/ml; Cholesterol, 25 mg/ml, PEG-Ceramide C16, 100 mg/ml. The ND98, Cholesterol, and PEG-Ceramide C16 stock solutions can then be combined in a, e.g., 42:48:10 molar ratio. The combined lipid solution can be mixed with aqueous siRNA (e.g., in sodium acetate pH 5) such that the final ethanol concentration is about 35-45% and the final sodium acetate concentration is about 100-300 mM. Lipid-siRNA nanoparticles typically form spontaneously upon mixing. Depending on the desired particle size distribution, the resultant nanoparticle mixture can be extruded through a polycarbonate membrane (e.g., 100 nm cut-off) using, for example, a thermobarrel extruder, such as Lipex Extruder (Northern Lipids, Inc). In some cases, the extrusion step can be omitted. Ethanol removal and simultaneous buffer exchange can be accomplished by, for example, dialysis or tangential flow filtration. Buffer can be exchanged with, for example, phosphate buffered saline (PBS) at about pH 7, e.g., about pH 6.9, about pH 7.0, about pH 7.1, about pH 7.2, about pH 7.3, or about pH 7.4.
  • Figure US20110184046A1-20110728-C00001
  • LNP01 formulations are described, e.g., in International Application Publication No. WO 2008/042973, which is hereby incorporated by reference.
  • As mentioned above, the lipid-dsRNA particle can comprise a cationic lipid, a neutral lipid, a steroid, and optionally a lipid that prevents aggregation of the particle. The relative percentages of these constitutents can vary depending on the type of lipids used. However, in general, the cationic lipid comprises from about 20 mol % to about 70 mol % or about 40 mol % to about 60 mol % of the total lipid present in the particle; neutral lipids comprise from about 5 mol % to about 90 mol %, about 10 mol %, or about 58 mol % if cholesterol is included, of the total lipid present in the particle; the steroid (typically cholesterol) can comprise from about 10 mol % to about 60 mol % or about 48 mol % of the total lipid present in the particle; finally, the lipid that prevents aggregation of the particle, typically a conjugated lipid (e.g., a PEG-conjugated lipid) can comprise from 0 mol % to about 20 mol % or about 2 mol % of the total lipid present in the particle.
  • In one embodiment, the lipid-dsRNA particle includes 40 mol % 2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane, 10 mol % 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 40 mol % Cholesterol, 10 mol % PEG-C-DOMG with a particle size of 63.0±20 nm and a 0.027 dsRNA/Lipid Ratio.
  • In another embodiment, the lipid-dsRNA particle includes 40 mol % 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 10 mol % 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 2 mol % 3-N—[(qmethoxypoly(ethylene glycol)2000)carbamoyl]-1,2-dimyristyloxy-propylamine (PEG-C-DMA), and 48 mol % cholesterol.
  • In another embodiment, the lipid-dsRNA particle includes 57.1 mol % 1,2-Dilinolenyloxy-N,N-dimethylaminopropane (DLinDMA), 7.1 mol % DPPC, 34.4 mol % Cholesterol, 1.4 mol % PEG-cDMA.
  • In another embodiment, the lipid-dsRNA particle includes 48 mol % cholesterol, 20 mol % of the neutral lipid 1,2-distearoyl-sn-glycero-3-phosphocholine, 2 mol % of PEG-cDMA (3-N-[(methoxy poly(ethylene glycol)2000)carbamoyl]-1,2-dimyrestyloxypropylamine), and 30 mol % of the cationic lipid DLinDMA (1,2-dilinoleyloxy-3-(N,N-dimethyl)aminopropane).
  • In another embodiment, the lipid-dsRNA particle includes 48 mol % cholesterol, 20 mol % of the neutral lipid 1,2-distearoyl-sn-glycero-3-phosphocholine, 2 mol % of PEG-cDMA (3-N-[(methoxy poly(ethylene glycol)2000)carbamoyl]-1,2-dimyrestyloxypropylamine), and 30 mol % of the cationic lipid 2,2-Dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane.
  • Additional exemplary lipid-siRNA formulations are as follows:
  • cationic lipid/non-cationic
    lipid//choleseterol/PEG-lipid conjugate
    Cationic Lipid Lipid:siRNA ratio Process
    LNP05 2,2-Dilinoleyl-4- XTC/DSPC/Cholesterol/PEG-DMG Extrusion
    dimethylaminoethyl- 57.5/7.5/31.5/3.5
    [1,3]-dioxolane(XTC) lipid:siRNA~6:1
    LNP06 2,2-Dilinoleyl-4- XTC/DSPC/Cholesterol/PEG-DMG Extrusion
    dimethylaminoethyl- 57.5/7.5/31.5/3.5
    [1,3]-dioxolane(XTC) lipid:siRNA~11:1
    LNP07 2,2-Dilinoleyl-4- XTC/DSPC/Cholesterol/PEG-DMG In-line
    dimethylaminoethyl- 60/7.5/31/1.5, mixing
    [1,3]-dioxolane(XTC) lipid:siRNA~6:1
    LNP08 2,2-Dilinoleyl-4- XTC/DSPC/Cholesterol/PEG-DMG In-line
    dimethylaminoethyl- 60/7.5/31/1.5, mixing
    [1,3]-dioxolane(XTC) lipid:siRNA~11:1
    LNP09 2,2-Dilinoleyl-4- XTC/DSPC/Cholesterol/PEG-DMG In-line
    dimethylaminoethyl- 50/10/38.5/1.5 mixing
    [1,3]-dioxolane(XTC) Lipid:siRNA 10:1
    SNALP 1,2-Dilinolenyloxy- DLinDMA/DPPC/Cholesterol/PEG-cDMA
    N,N- (57.1/7.1/34.4/1.4)
    dimethylaminopropane lipid:siRNA~7:1
    (DLinDMA)
    SNALP- 2,2-Dilinoleyl-4- XTC/DPPC/Cholesterol/PEG-cDMA
    XTC dimethylaminoethyl- 57.1/7.1/34.4/1.4
    [1,3]-dioxolane(XTC) lipid:siRNA~7:1
  • Characterization of Lipid Formulated dsRNAs
  • Formulations prepared by either the in-line mixing or extrusion-free method can be characterized in similar manners. For example, formulations are typically characterized by visual inspection. They should be whitish translucent solutions free from aggregates or sediment. Particle size and particle size distribution of lipid-nanoparticles can be measured by light scattering using, for example, a Malvern Zetasizer Nano ZS (Malvern, USA). Particles should be about 20-300 nm, such as 40-100 nm in size. The particle size distribution should be unimodal. The total siRNA concentration in the formulation, as well as the entrapped fraction, is estimated using a dye exclusion assay. A sample of the formulated siRNA can be incubated with an RNA-binding dye, such as Ribogreen (Molecular Probes) in the presence or absence of a formulation disrupting surfactant, e.g., 0.5% Triton-X100. The total siRNA in the formulation can be determined by the signal from the sample containing the surfactant, relative to a standard curve. The entrapped fraction is determined by subtracting the “free” siRNA content (as measured by the signal in the absence of surfactant) from the total siRNA content. Percent entrapped siRNA is typically >85%. For SNALP formulation, the particle size is at least 30 nm, at least 40 nm, at least 50 nm, at least 60 nm, at least 70 nm, at least 80 nm, at least 90 nm, at least 100 nm, at least 110 nm, and at least 120 nm. The suitable range is typically about at least 50 nm to about at least 110 nm, about at least 60 nm to about at least 100 nm, or about at least 80 nm to about at least 90 nm.
  • Penetration Enhancers
  • In one embodiment, the present invention employs various penetration enhancers to effect the efficient delivery of nucleic acids, particularly dsRNAs, to the skin of animals. Most drugs are present in solution in both ionized and nonionized forms. However, usually only lipid soluble or lipophilic drugs readily cross cell membranes. It has been discovered that even non-lipophilic drugs may cross cell membranes if the membrane to be crossed is treated with a penetration enhancer. In addition to aiding the diffusion of non-lipophilic drugs across cell membranes, penetration enhancers also enhance the permeability of lipophilic drugs.
  • Penetration enhancers may be classified as belonging to one of five broad categories, i.e., surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92). Each of the above mentioned classes of penetration enhancers are described below in greater detail.
  • Surfactants: In connection with the present invention, surfactants (or “surface-active agents”) are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between the aqueous solution and another liquid, with the result that absorption of dsRNAs through the mucosa is enhanced. In addition to bile salts and fatty acids, these penetration enhancers include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p. 92); and perfluorochemical emulsions, such as FC-43. Takahashi et al., J. Pharm. Pharmacol., 1988, 40, 252).
  • Fatty acids: Various fatty acids and their derivatives which act as penetration enhancers include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (1-monooleoyl-rac-glycerol), dilaurin, caprylic acid, arachidonic acid, glycerol 1-monocaprate, 1-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines, C.sub.1-10 alkyl esters thereof (e.g., methyl, isopropyl and t-butyl), and mono- and di-glycerides thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (Lee et al., Critical Reviews in Therapeutic Drug Carryier Systems, 1991, p. 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; El Hariri et al., J. Pharm. Pharmacol., 1992, 44, 651-654).
  • Bile salts: The physiological role of bile includes the facilitation of dispersion and absorption of lipids and fat-soluble vitamins (Brunton, Chapter 38 in: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al. Eds., McGraw-Hill, New York, 1996, pp. 934-935). Various natural bile salts, and their synthetic derivatives, act as penetration enhancers. Thus the term “bile salts” includes any of the naturally occurring components of bile as well as any of their synthetic derivatives. The bile salts of the invention include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholic acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate and polyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Swinyard, Chapter 39 In: Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, Pa., 1990, pages 782-783; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Yamamoto et al., J. Pharm. Exp. Ther., 1992, 263, 25; Yamashita et al., J. Pharm. Sci., 1990, 79, 579-583).
  • Chelating Agents: Chelating agents, as used in connection with the present invention, can be defined as compounds that remove metallic ions from solution by forming complexes therewith, with the result that absorption of dsRNAs through the mucosa is enhanced. With regards to their use as penetration enhancers in the present invention, chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett, J. Chromatogr., 1993, 618, 315-339). Chelating agents of the invention include but are not limited to disodium ethylenediaminetetraacetate (EDTA), citric acid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of beta-diketones (enamines) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Buur et al., J. Control Rel., 1990, 14, 43-51).
  • Non-chelating non-surfactants: As used herein, non-chelating non-surfactant penetration enhancing compounds can be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absorption of dsRNAs through the alimentary mucosa (Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33). This class of penetration enhancers include, for example, unsaturated cyclic ureas, 1-alkyl- and 1-alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and non-steroidal anti-inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al., J. Pharm. Pharmacol., 1987, 39, 621-626).
  • Agents that enhance uptake of dsRNAs at the cellular level may also be added to the pharmaceutical and other compositions of the present invention. For example, cationic lipids, such as lipofectin (Junichi et al, U.S. Pat. No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), are also known to enhance the cellular uptake of dsRNAs.
  • Other agents may be utilized to enhance the penetration of the administered nucleic acids, including glycols such as ethylene glycol and propylene glycol, pyrrols such as 2-pyrrol, azones, and terpenes such as limonene and menthone.
  • Carriers
  • Certain compositions of the present invention also incorporate carrier compounds in the formulation. As used herein, “carrier compound” or “carrier” can refer to a nucleic acid, or analog thereof, which is inert (i.e., does not possess biological activity per se) but is recognized as a nucleic acid by in vivo processes that reduce the bioavailability of a nucleic acid having biological activity by, for example, degrading the biologically active nucleic acid or promoting its removal from circulation. The coadministration of a nucleic acid and a carrier compound, typically with an excess of the latter substance, can result in a substantial reduction of the amount of nucleic acid recovered in the liver, kidney or other extracirculatory reservoirs, presumably due to competition between the carrier compound and the nucleic acid for a common receptor. For example, the recovery of a partially phosphorothioate dsRNA in hepatic tissue can be reduced when it is coadministered with polyinosinic acid, dextran sulfate, polycytidic acid or 4-acetamido-4′ isothiocyano-stilbene-2,2′-disulfonic acid (Miyao et al., DsRNA Res. Dev., 1995, 5, 115-121; Takakura et al., DsRNA & Nucl. Acid Drug Dev., 1996, 6, 177-183.
  • Excipients
  • In contrast to a carrier compound, a “pharmaceutical carrier” or “excipient” is a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal. The excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a nucleic acid and the other components of a given pharmaceutical composition. Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); and wetting agents (e.g., sodium lauryl sulphate, etc).
  • Pharmaceutically acceptable organic or inorganic excipient suitable for non-parenteral administration which do not deleteriously react with nucleic acids can also be used to formulate the compositions of the present invention. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.
  • Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions of the nucleic acids in liquid or solid oil bases. The solutions may also contain buffers, diluents and other suitable additives. Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can be used.
  • Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.
  • Other Components
  • The compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention. The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation.
  • Aqueous suspensions may contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.
  • Certain embodiments of the invention provide pharmaceutical compositions containing (a) one or more antisense compounds and (b) one or more other chemotherapeutic agents which function by a non-antisense mechanism. Examples of such chemotherapeutic agents include but are not limited to daunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, hydroxyurea, deoxycoformycin, 4-hydroxyperoxycyclophosphor-amide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol, vincristine, vinblastine, etoposide (VP-16), trimetrexate, irinotecan, topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When used with the compounds of the invention, such chemotherapeutic agents may be used individually (e.g., 5-FU and oligonucleotide), sequentially (e.g., 5-FU and oligonucleotide for a period of time followed by MTX and oligonucleotide), or in combination with one or more other such chemotherapeutic agents (e.g., 5-FU, MTX and oligonucleotide, or 5-FU, radiotherapy and oligonucleotide). Anti-inflammatory drugs, including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, may also be combined in compositions of the invention. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively). Other non-antisense chemotherapeutic agents are also within the scope of this invention. Two or more combined compounds may be used together or sequentially.
  • Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. Compounds which exhibit high therapeutic indices are preferred.
  • The data obtained from cell culture assays and animal studies can be used in formulation a range of dosage for use in humans. The dosage of compositions of the invention lies generally within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range of the compound or, when appropriate, of the polypeptide product of a target sequence (e.g., achieving a decreased concentration of the polypeptide) that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.
  • In addition to their administration, as discussed above, the dsRNAs featured in the invention can be administered in combination with other known agents effective in treatment of pathological processes mediated by GSK-3 expression. In any event, the administering physician can adjust the amount and timing of dsRNA administration on the basis of results observed using standard measures of efficacy known in the art or described herein.
  • Methods for Treating Diseases Caused by Expression of a GSK-3 Gene
  • The invention relates in particular to the use of a dsRNA targeting GSK-3 and compositions containing at least one such dsRNA, for the treatment of a GSK-3-mediated disorder or disease. For example, a dsRNA targeting a GSK-3 gene can be useful for the treatment of manic depression.
  • Other disorders which can be treated with the compounds, compositions and methods described herein include a metabolic disease, such as metabolic disorders (e.g., Type I or Type II diabetes or metabolic syndrome) and nervous system disorders, (e.g., CNS or nuerogenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, Huntington's Disease, prion diseases (e.g., transmissible spongiform encephalopathies), stroke and schizophrenia). Compositions and methods for treating pathological conditions and diseases such as protozoan diseases (e.g., Plasmodium falciparum), cancer (e.g., colorectal cancer), and circadian rhythm diseases (e.g., sleep disorders, jet lag, and shift work), and are also provided. The dsRNAs described here can also be used to regulate skeletal muscle growth, inflammatory responses, platelet function, apoptosis, and cellular responses to DNA damage.
  • “Metabolic syndrome” is characterized by a group of metabolic risk factors including: abdominal obesity (excessive fat tissue in and around the abdomen), atherogenic dyslipidemia (blood fat disorders (including high triglycerides, low HDL cholesterol and high LDL cholesterol) that foster plaque build-up in artery walls), elevated blood pressure, insulin resistance or glucose intolerance (due to the body's inability to properly use insulin or blood sugar), a prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor-1 in the blood), and a proinflammatory state (e.g., elevated C-reactive protein in the blood). People with metabolic syndrome are at increased risk of coronary heart disease and other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease), and Type II diabetes. Other metabolic diseases suitable for treatment with a dsRNA targeting GSK-3 include obesity and insulin resistance.
  • A dsRNA targeting GSK-3 can be also be useful for the treatment of cancer, such as a colorectal cancer.
  • A composition containing a dsRNA targeting GSK-3 may also be used to treat other tumors and cancers, such as breast cancer, lung cancer, head and neck cancer, brain cancer, abdominal cancer, colon cancer, colorectal cancer, esophagus cancer, gastrointestinal cancer, glioma, tongue cancer, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, retinoblastoma, Wilm's tumor, multiple myeloma and for the treatment of skin cancer, like melanoma, for the treatment of lymphomas and blood cancer.
  • Owing to the inhibitory effects on GSK-3 expression, a composition according to the invention or a pharmaceutical composition prepared therefrom can enhance the quality of life.
  • The invention further relates to the use of a dsRNA or a pharmaceutical composition thereof, e.g., for treating manic depression or another disorder described herein, in combination with other pharmaceuticals and/or other therapeutic methods, e.g., with known pharmaceuticals and/or known therapeutic methods, such as, for example, those which are currently employed for treating these disorders.
  • For example, in the treatment of manic depression, the patient can also be treated with one or more other therapeutic modalities, e.g., lithium salts, anticonvulsant mood stabilizers, antipsychotics, and other adjunctive treatments described herein. In an embodiment the patient is also treated with lithium salts. Lithium salts have been used as a first-line treatment for bipolar disorder. Common lithium salts are lithium carbonate and (probably less commonly) lithium citrate. Lithium orotate is used as an alternative treatment to lithium carbonate by some individuals with bipolar disorder. In an embodiment the patient is also treated with an anticonvulsant mood stabilizer. Anticonvulsant medications, particularly valproate and carbamazepine, have been used as alternatives or adjuncts to lithium in many cases. Valproate (Depakote, Epival) was FDA approved for the treatment of acute mania in 1995, and is now considered by some doctors to be the first line of therapy for bipolar disorder. A similar medication, valproic acid (Depakene) is also used. Anticonvulsants are also used in combination with antipsychotics. Newer anticonvulsant medications, including lamotrigine and oxcarbazepine, are also effective as mood stabilizers in bipolar disorder. Lamotrigine is particularly promising, as it alleviates bipolar depression and prevents recurrence at higher rates. Zonisamide (trade name Zonegran), another anticonvulsant, also may show promise in treating bipolar depression. Topiramate maybe useful for some patients. It appears to be useful in some treatment resistant cases and for anxiety issues when clonazepam cannot be prescribed. Other anticonvulsants effective in some cases and under study include phenyloin, levetiracetam, pregabalin and valnoctamide. In an embodiment the patient is also treated with an “atypical antipsychotic drug.” The newer atypical antipsychotic drugs such as risperidone, quetiapine, and olanzapine are often used in acutely manic patients. In light of recent evidence, olanzapine (Zyprexa) has been FDA approved as an effective monotherapy for the maintenance of bipolar disorder. Eli Lilly and Company also offers Symbyax, a combination of olanzapine and fluoxetine. Ziprasidone (Geodon) and aripriprazole (Abilify) also show promise. Other newer treatments include Modafinil (Provigil) and Pramipexole (Mirapex), which show promise in treating the cognitive deterioration related to bipolar depression. In addition Riluzole, an ALS treatment, has been shown to be effective treatment. The breast cancer medicine tamoxifen has shown quick response to manic phases. In an embodiment the patient is also treated with electroconvulsive therapy. Electroconvulsive therapy (ECT) is sometimes used to treat severe bipolar depression in cases where other treatments have failed and is 60 to 70 percent effective. In an embodiment the patient is also treated with psychotherapy. Other treatments include omega-3 fatty acids, particularly as a supplement to other medication. There are also reports that medical marijuana can help control the mood swings in some forms of bipolar disorder.
  • In an embodiment a dsRNA described herein is administered to a patient who has previously been treated with another therapeutic or counseling modality but which has provided less than optimal results.
  • In the example of a metabolic disorder, e.g., diabetes, the patient can also be provided administration of a dsRNA targeting GSK-3 can be accompanied by a exercise regimen or by dietary restrictions. A dsRNA featured in the invention can also be administered with a drug or combination of drugs for managing Type II diabetes, e.g., a sulfonylurea, a biguanide, an alpha-glucosidase inhibitor, a thiazolidinedione, a meglitinide, a D-phenylalanine derivative, an amylin synthetic derivatives, an incretin mimetic, or an insulin. Exemplary insulins include regular insulins (Humulin®, Novolin®), insulin lispro (Humalog®), insulin aspart (Novolog®), insulin glulisine (Apidra®), prompt insulin zinc (Semilente®, slightly slower acting), inhaled insulin (Exubera®), intermediate-acting insulins, isophane insulin, neutral protamine Hagedorn (NPH), insulin zinc (Lente®), extended insulin zinc insulin (Ultralente®), insulin glargine (Lantus®), and insulin detemir (Levemir®).
  • In the example of cancerthe patient can also be provided with a chemotherapy agent, such as deoxycoformycin, cisplatin, cyclophosphamide, 5-fluorouracil, adriamycin, daunorubicin, tamoxifen aunorubicin, daunomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, esorubicin, bleomycin, mafosfamide, ifosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, busulfan, mitomycin C, actinomycin D, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, procarbazine, hexamethylmelamine, pentamethylmelamine, mitoxantrone, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, hydroxyurea, deoxycoformycin, 4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), methotrexate (MTX), colchicine, taxol, vincristine, vinblastine, etoposide (VP-16), trimetrexate, irinotecan, topotecan, gemcitabine, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed. 1987, pp. 1206-1228, Berkow et al., eds., Rahway, N.J. When used with the dsRNAs featured in the invention, such chemotherapeutic agents may be used individually (e.g., deoxycoformycin and dsRNA), sequentially (e.g., antiviral and dsRNA for a period of time, followed by deoxycoformycin and dsRNA), or in combination with one or more other such agents (e.g., deoxycoformycin, antiviral and dsRNA, or deoxycoformycin, radiotherapy and dsRNA). Two or more combined compounds may be used together or sequentially.
  • Generally, the dsRNAs described here can be used in combination with other GSK-3 inhibitors. Examples of such inhibitors described in Meijer et al., Trends in Pharmacological Sciences, 25: 471 (September 2004), incorporated herein by reference include pyrroloazepines, (e.g., hymenialdisine), flavones (e.g., flavopiridol), benzazepinones (e.g., kenpaullone, alsterpaulione, and azakenpaullone), bis-indole indirubin-3′-oximes (e.g., indirubin-3′-oxime, 6-bromoindirubin-3′-oxime (BIO), and 6-bromoindirubin-3′-acetoxime), pyrrolopyrazines (e.g., aloisine A and aloisine B), thiadiazolidinones (e.g., TDZD8), pyridyloxadiazoles (e.g., Compound 12), pyrazolopyridines (e.g., pyrazolopyridine 18 and pyrazolopyridine 34), pyrazolopyridazines (e.g., pyrazolopyridine 9), aminopyrimidines (e.g., CHIR98014 and CHIR99021 (CT99021)), pyrazoloquinoxalines (Compound 1), oxindoles (indolinones) (e.g., SU9516), thiazoles (e.g., ARA014418), bisindolylmaleimides (e.g., staurosporine and Compound 5a), azaindolylmaleimides (e.g., Compound 29 and Compound 46), bisindolylmaleimides (e.g., GF109203x (bisindolylmaleimide I) and Ro318220 (bisindolylmaleimide IX)), arylindolemaleimides (e.g., SB216763), anilinomaleimides (e.g., SB415286), anilinoarylmaleimides (e.g., IS), phenylaminopyrimidines (e.g., CGP60474), triazoles (e.g., Compound 8b), pyrrolopyrimidines (e.g., TWS119), pyrazolopyrimidines (e.g., Compound 1A), chloromethyl thienyl ketone (e.g., Compound 17), atoms in competition with Mg2+ (e.g., lithium), atoms in competition with Mg2+ and ATP (e.g., beryllium), and uncompetitive atoms (e.g., zinc). Structures for some of the inhibitors can be found in FIG. 2 of Meijer et al. and are shown below.
  • Figure US20110184046A1-20110728-C00002
    Figure US20110184046A1-20110728-C00003
    Figure US20110184046A1-20110728-C00004
    Figure US20110184046A1-20110728-C00005
    Figure US20110184046A1-20110728-C00006
    Figure US20110184046A1-20110728-C00007
  • Methods for Inhibiting Expression of the GSK-3 Gene
  • In yet another aspect, the invention provides a method for inhibiting the expression of an GSK-3 gene in a mammal. The method includes administering a composition featured in the invention to the mammal such that expression of the target GSK-3 gene is silenced.
  • When the organism to be treated is a mammal such as a human, the composition may be administered by any means known in the art including, but not limited to oral or parenteral routes, including intravenous, intramuscular, subcutaneous, transdermal, airway (aerosol), nasal, rectal, and topical (including buccal and sublingual) administration. In preferred embodiments, the compositions are administered by intravenous infusion or injection.
  • Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
  • EXAMPLE Example 1 Design and Synthesis of siRNA Targeting GSK3
  • siRNA Design for Mouse Glycogen Synthase Kinase 3 Alpha (GSK3α)
  • All possible perfect match sense 19 mer oligomers were extracted from mouse GSKalpha sequence NM001031667.1, the sole NCBI reference sequence for the mouse GSK3α gene, and identified as candidate target regions. The sequences are shown in Table 1 below.
  • In order to rank candidate target sequences and their corresponding siRNAs and select appropriate ones, their predicted potential for interacting with irrelevant targets (off-target potential) was taken as the primary ranking parameter. siRNAs with low off-target potential were defined as preferable and assumed to be more specific in vivo.
  • To identify potential off-target genes, 19 mer candidate sequences as well as their 19 mer reverse complements were subjected to a homology search against the entire NCBI mouse reference mRNA sequence collection using the FASTA search algorithm (Pearson, W R, Lipman, D J. Improved Tools for Biological Sequence Comparison. PNAS (1988) 85: 2444-8.).
  • The following off-target properties for every 19 mer were extracted for each oligo-mouse transcript alignment to calculate the off-target score:
      • 1. Number of mismatches in seed region, defined as positions 2-9 of the oligomer
      • 2. Number of mismatches in cleavage site region, defined as positions 10 and 11
  • 3. Number of mismatches in non-seed region, non-cleavage region, defined as positions 12-19
      • 4. Mismatches in position 1 were ignored
  • The off-target score for each oligo-transcript pair was calculated for considering assumptions 1 to 3 as follows:

  • Off-target score=(number of seed mismatches*2.8)+(number of cleavage site mismatches*1.2)+(number of non-seed mismatches*1)
  • The most relevant off-target gene for each siRNA corresponding to the input 19 mer sequence was defined as the gene with the lowest off-target score. The candidate oligomers were ranked first by the lowest off-target score for the antisense sequence, and secondarily by the lowest off-target score by its sense counterpart. The top 11 oligo sense and antisense pairs from the list were synthesized and their capacity for knockdown of the mouse GSK3α transcript measured. The sequences are shown in Table 4.
  • Sense and antisense oligomers complementary to the human GSK3α gene (NM002093) were designed by first aligning the orthologous transcripts, and then identifying the human counterpart region of the mouse candidate target regions. The sequences are shown in Table 6.
  • siRNA Design for Mouse Glycogen Synthase Kinase 3 Beta (GSK3β)
  • All possible perfect match sense 19 mer oligomers were extracted from NM019827.4 the sole NCBI reference sequence for the mouse Gsk3β gene, and identified as candidate target regions. The sequences are shown in Table 2.
  • In order to rank candidate target sequences and their corresponding siRNAs and select appropriate ones, their predicted potential for interacting with irrelevant targets (off-target potential) was taken as the primary ranking parameter. siRNAs with low off-target potential were defined as preferable and assumed to be more specific in vivo.
  • To identify potential off-target genes, 19 mer candidate sequences as well as their 19 mer reverse complements were subjected to a homology search against the entire NCBI mouse reference mRNA sequence collection using the FASTA search algorithm (Pearson, W R, Lipman, D J. Improved Tools for Biological Sequence Comparison. PNAS (1988) 85: 2444-8).
  • The following off-target properties for every 19 mer were extracted for each oligo-mouse transcript alignment to calculate the off-target score:
      • 1. Number of mismatches in seed region, defined as positions 2-9 of the oligomer
      • 2. Number of mismatches in cleavage site region, defined as positions 10 and 11
      • 3. Number of mismatches in non-seed region, non-cleavage region, defined as positions 12-19
      • 4. Mismatches in position 1 were ignored
  • The off-target score for each oligo-transcript pair was calculated for considering assumptions 1 to 3 as follows:

  • Off-target score=(number of seed mismatches*2.8)+(number of cleavage site mismatches*1.2)+(number of non-seed mismatches*1)
  • The most relevant off-target gene for each siRNA corresponding to the input 19 mer sequence was defined as the gene with the lowest off-target score. The candidate oligomers were ranked first by the lowest off-target score for the antisense sequence, and secondarily by the lowest off-target score by its sense counterpart. The top 11 oligo sense and antisense pairs from the list were synthesized and their capacity for knockdown of the mouse Gsk3 β transcript measured. The sequences are shown in Table 5.
  • Sense and antisense oligomers complementary to the human GSK3β gene (NM019884.2) were designed by first aligning the orthologous transcripts, and then identifying the human counterpart region of the mouse candidate target regions. The sequences are shown in Table 7.
  • Table 3 provides a description of the abbreviations used herein.
  • TABLE 3
    Abbreviations of nucleotide monomers used
    in nucleic acid sequence representation.
    Abbreviationa Nucleotide(s)
    A adenosine-5′-phosphate
    C cytidine-5′-phosphate
    G guanosine-5′-phosphate
    T, dT 2′-deoxy-thymidine-5′-phosphate
    U uridine-5′-phosphate
    N any nucleotide (G, A, C, or T)
    a 2′-O-methyladenosine-5′-phosphate
    c 2′-O-methylcytidine-5′-phosphate
    g 2′-O-methylguanosine-5′-phosphate
    u 2′-O-methyluridine-5′-phosphate
    sT, sdT 2′-deoxy-thymidine-5′phosphate-phosphorothioate
    It will be understood that these monomers, when present in an oligonucleotide, are mutually linked by 5′-3′-phosphodiester bonds.
  • Source of Reagents
  • Where the source of a reagent is not specifically given herein, such reagent may be obtained from any supplier of reagents for molecular biology at a quality/purity standard for application in molecular biology.
  • siRNA Synthesis
  • Single-stranded RNAs can be produced by solid phase synthesis on a scale of 1 μmole using an Expedite 8909 synthesizer (Applied Biosystems, Applera Deutschland GmbH, Darmstadt, Germany) and controlled pore glass (CPG, 500 Å, Proligo Biochemie GmbH, Hamburg, Germany) as solid support. RNA and RNA containing 2′-O-methyl nucleotides can be generated by solid phase synthesis employing the corresponding phosphoramidites and 2′-O-methyl phosphoramidites, respectively (Proligo Biochemie GmbH, Hamburg, Germany). These building blocks can be incorporated at selected sites within the sequence of the oligoribonucleotide chain using standard nucleoside phosphoramidite chemistry such as described in Current protocols in nucleic acid chemistry, Beaucage, S. L. et al. (Edrs.), John Wiley & Sons, Inc., New York, N.Y., USA. Phosphorothioate linkages can be introduced by replacement of the iodine oxidizer solution with a solution of the Beaucage reagent (Chruachem Ltd, Glasgow, UK) in acetonitrile (1%). Further ancillary reagents can be obtained from Mallinckrodt Baker (Griesheim, Germany).
  • Deprotection and purification of the crude oligoribonucleotides by anion exchange HPLC can be carried out according to established procedures. Yields and concentrations can be determined by UV absorption of a solution of the respective RNA at a wavelength of 260 nm using a spectral photometer (DU 640B, Beckman Coulter GmbH, Unterschleiβheim, Germany). Double stranded RNA can be generated by mixing an equimolar solution of complementary strands in annealing buffer (20 mM sodium phosphate, pH 6.8; 100 mM sodium chloride), heated in a water bath at 85-90° C. for 3 minutes and cooled to room temperature over a period of 3-4 hours. The annealed RNA solution can be stored at −20° C. until use.
  • For the synthesis of 3′-cholesterol-conjugated siRNAs (herein referred to as -Chol-3′), an appropriately modified solid support can be used for RNA synthesis. The modified solid support was prepared as follows:
  • Diethyl-2-azabutane-1,4-dicarboxylate AA
  • Figure US20110184046A1-20110728-C00008
  • A 4.7 M aqueous solution of sodium hydroxide (50 mL) can be added into a stirred, ice-cooled solution of ethyl glycinate hydrochloride (32.19 g, 0.23 mole) in water (50 mL). Then, ethyl acrylate (23.1 g, 0.23 mole) can be added and the mixture can be stirred at room temperature until completion of the reaction can be ascertained by TLC. After 19 h the solution can be partitioned with dichloromethane (3×100 mL). The organic layer can be dried with anhydrous sodium sulfate, filtered and evaporated. The residue can be distilled to afford AA (28.8 g, 61%).
  • 3-{Ethoxycarbonylmethyl-[6-(9H-fluoren-9-ylmethoxycarbonyl-amino)-hexanoyl]-amino}-propionic acid ethyl ester AB
  • Figure US20110184046A1-20110728-C00009
  • Fmoc-6-amino-hexanoic acid (9.12 g, 25.83 mmol) can be dissolved in dichloromethane (50 mL) and cooled with ice. Diisopropylcarbodiimde (3.25 g, 3.99 mL, 25.83 mmol) can be added to the solution at 0° C. It can then be followed by the addition of Diethyl-azabutane-1,4-dicarboxylate (5 g, 24.6 mmol) and dimethylamino pyridine (0.305 g, 2.5 mmol). The solution can be brought to room temperature and stirred further for 6 h. Completion of the reaction was ascertained by TLC. The reaction mixture can be concentrated under vacuum and ethyl acetate can be added to precipitate diisopropyl urea. The suspension can be filtered. The filtrate can be washed with 5% aqueous hydrochloric acid, 5% sodium bicarbonate and water. The combined organic layer can be dried over sodium sulfate and concentrated to give the crude product which can be purified by column chromatography (50% EtOAC/Hexanes) to yield 11.87 g (88%) of AB.
  • 3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethyl ester AC
  • Figure US20110184046A1-20110728-C00010
  • 3-{Ethoxycarbonylmethyl-[6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoyl]-amino}-propionic acid ethyl ester AB (11.5 g, 21.3 mmol) can be dissolved in 20% piperidine in dimethylformamide at 0° C. The solution can be stirred continuously for 1 h. The reaction mixture can be concentrated under vacuum, water can be added to the residue, and the product can be extracted with ethyl acetate. The crude product can be purified by conversion into its hydrochloride salt.
  • 3-({6-[17-(1,5-D imethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}ethoxycarbonylmethyl-amino)-propionic acid ethyl ester AD
  • Figure US20110184046A1-20110728-C00011
  • The hydrochloride salt of 3-[(6-Amino-hexanoyl)-ethoxycarbonylmethyl-amino]-propionic acid ethyl ester AC (4.7 g, 14.8 mmol) can be taken up in dichloromethane. The suspension was cooled to 0° C. on ice. To the suspension diisopropylethylamine (3.87 g, 5.2 mL, 30 mmol) can be added. To the resulting solution cholesteryl chloroformate (6.675 g, 14.8 mmol) can be added. The reaction mixture can be stirred overnight. The reaction mixture can be diluted with dichloromethane and washed with 10% hydrochloric acid. The product can be purified by flash chromatography (10.3 g, 92%).
  • 1-{6-[17-(1,5-Dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a] phenanthren-3-yloxycarbonylamino]-hexanoyl}-4-oxo-pyrrolidine-3-carboxylic acid ethyl ester AE
  • Figure US20110184046A1-20110728-C00012
  • Potassium t-butoxide (1.1 g, 9.8 mmol) can be slurried in 30 mL of dry toluene. The mixture can be cooled to 0° C. on ice and 5 g (6.6 mmol) of diester AD can be added slowly with stirring within 20 mins. The temperature can be kept below 5° C. during the addition. The stirring can be continued for 30 mins at 0° C. and 1 mL of glacial acetic acid can be added, immediately followed by 4 g of NaH2PO4.H2O in 40 mL of water. The resultant mixture can be extracted twice with 100 mL of dichloromethane each and the combined organic extracts can be washed twice with 10 mL of phosphate buffer each, dried, and evaporated to dryness. The residue can be dissolved in 60 mL of toluene, cooled to 0° C. and extracted with three 50 mL portions of cold pH 9.5 carbonate buffer. The aqueous extracts can be adjusted to pH 3 with phosphoric acid, and extracted with five 40 mL portions of chloroform which can be combined, dried and evaporated to dryness. The residue can be purified by column chromatography using 25% ethylacetate/hexane to afford 1.9 g of b-ketoester (39%).
  • [6-(3-Hydroxy-4-hydroxymethyl-pyrrolidin-1-yl)-6-oxo-hexyl]-carbamic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester AF
  • Figure US20110184046A1-20110728-C00013
  • Methanol (2 mL) can be added dropwise over a period of 1 h to a refluxing mixture of b-ketoester AE (1.5 g, 2.2 mmol) and sodium borohydride (0.226 g, 6 mmol) in tetrahydrofuran (10 mL). Stirring can be continued at reflux temperature for 1 h. After cooling to room temperature, 1 N HCl (12.5 mL) can be added, the mixture was extracted with ethylacetate (3×40 mL). The combined ethylacetate layer can be dried over anhydrous sodium sulfate and concentrated under vacuum to yield the product which can be purified by column chromatography (10% MeOH/CHCl3) (89%).
  • (6-{3-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-pyrrolidin-1-yl}-6-oxo-hexyl)-carbamic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester AG
  • Figure US20110184046A1-20110728-C00014
  • Diol AF (1.25 gm 1.994 mmol) can be dried by evaporating with pyridine (2×5 mL) in vacuo. Anhydrous pyridine (10 mL) and 4,4′-dimethoxytritylchloride (0.724 g, 2.13 mmol) can be added with stirring. The reaction can be carried out at room temperature overnight. The reaction can be quenched by the addition of methanol. The reaction mixture can be concentrated under vacuum and to the residue dichloromethane (50 mL) was added. The organic layer can be washed with 1M aqueous sodium bicarbonate. The organic layer can be dried over anhydrous sodium sulfate, filtered and concentrated. The residual pyridine can be removed by evaporating with toluene. The crude product can be purified by column chromatography (2% MeOH/Chloroform, Rf=0.5 in 5% MeOH/CHCl3) (1.75 g, 95%).
  • Succinic acid mono-(4-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-1-{6-[17-(1,5-dimethyl-hexyl)-10,13-dimethyl 2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H cyclopenta[a]phenanthren-3-yloxycarbonylamino]-hexanoyl}-pyrrolidin-3-yl) ester AH
  • Figure US20110184046A1-20110728-C00015
  • Compound AG (1.0 g, 1.05 mmol) can be mixed with succinic anhydride (0.150 g, 1.5 mmol) and DMAP (0.073 g, 0.6 mmol) and dried in a vacuum at 40° C. overnight. The mixture can be dissolved in anhydrous dichloroethane (3 mL), triethylamine (0.318 g, 0.440 mL, 3.15 mmol) can be added and the solution can be stirred at room temperature under argon atmosphere for 16 h. It can then be diluted with dichloromethane (40 mL) and washed with ice cold aqueous citric acid (5 wt %, 30 mL) and water (2×20 mL). The organic phase can be dried over anhydrous sodium sulfate and concentrated to dryness. The residue can be used as such for the next step.
  • Cholesterol Derivatised CPG AI
  • Figure US20110184046A1-20110728-C00016
  • Succinate AH (0.254 g, 0.242 mmol) can be dissolved in a mixture of dichloromethane/acetonitrile (3:2, 3 mL). To that solution DMAP (0.0296 g, 0.242 mmol) in acetonitrile (1.25 mL), 2,2′-Dithio-bis(5-nitropyridine) (0.075 g, 0.242 mmol) in acetonitrile/dichloroethane (3:1, 1.25 mL) can be added successively. To the resulting solution triphenylphosphine (0.064 g, 0.242 mmol) in acetonitrile (0.6 ml) was added. The reaction mixture can turn bright orange in color. The solution can be agitated briefly using a wrist-action shaker (5 mins). Long chain alkyl amine-CPG (LCAA-CPG) (1.5 g, 61 mM) can be added. The suspension can be agitated for 2 h. The CPG was filtered through a sintered funnel and washed with acetonitrile, dichloromethane and ether successively. Unreacted amino groups can be masked using acetic anhydride/pyridine. The achieved loading of the CPG can be measured by taking UV measurement (37 mM/g).
  • The synthesis of siRNAs bearing a 5′-12-dodecanoic acid bisdecylamide group (herein referred to as “5′-C32-”) or a 5′-cholesteryl derivative group (herein referred to as “5′-Chol-”) can be performed as described in WO 2004/065601, except that, for the cholesteryl derivative, the oxidation step can be performed using the Beaucage reagent in order to introduce a phosphorothioate linkage at the 5′-end of the nucleic acid oligomer.
  • Example 2 In Vitro Screen of GSK3α and GSK3β siRNAs Against Endogenous GSK3α and GSK3β mRNA Expression in Mouse HT22 Cells
  • Mouse HT22 cells were a gift from Dr. Marcy MacDonald and cultured in Dulbecco's modified Eagle's medium supplied with 10% fetal bovine serum and differentiated in modified serum-free medium (Dulbecco's modified Eagle's medium, N2 supplement, 50 ng/ml nerve growth factor-β, 100 μM phorbol 12,13-dibutyrate, 100 μM dibutyryl cAMP) for 24-48 h before treatment. All treatments were performed in differentiation medium with reduced nerve growth factor-β content (5 ng/ml) at 37° C. in a humidified incubator with 5% CO2.
  • Cells were transfected with the modified siRNA targeting mouse GSK3α or GSK3β described in Table 4 and Table 5. For transfection with siRNA, HT22 cells were seeded at a density of 1.0×105 cells/well in 6-well tissue culture plates and transfected directly. Transfection of siRNA (37.5 nM for single dose screen) was carried out with Lipofectamine-2000 (Invitrogen, Carlsbad, Calif.) as described by the manufacturer. For dose-response curves, siRNA concentrations ranged from 10 nM to 0.1 nM in 10-fold dilutions.
  • 24 hours after transfection, HT22 cells were lysed and cDNA was generated for GSK3α or GSK3β and GAPDH mRNA quantitation. GSK3α or GSK3β mRNA levels were normalized to GAPDH mRNA levels. For each siRNA, 2 individual data points were collected. An siRNA duplex unrelated to the GSK3α or GSK3β gene was used as a control. The activity of a given GSK3α- or GSK313-specific siRNA duplex was expressed as the fraction of the GSK3α or GSK3β mRNA level in treated cells relative to the GSK3α or GSK3β mRNA level in cells treated with the control siRNA duplex.
  • Duplex identifier used in the Figures and in Examples 2-5 refer to the modified version of the duplex, e.g., AD-18821 as used in the Figures and Examples 2-5 refers to the modified version of AD-18821, e.g., AD-18821-b1.
  • FIG. 1 and FIG. 2 provide the results from the in vitro HT22 screen where the siRNAs were tested at a single dose of 37.5 nM. The fraction of GSK3α and GSK3β mRNA remaining in treated cells compared to controls, ±standard deviation, is shown. A number of GSK3α siRNAs (AD-18821, AD-18825 or AD-18832) at 37.5 nM were effective at reducing GSK3α mRNA levels by more than 40%, without affecting GSK3β mRNA levels, in HT22 cells. A number of GSK3β siRNAs (AD-18833, AD-18834, AD-18836, AD-18837, AD-18838, AD-18841, AD-18842, AD-18843 or AD-18844) at 37.5 nM were effective at reducing GSK3 β mRNA levels by more than 40%, without affecting GSK3α mRNA levels, in HT22 cells.
  • FIG. 3 and FIG. 4 show the dose-dependence of selected siRNAs on mRNA reduction in HT22 cells. Several siRNAs targeting GSK3α (AD-18821, AD-18825 or AD-18826) exhibited IC50 values of less than or equal to 1-10 nM in suppressing GSK3α mRNA after transfection into HT22 cells (FIG. 3). Several siRNAs targeting GSK3β (AD-18838 or AD-18843) exhibited IC50 values of less than 1 nM in suppressing GSK3β mRNA (FIG. 4).
  • Example 3 GSK3β dsRNAs reduce endogenous GSK3β protein in HT22 cells
  • HT22 cells were cultured and transfected as previously described with 75 nM of 11 siRNAs against GSK3β (AD-18833, AD-18834, AD-18835, AD-18836, AD-18837, AD-18838, AD-18839, AD-18841, AD-18842, AD-18843 or AD-18844); one control unrelated siRNA (AD-1955) or Lipofectamine-2000 alone (Control). 48 hours post-transfection, the cells were harvested and lysed. Proteins in the lysates were separated on a denaturing polyacrylamide gel. GSK3β and β-actin were detected by standard western blot protocols using antibodies that bind to the proteins. For GSK3β detection, the membrane was probed with a monoclonal GSK3β antibody produced in rabbit (Cell Signaling, Danvers, Mass.) followed by a secondary antibody donkey anti-rabbit IgG horseradish peroxidase (GE Healthcare, Piscataway, N.J.). β-actin was detected by mouse anti-actin antibody (Sigma, St. Louis, Mo.) followed by a Sheep anti-mouse IgG horseradish peroxidase secondary antibody (GE Healthcare, Piscataway, N.J.).
  • FIG. 5 provides the results. AD-18838, AD-18843 and AD-18844, all at 75 nM, decreased the level of GSK3β protein relative to the control protein β-actin, whereas the control unrelated siRNA had no effect on the level of GSK3β protein. These results demonstrate that dsRNAs targeting GSK3β effectively reduce not only GSK3β mRNA levels, but also GSK3β protein levels.
  • Example 4 In Vivo Down-Modulation of Endogenous GSK3α or GSK3β mRNA Levels by CNS Administration of GSK3α or GSK3β dsRNAs in Mice
  • To assess the biological activity of GSK3 dsRNAs in vivo, dsRNAs targeting GSK3α(AD-18821, AD-18825, and AD-18826) or GSK3β (AD-18838, AD-18843, and AD-18844) were evaluated.
  • In mice, 1.26 mg AD-18821, AD-18825, AD-18826, AD-18838, AD-18843, AD-18844, or phosphate-buffered saline (PBS, vehicle control) was administered by continuous infusion into the nucleus accumbens over 14 days. Ten week old male C57BL6 mice (Charles River Laboratory) received stereotaxic implantations of 30-gauge infusion cannulae (Plastics One, Roanok, Va.) such that unilateral infusions were targeted to the nucleus accumbens (anteroposterior +1.1 mm, mediolateral +1.3 mm, relative to bregma; dorsoventral 4.5 mm, relative to skull surface). Mini-osmotic pumps (model 1002) were primed overnight according to the manufacturer's specifications, implanted subcutaneously, and connected via catheters, to deliver (6 mice per treatment group) PBS, 1.1 mM (15 mg/mL) of GSK3α siRNAs (AD-18821, AD-18825, or AD-18826) or 1.1 mM (15 mg/mL) of GSK3β siRNAs (AD-18838, AD-18843, or AD-18844) at 0.25 μL/hr over 14 days. At the end of the 14 day infusion period, animals were sacrificed, brains were removed, and 1.2 mm punches from the ipsilateral nucleus accumbens encompassing the infusion site, from 1 mm thick coronal brain slabs, were flash frozen and stored at −80° C. Individual brain punches from each mouse were quantified for GSK3α and GSK3β mRNA. Each brain punch was run in triplicate for RT-qPCR. Approximately 60 ng of total RNA in a 20 μl total reaction volume was used for RT-qPCR. GSK3α and GSK3β primers were custom designed and obtained from IDT (Integrated DNA Technologies, Inc., Coralville, Iowa). RT-qPCR was run with SBYR. GAPDH was used as the internal control for normalization. Relative expression of GSK3α and GSK3β mRNA was quantified by 2ΔCt (where ΔCt=Ctgene−CtGAPDH).
  • The GSK3β siRNAs, AD-18844, AD-18838 or AD-18843, showed 53% (ANOVA; p=0.012) (FIG. 6), 28% or 25% GSK3β mRNA reduction in the ipsilateral nucleus accumbens, respectively, compared to PBS control. The GSK3β siRNA, AD-18844, had no effect on GSK3αmRNA levels. The GSK3α siRNAs, AD-18826, AD-18825 or AD-18821, showed 51% (p=0.052; Tukey Post-hoc ANOVA) (FIG. 7), 42% (t-test; p=0.004) or 15% GSK3α mRNA reduction in the ipsilateral nucleus accumbens, respectively, compared to PBS control. The GSK3α siRNA, AD-18826, had no effect on GSK3β mRNA levels.
  • These results demonstrate that infusion into the nucleus accumbens of AD-18844 and AD-18826 are efficacious in vivo in specifically down-modulating GSK3β and GSK3α mRNA levels, respectively, in the nucleus accumbens.
  • Example 5 Inhibition of GSK-3 Expression in Human Cells
  • A set of siRNA targeting human GSK3α and GSK3β (Table 6 and Table 7) are evaluated for inhibition of GSK-3 expression in human cell lines. Human cell lines expressing endogenouseGSK3 are transfected with at least one of the duplexes in Table 6 or Table 7, e.g., huGSKA-3 (orthologous to AD-18826-b1) and/or huGSKB-11 (orthologous to AD-18826-b1).
  • The human duplexes can be modified in a similar manner to the mouse duplexes. The transfected cells are assayed for effects on mRNA and protein levels using techniques described herein and known to one of skill in the art.
  • Example 6 Inhibition of GSK-3 Expression in Humans
  • A human subject is treated with a pharmaceutical composition comprising a pharmaceutical formulation of an siRNA targeting a human GSK-3 gene.
  • A subject in need of treatment is selected or identified. The subject can be in need of treatment for manic depression, a metabolic disease, a nervous system disorders, or cancer.
  • At time zero, a suitable first dose of the composition is subcutaneously administered to the subject. The composition is formulated as described herein. After a period of time, the subject's condition is evaluated, e.g., by measurement episodes of mania, episodes of depression, and the like. This measurement can be accompanied by a measurement of GSK-3 expression in said subject, and/or the products of the successful siRNA-targeting of GSK-3. Other relevant criteria can also be measured. The number and strength of doses are adjusted according to the subject's needs.
  • After treatment, the subject's condition is compared to the condition existing prior to the treatment, or relative to the condition of a similarly afflicted but untreated subject.
  • TABLE 1
    Sequences of duplexes targeting Mouse GSK3-alpha
    Sequences of possible duplexes targeting mouse GSK3-alpha.
    Target sequence location identifies target sequence in mouse
    GSK3-alpha mRNA NM_001031667.1. Unmodified sense
    strand is identical to target sequence. Unmodified a antisense
    strand is complementary to target sequence.
    Target SEQ SEQ
    sequence ID Unmodified sequence ID Modified sequence
    location NO: 5′ to 3′ NO: 5′ to 3′ Strand
    670-689 1 AACUGCAGAUUAUGCGUAA 2 AAcuGcAGAuuAuGcGuAAdTsdT sense
    670-689 3 UUACGCAUAAUCUGCAGUU 4 UuACGcAuAAUCUGcAGUUdTsdT antis
    1074-1093 5 ACAGAUUACACCUCGUCCA 6 AcAGAuuAcAccucGuccAdTsdT sense
    1074-1093 7 UGGACGAGGUGUAAUCUGU 8 UGGACGAGGUGuAAUCUGUdTsdT antis
    330-349 9 GGCGGCGGGAAAGCGUCAG 10 GGcGGcGGGAAAGcGucAGdTsdT sense
    330-349 11 CUGACGCUUUCCCGCCGCC 12 CUGACGCUUUCCCGCCGCCdTsdT antis
    239-258 13 GGCGCGGACCAGCUCGUUC 14 GGcGcGGAccAGcucGuucdTsdT sense
    239-258 15 GAACGAGCUGGUCCGCGCC 16 GAACGAGCUGGUCCGCGCCdTsdT antis
    1340-1359 17 CCUACUGGAGUACACGCCA 18 ccuAcuGGAGuAcAcGccAdTsdT sense
    1340-1359 19 UGGCGUGUACUCCAGUAGG 20 UGGCGUGuACUCcAGuAGGdTsdT antis
    1342-1361 21 UACUGGAGUACACGCCAUC 22 uAcuGGAGuAcAcGccAucdTsdT sense
    1342-1361 23 GAUGGCGUGUACUCCAGUA 24 GAUGGCGUGuACUCcAGuAdTsdT antis
    1073-1092 25 CACAGAUUACACCUCGUCC 26 cAcAGAuuAcAccucGuccdTsdT sense
    1073-1092 27 GGACGAGGUGUAAUCUGUG 28 GGACGAGGUGuAAUCUGUGdTsdT antis
    1236-1255 29 CCUAACUAUACGGAGUUCA 30 ccuAAcuAuAcGGAGuucAdTsdT sense
    1236-1255 31 UGAACUCCGUAUAGUUAGG 32 UGAACUCCGuAuAGUuAGGdTsdT antis
    435-454 33 GCGGGCACUAGCUUCCCGC 34 GcGGGcAcuAGcuucccGcdTsdT sense
    435-454 35 GCGGGAAGCUAGUGCCCGC 36 GCGGGAAGCuAGUGCCCGCdTsdT antis
    1231-1250 37 UGAACCCUAACUAUACGGA 38 uGAAcccuAAcuAuAcGGAdTsdT sense
    1231-1250 39 UCCGUAUAGUUAGGGUUCA 40 UCCGuAuAGUuAGGGUUcAdTsdT antis
    1234-1253 41 ACCCUAACUAUACGGAGUU 42 AcccuAAcuAuAcGGAGuudTsdT sense
    1234-1253 43 AACUCCGUAUAGUUAGGGU 44 AACUCCGuAuAGUuAGGGUdTsdT antis
    1235-1254 45 CCCUAACUAUACGGAGUUC 46 cccuAAcuAuAcGGAGuucdTsdT sense
    1235-1254 47 GAACUCCGUAUAGUUAGGG 48 GAACUCCGuAuAGUuAGGGdTsdT antis
    1233-1252 49 AACCCUAACUAUACGGAGU 50 AAcccuAAcuAuAcGGAGudTsdT sense
    1233-1252 51 ACUCCGUAUAGUUAGGGUU 52 ACUCCGuAuAGUuAGGGUUdTsdT antis
    2027-2046 53 GCCCCCUGGGUGUAAAUAG 54 GcccccuGGGuGuAAAuAGdTsdT sense
    2027-2046 55 CUAUUUACACCCAGGGGGC 56 CuAUUuAcACCcAGGGGGCdTsdT antis
     5-24 57 UGACAACGAAGCCGACGGC 58 uGAcAAcGAAGccGAcGGcdTsdT sense
     5-24 59 GCCGUCGGCUUCGUUGUCA 60 GCCGUCGGCUUCGUUGUcAdTsdT antis
    1071-1090 61 GCCACAGAUUACACCUCGU 62 GccAcAGAuuAcAccucGudTsdT sense
    1071-1090 63 ACGAGGUGUAAUCUGUGGC 64 ACGAGGUGuAAUCUGUGGCdTsdT antis
    2000-2019 65 AGCCCAUCUCUCGUCUUCC 66 AGcccAucucucGucuuccdTsdT sense
    2000-2019 67 GGAAGACGAGAGAUGGGCU 68 GGAAGACGAGAGAUGGGCUdTsdT antis
     4-23 69 GUGACAACGAAGCCGACGG 70 GuGAcAAcGAAGccGAcGGdTsdT sense
     4-23 71 CCGUCGGCUUCGUUGUCAC 72 CCGUCGGCUUCGUUGUcACdTsdT antis
    1085-1104 73 CUCGUCCAUCGAUGUGUGG 74 cucGuccAucGAuGuGuGGdTsdT sense
    1085-1104 75 CCACACAUCGAUGGACGAG 76 CcAcAcAUCGAUGGACGAGdTsdT antis
    2070-2089 77 AAACGUCAAUUCACACCAU 78 AAAcGucAAuucAcAccAudTsdT sense
    2070-2089 79 AUGGUGUGAAUUGACGUUU 80 AUGGUGUGAAUUGACGUUUdTsdT antis
    2072-2091 81 ACGUCAAUUCACACCAUUC 82 AcGucAAuucAcAccAuucdTsdT sense
    2072-2091 83 GAAUGGUGUGAAUUGACGU 84 GAAUGGUGUGAAUUGACGUdTsdT antis
    251-270 85 CUCGUUCGCGGAGCCAGGA 86 cucGuucGcGGAGccAGGAdTsdT sense
    251-270 87 UCCUGGCUCCGCGAACGAG 88 UCCUGGCUCCGCGAACGAGdTsdT antis
    241-260 89 CGCGGACCAGCUCGUUCGC 90 cGcGGAccAGcucGuucGcdTsdT sense
    241-260 91 GCGAACGAGCUGGUCCGCG 92 GCGAACGAGCUGGUCCGCGdTsdT antis
    581-600 93 CGGAGUAGUAUACCAGGCA 94 cGGAGuAGuAuAccAGGcAdTsdT sense
    581-600 95 UGCCUGGUAUACUACUCCG 96 UGCCUGGuAuACuACUCCGdTsdT antis
    1076-1095 97 AGAUUACACCUCGUCCAUC 98 AGAuuAcAccucGuccAucdTsdT sense
    1076-1095 99 GAUGGACGAGGUGUAAUCU 100 GAUGGACGAGGUGuAAUCUdTsdT antis
    2069-2088 101 AAAACGUCAAUUCACACCA 102 AAAAcGucAAuucAcAccAdTsdT sense
    2069-2088 103 UGGUGUGAAUUGACGUUUU 104 UGGUGUGAAUUGACGUUUUdTsdT antis
     6-25 105 GACAACGAAGCCGACGGCA 106 GAcAAcGAAGccGAcGGcAdTsdT sense
     6-25 107 UGCCGUCGGCUUCGUUGUC 108 UGCCGUCGGCUUCGUUGUCdTsdT antis
    16-35 109 CCGACGGCAGAGGGACUUC 110 ccGAcGGcAGAGGGAcuucdTsdT sense
    16-35 111 GAAGUCCCUCUGCCGUCGG 112 GAAGUCCCUCUGCCGUCGGdTsdT antis
    243-262 113 CGGACCAGCUCGUUCGCGG 114 cGGAccAGcucGuucGcGGdTsdT sense
    243-262 115 CCGCGAACGAGCUGGUCCG 116 CCGCGAACGAGCUGGUCCGdTsdT antis
    244-263 117 GGACCAGCUCGUUCGCGGA 118 GGAccAGcucGuucGcGGAdTsdT sense
    244-263 119 UCCGCGAACGAGCUGGUCC 120 UCCGCGAACGAGCUGGUCCdTsdT antis
    328-347 121 CUGGCGGCGGGAAAGCGUC 122 cuGGcGGcGGGAAAGcGucdTsdT sense
    328-347 123 GACGCUUUCCCGCCGCCAG 124 GACGCUUUCCCGCCGCcAGdTsdT antis
    331-350 125 GCGGCGGGAAAGCGUCAGU 126 GcGGcGGGAAAGcGucAGudTsdT sense
    331-350 127 ACUGACGCUUUCCCGCCGC 128 ACUGACGCUUUCCCGCCGCdTsdT antis
    340-359 129 AAGCGUCAGUCGGGGCUAU 130 AAGcGucAGucGGGGcuAudTsdT sense
    340-359 131 AUAGCCCCGACUGACGCUU 132 AuAGCCCCGACUGACGCUUdTsdT antis
    432-451 133 GGCGCGGGCACUAGCUUCC 134 GGcGcGGGcAcuAGcuuccdTsdT sense
    432-451 135 GGAAGCUAGUGCCCGCGCC 136 GGAAGCuAGUGCCCGCGCCdTsdT antis
    655-674 137 GGUUCAAGAACCGAGAACU 138 GGuucAAGAAccGAGAAcudTsdT sense
    655-674 139 AGUUCUCGGUUCUUGAACC 140 AGUUCUCGGUUCUUGAACCdTsdT antis
    1024-1043 141 CCUACAUCUGCUCUCGGUA 142 ccuAcAucuGcucucGGuAdTsdT sense
    1024-1043 143 UACCGAGAGCAGAUGUAGG 144 uACCGAGAGcAGAUGuAGGdTsdT antis
    1075-1094 145 CAGAUUACACCUCGUCCAU 146 cAGAuuAcAccucGuccAudTsdT sense
    1075-1094 147 AUGGACGAGGUGUAAUCUG 148 AUGGACGAGGUGuAAUCUGdTsdT antis
    1089-1108 149 UCCAUCGAUGUGUGGUCGG 150 uccAucGAuGuGuGGucGGdTsdT sense
    1089-1108 151 CCGACCACACAUCGAUGGA 152 CCGACcAcAcAUCGAUGGAdTsdT antis
    1090-1109 153 CCAUCGAUGUGUGGUCGGC 154 ccAucGAuGuGuGGucGGcdTsdT sense
    1090-1109 155 GCCGACCACACAUCGAUGG 156 GCCGACcAcAcAUCGAUGGdTsdT antis
    1092-1111 157 AUCGAUGUGUGGUCGGCUG 158 AucGAuGuGuGGucGGcuGdTsdT sense
    1092-1111 159 CAGCCGACCACACAUCGAU 160 cAGCCGACcAcAcAUCGAUdTsdT antis
    1093-1112 161 UCGAUGUGUGGUCGGCUGG 162 ucGAuGuGuGGucGGcuGGdTsdT sense
    1093-1112 163 CCAGCCGACCACACAUCGA 164 CcAGCCGACcAcAcAUCGAdTsdT antis
    1230-1249 165 AUGAACCCUAACUAUACGG 166 AuGAAcccuAAcuAuAcGGdTsdT sense
    1230-1249 167 CCGUAUAGUUAGGGUUCAU 168 CCGuAuAGUuAGGGUUcAUdTsdT antis
    1348-1367 169 AGUACACGCCAUCCUCAAG 170 AGuAcAcGccAuccucAAGdTsdT sense
    1348-1367 171 CUUGAGGAUGGCGUGUACU 172 CUUGAGGAUGGCGUGuACUdTsdT antis
    1401-1420 173 UUCGAUGAACUGCGGAGAC 174 uucGAuGAAcuGcGGAGAcdTsdT sense
    1401-1420 175 GUCUCCGCAGUUCAUCGAA 176 GUCUCCGcAGUUcAUCGAAdTsdT antis
    1402-1421 177 UCGAUGAACUGCGGAGACU 178 ucGAuGAAcuGcGGAGAcudTsdT sense
    1402-1421 179 AGUCUCCGCAGUUCAUCGA 180 AGUCUCCGcAGUUcAUCGAdTsdT antis
    1489-1508 181 UCCAACCAUCUCUCAAUGC 182 uccAAccAucucucAAuGcdTsdT sense
    1489-1508 183 GCAUUGAGAGAUGGUUGGA 184 GcAUUGAGAGAUGGUUGGAdTsdT antis
    1999-2018 185 CAGCCCAUCUCUCGUCUUC 186 cAGcccAucucucGucuucdTsdT sense
    1999-2018 187 GAAGACGAGAGAUGGGCUG 188 GAAGACGAGAGAUGGGCUGdTsdT antis
    2028-2047 189 CCCCCUGGGUGUAAAUAGA 190 cccccuGGGuGuAAAuAGAdTsdT sense
    2028-2047 191 UCUAUUUACACCCAGGGGG 192 UCuAUUuAcACCcAGGGGGdTsdT antis
    2068-2087 193 GAAAACGUCAAUUCACACC 194 GAAAAcGucAAuucAcAccdTsdT sense
    2068-2087 195 GGUGUGAAUUGACGUUUUC 196 GGUGUGAAUUGACGUUUUCdTsdT antis
    2080-2099 197 UCACACCAUUCAACUUGCC 198 ucAcAccAuucAAcuuGccdTsdT sense
    2080-2099 199 GGCAAGUUGAAUGGUGUGA 200 GGcAAGUUGAAUGGUGUGAdTsdT antis
    2083-2102 201 CACCAUUCAACUUGCCCCC 202 cAccAuucAAcuuGcccccdTsdT sense
    2083-2102 203 GGGGGCAAGUUGAAUGGUG 204 GGGGGcAAGUUGAAUGGUGdTsdT antis
    2084-2103 205 ACCAUUCAACUUGCCCCCC 206 AccAuucAAcuuGccccccdTsdT sense
    2084-2103 207 GGGGGGCAAGUUGAAUGGU 208 GGGGGGcAAGUUGAAUGGUdTsdT antis
    2086-2105 209 CAUUCAACUUGCCCCCCCC 210 cAuucAAcuuGccccccccdTsdT sense
    2086-2105 211 GGGGGGGGCAAGUUGAAUG 212 GGGGGGGGcAAGUUGAAUGdTsdT antis
    2244-2263 213 UUGGCAUGAAACCCUUAAA 214 uuGGcAuGAAAcccuuAAAdTsdT sense
    2244-2263 215 UUUAAGGGUUUCAUGCCAA 216 UUuAAGGGUUUcAUGCcAAdTsdT antis
    71-90 217 AGCCGGAGCCCGAACGGCG 218 AGccGGAGcccGAAcGGcGdTsdT sense
    71-90 219 CGCCGUUCGGGCUCCGGCU 220 CGCCGUUCGGGCUCCGGCUdTsdT antis
    177-196 221 CCUGCGCUCGGCGCCAUGA 222 ccuGcGcucGGcGccAuGAdTsdT sense
    177-196 223 UCAUGGCGCCGAGCGCAGG 224 UcAUGGCGCCGAGCGcAGGdTsdT antis
    836-855 225 CACCCCUAUCAUCUACAUC 226 cAccccuAucAucuAcAucdTsdT sense
    836-855 227 GAUGUAGAUGAUAGGGGUG 228 GAUGuAGAUGAuAGGGGUGdTsdT antis
    929-948 229 GCCCCAGAAUUUGCUUGUG 230 GccccAGAAuuuGcuuGuGdTsdT sense
    929-948 231 CACAAGCAAAUUCUGGGGC 232 cAcAAGcAAAUUCUGGGGCdTsdT antis
    1001-1020 233 GGUUCGGGGGGAGCCCAAU 234 GGuucGGGGGGAGcccAAudTsdT sense
    1001-1020 235 AUUGGGCUCCCCCCGAACC 236 AUUGGGCUCCCCCCGAACCdTsdT antis
    1091-1110 237 CAUCGAUGUGUGGUCGGCU 238 cAucGAuGuGuGGucGGcudTsdT sense
    1091-1110 239 AGCCGACCACACAUCGAUG 240 AGCCGACcAcAcAUCGAUGdTsdT antis
    1328-1347 241 ACUCUGCUCUAGCCUACUG 242 AcucuGcucuAGccuAcuGdTsdT sense
    1328-1347 243 CAGUAGGCUAGAGCAGAGU 244 cAGuAGGCuAGAGcAGAGUdTsdT antis
    1338-1357 245 AGCCUACUGGAGUACACGC 246 AGccuAcuGGAGuAcAcGcdTsdT sense
    1338-1357 247 GCGUGUACUCCAGUAGGCU 248 GCGUGuACUCcAGuAGGCUdTsdT antis
    1339-1358 249 GCCUACUGGAGUACACGCC 250 GccuAcuGGAGuAcAcGccdTsdT sense
    1339-1358 251 GGCGUGUACUCCAGUAGGC 252 GGCGUGuACUCcAGuAGGCdTsdT antis
    2059-2078 253 UUUCUUAAAGAAAACGUCA 254 uuucuuAAAGAAAAcGucAdTsdT sense
    2059-2078 255 UGACGUUUUCUUUAAGAAA 256 UGACGUUUUCUUuAAGAAAdTsdT antis
    2067-2086 257 AGAAAACGUCAAUUCACAC 258 AGAAAAcGucAAuucAcAcdTsdT sense
    2067-2086 259 GUGUGAAUUGACGUUUUCU 260 GUGUGAAUUGACGUUUUCUdTsdT antis
    2076-2095 261 CAAUUCACACCAUUCAACU 262 cAAuucAcAccAuucAAcudTsdT sense
    2076-2095 263 AGUUGAAUGGUGUGAAUUG 264 AGUUGAAUGGUGUGAAUUGdTsdT antis
    2089-2108 265 UCAACUUGCCCCCCCCAGC 266 ucAAcuuGccccccccAGcdTsdT sense
    2089-2108 267 GCUGGGGGGGGCAAGUUGA 268 GCUGGGGGGGGcAAGUUGAdTsdT antis
    2231-2250 269 GUUCAAUAAAUUAUUGGCA 270 GuucAAuAAAuuAuuGGcAdTsdT sense
    2231-2250 271 UGCCAAUAAUUUAUUGAAC 272 UGCcAAuAAUUuAUUGAACdTsdT antis
    207-226 273 CCUUCGGGAGGCGGCCCUG 274 ccuucGGGAGGcGGcccuGdTsdT sense
    207-226 275 CAGGGCCGCCUCCCGAAGG 276 cAGGGCCGCCUCCCGAAGGdTsdT antis
    240-259 277 GCGCGGACCAGCUCGUUCG 278 GcGcGGAccAGcucGuucGdTsdT sense
    240-259 279 CGAACGAGCUGGUCCGCGC 280 CGAACGAGCUGGUCCGCGCdTsdT antis
    242-261 281 GCGGACCAGCUCGUUCGCG 282 GcGGAccAGcucGuucGcGdTsdT sense
    242-261 283 CGCGAACGAGCUGGUCCGC 284 CGCGAACGAGCUGGUCCGCdTsdT antis
    249-268 285 AGCUCGUUCGCGGAGCCAG 286 AGcucGuucGcGGAGccAGdTsdT sense
    249-268 287 CUGGCUCCGCGAACGAGCU 288 CUGGCUCCGCGAACGAGCUdTsdT antis
    252-271 289 UCGUUCGCGGAGCCAGGAG 290 ucGuucGcGGAGccAGGAGdTsdT sense
    252-271 291 CUCCUGGCUCCGCGAACGA 292 CUCCUGGCUCCGCGAACGAdTsdT antis
    324-343 293 GGCACUGGCGGCGGGAAAG 294 GGcAcuGGcGGcGGGAAAGdTsdT sense
    324-343 295 CUUUCCCGCCGCCAGUGCC 296 CUUUCCCGCCGCcAGUGCCdTsdT antis
    329-348 297 UGGCGGCGGGAAAGCGUCA 298 uGGcGGcGGGAAAGcGucAdTsdT sense
    329-348 299 UGACGCUUUCCCGCCGCCA 300 UGACGCUUUCCCGCCGCcAdTsdT antis
    427-446 301 GCCCCGGCGCGGGCACUAG 302 GccccGGcGcGGGcAcuAGdTsdT sense
    427-446 303 CUAGUGCCCGCGCCGGGGC 304 CuAGUGCCCGCGCCGGGGCdTsdT antis
    428-447 305 CCCCGGCGCGGGCACUAGC 306 ccccGGcGcGGGcAcuAGcdTsdT sense
    428-447 307 GCUAGUGCCCGCGCCGGGG 308 GCuAGUGCCCGCGCCGGGGdTsdT antis
    429-448 309 CCCGGCGCGGGCACUAGCU 310 cccGGcGcGGGcAcuAGcudTsdT sense
    429-448 311 AGCUAGUGCCCGCGCCGGG 312 AGCuAGUGCCCGCGCCGGGdTsdT antis
    430-449 313 CCGGCGCGGGCACUAGCUU 314 ccGGcGcGGGcAcuAGcuudTsdT sense
    430-449 315 AAGCUAGUGCCCGCGCCGG 316 AAGCuAGUGCCCGCGCCGGdTsdT antis
    438-457 317 GGCACUAGCUUCCCGCCGC 318 GGcAcuAGcuucccGccGcdTsdT sense
    438-457 319 GCGGCGGGAAGCUAGUGCC 320 GCGGCGGGAAGCuAGUGCCdTsdT antis
    583-602 321 GAGUAGUAUACCAGGCACG 322 GAGuAGuAuAccAGGcAcGdTsdT sense
    583-602 323 CGUGCCUGGUAUACUACUC 324 CGUGCCUGGuAuACuACUCdTsdT antis
    654-673 325 AGGUUCAAGAACCGAGAAC 326 AGGuucAAGAAccGAGAAcdTsdT sense
    654-673 327 GUUCUCGGUUCUUGAACCU 328 GUUCUCGGUUCUUGAACCUdTsdT antis
    667-686 329 GAGAACUGCAGAUUAUGCG 330 GAGAAcuGcAGAuuAuGcGdTsdT sense
    667-686 331 CGCAUAAUCUGCAGUUCUC 332 CGcAuAAUCUGcAGUUCUCdTsdT antis
    928-947 333 AGCCCCAGAAUUUGCUUGU 334 AGccccAGAAuuuGcuuGudTsdT sense
    928-947 335 ACAAGCAAAUUCUGGGGCU 336 AcAAGcAAAUUCUGGGGCUdTsdT antis
     994-1013 337 AGCAGCUGGUUCGGGGGGA 338 AGcAGcuGGuucGGGGGGAdTsdT sense
     994-1013 339 UCCCCCCGAACCAGCUGCU 340 UCCCCCCGAACcAGCUGCUdTsdT antis
    1005-1024 341 CGGGGGGAGCCCAAUGUGU 342 cGGGGGGAGcccAAuGuGudTsdT sense
    1005-1024 343 ACACAUUGGGCUCCCCCCG 344 AcAcAUUGGGCUCCCCCCGdTsdT antis
    1008-1027 345 GGGGAGCCCAAUGUGUCCU 346 GGGGAGcccAAuGuGuccudTsdT sense
    1008-1027 347 AGGACACAUUGGGCUCCCC 348 AGGAcAcAUUGGGCUCCCCdTsdT antis
    1124-1143 349 UGAGCUACUUCUCGGCCAG 350 uGAGcuAcuucucGGccAGdTsdT sense
    1124-1143 351 CUGGCCGAGAAGUAGCUCA 352 CUGGCCGAGAAGuAGCUcAdTsdT antis
    1303-1322 353 CAAAGACACCACCUGAGGC 354 cAAAGAcAccAccuGAGGcdTsdT sense
    1303-1322 355 GCCUCAGGUGGUGUCUUUG 356 GCCUcAGGUGGUGUCUUUGdTsdT antis
    1311-1330 357 CCACCUGAGGCCAUUGCAC 358 ccAccuGAGGccAuuGcAcdTsdT sense
    1311-1330 359 GUGCAAUGGCCUCAGGUGG 360 GUGcAAUGGCCUcAGGUGGdTsdT antis
    1444-1463 361 GCCCGCUUCCCCCCCUGUU 362 GcccGcuucccccccuGuudTsdT sense
    1444-1463 363 AACAGGGGGGGAAGCGGGC 364 AAcAGGGGGGGAAGCGGGCdTsdT antis
    1488-1507 365 AUCCAACCAUCUCUCAAUG 366 AuccAAccAucucucAAuGdTsdT sense
    1488-1507 367 CAUUGAGAGAUGGUUGGAU 368 cAUUGAGAGAUGGUUGGAUdTsdT antis
    1851-1870 369 AUUUUAACUGUUUGUAGGG 370 AuuuuAAcuGuuuGuAGGGdTsdT sense
    1851-1870 371 CCCUACAAACAGUUAAAAU 372 CCCuAcAAAcAGUuAAAAUdTsdT antis
    1852-1871 373 UUUUAACUGUUUGUAGGGG 374 uuuuAAcuGuuuGuAGGGGdTsdT sense
    1852-1871 375 CCCCUACAAACAGUUAAAA 376 CCCCuAcAAAcAGUuAAAAdTsdT antis
    1935-1954 377 CUCCCCCAGGCUACCACUC 378 cucccccAGGcuAccAcucdTsdT sense
    1935-1954 379 GAGUGGUAGCCUGGGGGAG 380 GAGUGGuAGCCUGGGGGAGdTsdT antis
    1975-1994 381 GGUCCCUUGUAAAUAGAAC 382 GGucccuuGuAAAuAGAAcdTsdT sense
    1975-1994 383 GUUCUAUUUACAAGGGACC 384 GUUCuAUUuAcAAGGGACCdTsdT antis
    2029-2048 385 CCCCUGGGUGUAAAUAGAU 386 ccccuGGGuGuAAAuAGAudTsdT sense
    2029-2048 387 AUCUAUUUACACCCAGGGG 388 AUCuAUUuAcACCcAGGGGdTsdT antis
    2033-2052 389 UGGGUGUAAAUAGAUUGUU 390 uGGGuGuAAAuAGAuuGuudTsdT sense
    2033-2052 391 AACAAUCUAUUUACACCCA 392 AAcAAUCuAUUuAcACCcAdTsdT antis
    2062-2081 393 CUUAAAGAAAACGUCAAUU 394 cuuAAAGAAAAcGucAAuudTsdT sense
    2062-2081 395 AAUUGACGUUUUCUUUAAG 396 AAUUGACGUUUUCUUuAAGdTsdT antis
    2063-2082 397 UUAAAGAAAACGUCAAUUC 398 uuAAAGAAAAcGucAAuucdTsdT sense
    2063-2082 399 GAAUUGACGUUUUCUUUAA 400 GAAUUGACGUUUUCUUuAAdTsdT antis
    2078-2097 401 AUUCACACCAUUCAACUUG 402 AuucAcAccAuucAAcuuGdTsdT sense
    2078-2097 403 CAAGUUGAAUGGUGUGAAU 404 cAAGUUGAAUGGUGUGAAUdTsdT antis
    2082-2101 405 ACACCAUUCAACUUGCCCC 406 AcAccAuucAAcuuGccccdTsdT sense
    2082-2101 407 GGGGCAAGUUGAAUGGUGU 408 GGGGcAAGUUGAAUGGUGUdTsdT antis
    2181-2200 409 UCCCUGGUGUCUUAGUUUC 410 ucccuGGuGucuuAGuuucdTsdT sense
    2181-2200 411 GAAACUAAGACACCAGGGA 412 GAAACuAAGAcACcAGGGAdTsdT antis
    2197-2216 413 UUCCACAGUAAGGUUUGCC 414 uuccAcAGuAAGGuuuGccdTsdT sense
    2197-2216 415 GGCAAACCUUACUGUGGAA 416 GGcAAACCUuACUGUGGAAdTsdT antis
    2209-2228 417 GUUUGCCUGUGUACAGACC 418 GuuuGccuGuGuAcAGAccdTsdT sense
    2209-2228 419 GGUCUGUACACAGGCAAAC 420 GGUCUGuAcAcAGGcAAACdTsdT antis
    2232-2251 421 UUCAAUAAAUUAUUGGCAU 422 uucAAuAAAuuAuuGGcAudTsdT sense
    2232-2251 423 AUGCCAAUAAUUUAUUGAA 424 AUGCcAAuAAUUuAUUGAAdTsdT antis
    2235-2254 425 AAUAAAUUAUUGGCAUGAA 426 AAuAAAuuAuuGGcAuGAAdTsdT sense
    2235-2254 427 UUCAUGCCAAUAAUUUAUU 428 UUcAUGCcAAuAAUUuAUUdTsdT antis
    2243-2262 429 AUUGGCAUGAAACCCUUAA 430 AuuGGcAuGAAAcccuuAAdTsdT sense
    2243-2262 431 UUAAGGGUUUCAUGCCAAU 432 UuAAGGGUUUcAUGCcAAUdTsdT antis
    336-355 433 GGGAAAGCGUCAGUCGGGG 434 GGGAAAGcGucAGucGGGGdTsdT sense
    336-355 435 CCCCGACUGACGCUUUCCC 436 CCCCGACUGACGCUUUCCCdTsdT antis
    894-913 437 AUCCACUCCCAAGGUGUGU 438 AuccAcucccAAGGuGuGudTsdT sense
    894-913 439 ACACACCUUGGGAGUGGAU 440 AcAcACCUUGGGAGUGGAUdTsdT antis
    1070-1089 441 AGCCACAGAUUACACCUCG 442 AGccAcAGAuuAcAccucGdTsdT sense
    1070-1089 443 CGAGGUGUAAUCUGUGGCU 444 CGAGGUGuAAUCUGUGGCUdTsdT antis
    1346-1365 445 GGAGUACACGCCAUCCUCA 446 GGAGuAcAcGccAuccucAdTsdT sense
    1346-1365 447 UGAGGAUGGCGUGUACUCC 448 UGAGGAUGGCGUGuACUCCdTsdT antis
    1976-1995 449 GUCCCUUGUAAAUAGAACC 450 GucccuuGuAAAuAGAAccdTsdT sense
    1976-1995 451 GGUUCUAUUUACAAGGGAC 452 GGUUCuAUUuAcAAGGGACdTsdT antis
    1977-1996 453 UCCCUUGUAAAUAGAACCA 454 ucccuuGuAAAuAGAAccAdTsdT sense
    1977-1996 455 UGGUUCUAUUUACAAGGGA 456 UGGUUCuAUUuAcAAGGGAdTsdT antis
    2194-2213 457 AGUUUCCACAGUAAGGUUU 458 AGuuuccAcAGuAAGGuuudTsdT sense
    2194-2213 459 AAACCUUACUGUGGAAACU 460 AAACCUuACUGUGGAAACUdTsdT antis
    1229-1248 461 GAUGAACCCUAACUAUACG 462 GAuGAAcccuAAcuAuAcGdTsdT sense
    1229-1248 463 CGUAUAGUUAGGGUUCAUC 464 CGuAuAGUuAGGGUUcAUCdTsdT antis
    341-360 465 AGCGUCAGUCGGGGCUAUG 466 AGcGucAGucGGGGcuAuGdTsdT sense
    341-360 467 CAUAGCCCCGACUGACGCU 468 cAuAGCCCCGACUGACGCUdTsdT antis
    574-593 469 GCUCAUUCGGAGUAGUAUA 470 GcucAuucGGAGuAGuAuAdTsdT sense
    574-593 471 UAUACUACUCCGAAUGAGC 472 uAuACuACUCCGAAUGAGCdTsdT antis
    578-597 473 AUUCGGAGUAGUAUACCAG 474 AuucGGAGuAGuAuAccAGdTsdT sense
    578-597 475 CUGGUAUACUACUCCGAAU 476 CUGGuAuACuACUCCGAAUdTsdT antis
    672-691 477 CUGCAGAUUAUGCGUAAGC 478 cuGcAGAuuAuGcGuAAGcdTsdT sense
    672-691 479 GCUUACGCAUAAUCUGCAG 480 GCUuACGcAuAAUCUGcAGdTsdT antis
    673-692 481 UGCAGAUUAUGCGUAAGCU 482 uGcAGAuuAuGcGuAAGcudTsdT sense
    673-692 483 AGCUUACGCAUAAUCUGCA 484 AGCUuACGcAuAAUCUGcAdTsdT antis
    674-693 485 GCAGAUUAUGCGUAAGCUG 486 GcAGAuuAuGcGuAAGcuGdTsdT sense
    674-693 487 CAGCUUACGCAUAAUCUGC 488 cAGCUuACGcAuAAUCUGCdTsdT antis
    1433-1452 489 CCCCAACGACCGCCCGCUU 490 ccccAAcGAccGcccGcuudTsdT sense
    1433-1452 491 AAGCGGGCGGUCGUUGGGG 492 AAGCGGGCGGUCGUUGGGGdTsdT antis
    1434-1453 493 CCCAACGACCGCCCGCUUC 494 cccAAcGAccGcccGcuucdTsdT sense
    1434-1453 495 GAAGCGGGCGGUCGUUGGG 496 GAAGCGGGCGGUCGUUGGGdTsdT antis
    1640-1659 497 UGCUACCCUCGCUAGCUCU 498 uGcuAcccucGcuAGcucudTsdT sense
    1640-1659 499 AGAGCUAGCGAGGGUAGCA 500 AGAGCuAGCGAGGGuAGcAdTsdT antis
    458-477 501 GGGAGUGAAGCUGGGCCGU 502 GGGAGuGAAGcuGGGccGudTsdT sense
    458-477 503 ACGGCCCAGCUUCACUCCC 504 ACGGCCcAGCUUcACUCCCdTsdT antis
    459-478 505 GGAGUGAAGCUGGGCCGUG 506 GGAGuGAAGcuGGGccGuGdTsdT sense
    459-478 507 CACGGCCCAGCUUCACUCC 508 cACGGCCcAGCUUcACUCCdTsdT antis
    573-592 509 GGCUCAUUCGGAGUAGUAU 510 GGcucAuucGGAGuAGuAudTsdT sense
    573-592 511 AUACUACUCCGAAUGAGCC 512 AuACuACUCCGAAUGAGCCdTsdT antis
    575-594 513 CUCAUUCGGAGUAGUAUAC 514 cucAuucGGAGuAGuAuAcdTsdT sense
    575-594 515 GUAUACUACUCCGAAUGAG 516 GuAuACuACUCCGAAUGAGdTsdT antis
    576-595 517 UCAUUCGGAGUAGUAUACC 518 ucAuucGGAGuAGuAuAccdTsdT sense
    576-595 519 GGUAUACUACUCCGAAUGA 520 GGuAuACuACUCCGAAUGAdTsdT antis
    577-596 521 CAUUCGGAGUAGUAUACCA 522 cAuucGGAGuAGuAuAccAdTsdT sense
    577-596 523 UGGUAUACUACUCCGAAUG 524 UGGuAuACuACUCCGAAUGdTsdT antis
    579-598 525 UUCGGAGUAGUAUACCAGG 526 uucGGAGuAGuAuAccAGGdTsdT sense
    579-598 527 CCUGGUAUACUACUCCGAA 528 CCUGGuAuACuACUCCGAAdTsdT antis
    671-690 529 ACUGCAGAUUAUGCGUAAG 530 AcuGcAGAuuAuGcGuAAGdTsdT sense
    671-690 531 CUUACGCAUAAUCUGCAGU 532 CUuACGcAuAAUCUGcAGUdTsdT antis
    786-805 533 CCCGAGACGGUGUACCGAG 534 cccGAGAcGGuGuAccGAGdTsdT sense
    786-805 535 CUCGGUACACCGUCUCGGG 536 CUCGGuAcACCGUCUCGGGdTsdT antis
    787-806 537 CCGAGACGGUGUACCGAGU 538 ccGAGAcGGuGuAccGAGudTsdT sense
    787-806 539 ACUCGGUACACCGUCUCGG 540 ACUCGGuAcACCGUCUCGGdTsdT antis
    789-808 541 GAGACGGUGUACCGAGUGG 542 GAGAcGGuGuAccGAGuGGdTsdT sense
    789-808 543 CCACUCGGUACACCGUCUC 544 CcACUCGGuAcACCGUCUCdTsdT antis
    1065-1084 545 UUUGGAGCCACAGAUUACA 546 uuuGGAGccAcAGAuuAcAdTsdT sense
    1065-1084 547 UGUAAUCUGUGGCUCCAAA 548 UGuAAUCUGUGGCUCcAAAdTsdT antis
    1226-1245 549 AGAGAUGAACCCUAACUAU 550 AGAGAuGAAcccuAAcuAudTsdT sense
    1226-1245 551 AUAGUUAGGGUUCAUCUCU 552 AuAGUuAGGGUUcAUCUCUdTsdT antis
    1228-1247 553 AGAUGAACCCUAACUAUAC 554 AGAuGAAcccuAAcuAuAcdTsdT sense
    1228-1247 555 GUAUAGUUAGGGUUCAUCU 556 GuAuAGUuAGGGUUcAUCUdTsdT antis
    1636-1655 557 CAACUGCUACCCUCGCUAG 558 cAAcuGcuAcccucGcuAGdTsdT sense
    1636-1655 559 CUAGCGAGGGUAGCAGUUG 560 CuAGCGAGGGuAGcAGUUGdTsdT antis
    1639-1658 561 CUGCUACCCUCGCUAGCUC 562 cuGcuAcccucGcuAGcucdTsdT sense
    1639-1658 563 GAGCUAGCGAGGGUAGCAG 564 GAGCuAGCGAGGGuAGcAGdTsdT antis
    2036-2055 565 GUGUAAAUAGAUUGUUAUA 566 GuGuAAAuAGAuuGuuAuAdTsdT sense
    2036-2055 567 UAUAACAAUCUAUUUACAC 568 uAuAAcAAUCuAUUuAcACdTsdT antis
    426-445 569 GGCCCCGGCGCGGGCACUA 570 GGccccGGcGcGGGcAcuAdTsdT sense
    426-445 571 UAGUGCCCGCGCCGGGGCC 572 uAGUGCCCGCGCCGGGGCCdTsdT antis
    883-902 573 GCUUGGCCUACAUCCACUC 574 GcuuGGccuAcAuccAcucdTsdT sense
    883-902 575 GAGUGGAUGUAGGCCAAGC 576 GAGUGGAUGuAGGCcAAGCdTsdT antis
    1227-1246 577 GAGAUGAACCCUAACUAUA 578 GAGAuGAAcccuAAcuAuAdTsdT sense
    1227-1246 579 UAUAGUUAGGGUUCAUCUC 580 uAuAGUuAGGGUUcAUCUCdTsdT antis
    1369-1388 581 UCUCCCCACUCGAGGCUUG 582 ucuccccAcucGAGGcuuGdTsdT sense
    1369-1388 583 CAAGCCUCGAGUGGGGAGA 584 cAAGCCUCGAGUGGGGAGAdTsdT antis
    1393-1412 585 ACAGCUUCUUCGAUGAACU 586 AcAGcuucuucGAuGAAcudTsdT sense
    1393-1412 587 AGUUCAUCGAAGAAGCUGU 588 AGUUcAUCGAAGAAGCUGUdTsdT antis
    1431-1450 589 CUCCCCAACGACCGCCCGC 590 cuccccAAcGAccGcccGcdTsdT sense
    1431-1450 591 GCGGGCGGUCGUUGGGGAG 592 GCGGGCGGUCGUUGGGGAGdTsdT antis
    1436-1455 593 CAACGACCGCCCGCUUCCC 594 cAAcGAccGcccGcuucccdTsdT sense
    1436-1455 595 GGGAAGCGGGCGGUCGUUG 596 GGGAAGCGGGCGGUCGUUGdTsdT antis
    1437-1456 597 AACGACCGCCCGCUUCCCC 598 AAcGAccGcccGcuuccccdTsdT sense
    1437-1456 599 GGGGAAGCGGGCGGUCGUU 600 GGGGAAGCGGGCGGUCGUUdTsdT antis
    2176-2195 601 GAGAGUCCCUGGUGUCUUA 602 GAGAGucccuGGuGucuuAdTsdT sense
    2176-2195 603 UAAGACACCAGGGACUCUC 604 uAAGAcACcAGGGACUCUCdTsdT antis
    599-618 605 ACGGCUGGCAGAGACGAGG 606 AcGGcuGGcAGAGAcGAGGdTsdT sense
    599-618 607 CCUCGUCUCUGCCAGCCGU 608 CCUCGUCUCUGCcAGCCGUdTsdT antis
    706-725 609 UUGUGAGGCUGCGGUACUU 610 uuGuGAGGcuGcGGuAcuudTsdT sense
    706-725 611 AAGUACCGCAGCCUCACAA 612 AAGuACCGcAGCCUcAcAAdTsdT antis
    707-726 613 UGUGAGGCUGCGGUACUUU 614 uGuGAGGcuGcGGuAcuuudTsdT sense
    707-726 615 AAAGUACCGCAGCCUCACA 616 AAAGuACCGcAGCCUcAcAdTsdT antis
    791-810 617 GACGGUGUACCGAGUGGCC 618 GAcGGuGuAccGAGuGGccdTsdT sense
    791-810 619 GGCCACUCGGUACACCGUC 620 GGCcACUCGGuAcACCGUCdTsdT antis
    899-918 621 CUCCCAAGGUGUGUGUCAC 622 cucccAAGGuGuGuGucAcdTsdT sense
    899-918 623 GUGACACACACCUUGGGAG 624 GUGAcAcAcACCUUGGGAGdTsdT antis
     989-1008 625 UGCAAAGCAGCUGGUUCGG 626 uGcAAAGcAGcuGGuucGGdTsdT sense
     989-1008 627 CCGAACCAGCUGCUUUGCA 628 CCGAACcAGCUGCUUUGcAdTsdT antis
    1064-1083 629 CUUUGGAGCCACAGAUUAC 630 cuuuGGAGccAcAGAuuAcdTsdT sense
    1064-1083 631 GUAAUCUGUGGCUCCAAAG 632 GuAAUCUGUGGCUCcAAAGdTsdT antis
    1066-1085 633 UUGGAGCCACAGAUUACAC 634 uuGGAGccAcAGAuuAcAcdTsdT sense
    1066-1085 635 GUGUAAUCUGUGGCUCCAA 636 GUGuAAUCUGUGGCUCcAAdTsdT antis
    1125-1144 637 GAGCUACUUCUCGGCCAGC 638 GAGcuAcuucucGGccAGcdTsdT sense
    1125-1144 639 GCUGGCCGAGAAGUAGCUC 640 GCUGGCCGAGAAGuAGCUCdTsdT antis
    1225-1244 641 GAGAGAUGAACCCUAACUA 642 GAGAGAuGAAcccuAAcuAdTsdT sense
    1225-1244 643 UAGUUAGGGUUCAUCUCUC 644 uAGUuAGGGUUcAUCUCUCdTsdT antis
    1265-1284 645 GAUCAAAGCUCACCCUUGG 646 GAucAAAGcucAcccuuGGdTsdT sense
    1265-1284 647 CCAAGGGUGAGCUUUGAUC 648 CcAAGGGUGAGCUUUGAUCdTsdT antis
    1269-1288 649 AAAGCUCACCCUUGGACAA 650 AAAGcucAcccuuGGAcAAdTsdT sense
    1269-1288 651 UUGUCCAAGGGUGAGCUUU 652 UUGUCcAAGGGUGAGCUUUdTsdT antis
    1365-1384 653 AGGCUCUCCCCACUCGAGG 654 AGGcucuccccAcucGAGGdTsdT sense
    1365-1384 655 CCUCGAGUGGGGAGAGCCU 656 CCUCGAGUGGGGAGAGCCUdTsdT antis
    1481-1500 657 ACUGUCCAUCCAACCAUCU 658 AcuGuccAuccAAccAucudTsdT sense
    1481-1500 659 AGAUGGUUGGAUGGACAGU 660 AGAUGGUUGGAUGGAcAGUdTsdT antis
    1637-1656 661 AACUGCUACCCUCGCUAGC 662 AAcuGcuAcccucGcuAGcdTsdT sense
    1637-1656 663 GCUAGCGAGGGUAGCAGUU 664 GCuAGCGAGGGuAGcAGUUdTsdT antis
    1979-1998 665 CCUUGUAAAUAGAACCAGC 666 ccuuGuAAAuAGAAccAGcdTsdT sense
    1979-1998 667 GCUGGUUCUAUUUACAAGG 668 GCUGGUUCuAUUuAcAAGGdTsdT antis
    2196-2215 669 UUUCCACAGUAAGGUUUGC 670 uuuccAcAGuAAGGuuuGcdTsdT sense
    2196-2215 671 GCAAACCUUACUGUGGAAA 672 GcAAACCUuACUGUGGAAAdTsdT antis
    1978-1997 673 CCCUUGUAAAUAGAACCAG 674 cccuuGuAAAuAGAAccAGdTsdT sense
    1978-1997 675 CUGGUUCUAUUUACAAGGG 676 CUGGUUCuAUUuAcAAGGGdTsdT antis
    651-670 677 AAAAGGUUCAAGAACCGAG 678 AAAAGGuucAAGAAccGAGdTsdT sense
    651-670 679 CUCGGUUCUUGAACCUUUU 680 CUCGGUUCUUGAACCUUUUdTsdT antis
    702-721 681 AAUAUUGUGAGGCUGCGGU 682 AAuAuuGuGAGGcuGcGGudTsdT sense
    702-721 683 ACCGCAGCCUCACAAUAUU 684 ACCGcAGCCUcAcAAuAUUdTsdT antis
    1363-1382 685 CAAGGCUCUCCCCACUCGA 686 cAAGGcucuccccAcucGAdTsdT sense
    1363-1382 687 UCGAGUGGGGAGAGCCUUG 688 UCGAGUGGGGAGAGCCUUGdTsdT antis
    701-720 689 CAAUAUUGUGAGGCUGCGG 690 cAAuAuuGuGAGGcuGcGGdTsdT sense
    701-720 691 CCGCAGCCUCACAAUAUUG 692 CCGcAGCCUcAcAAuAUUGdTsdT antis
    1237-1256 693 CUAACUAUACGGAGUUCAA 694 cuAAcuAuAcGGAGuucAAdTsdT sense
    1237-1256 695 UUGAACUCCGUAUAGUUAG 696 UUGAACUCCGuAuAGUuAGdTsdT antis
    2064-2083 697 UAAAGAAAACGUCAAUUCA 698 uAAAGAAAAcGucAAuucAdTsdT sense
    2064-2083 699 UGAAUUGACGUUUUCUUUA 700 UGAAUUGACGUUUUCUUuAdTsdT antis
    828-847 701 AAGCUGAUCACCCCUAUCA 702 AAGcuGAucAccccuAucAdTsdT sense
    828-847 703 UGAUAGGGGUGAUCAGCUU 704 UGAuAGGGGUGAUcAGCUUdTsdT antis
    930-949 705 CCCCAGAAUUUGCUUGUGG 706 ccccAGAAuuuGcuuGuGGdTsdT sense
    930-949 707 CCACAAGCAAAUUCUGGGG 708 CcAcAAGcAAAUUCUGGGGdTsdT antis
     995-1014 709 GCAGCUGGUUCGGGGGGAG 710 GcAGcuGGuucGGGGGGAGdTsdT sense
     995-1014 711 CUCCCCCCGAACCAGCUGC 712 CUCCCCCCGAACcAGCUGCdTsdT antis
    1478-1497 713 UGAACUGUCCAUCCAACCA 714 uGAAcuGuccAuccAAccAdTsdT sense
    1478-1497 715 UGGUUGGAUGGACAGUUCA 716 UGGUUGGAUGGAcAGUUcAdTsdT antis
    1604-1623 717 GACUGGCCAAGAUUGGCAG 718 GAcuGGccAAGAuuGGcAGdTsdT sense
    1604-1623 719 CUGCCAAUCUUGGCCAGUC 720 CUGCcAAUCUUGGCcAGUCdTsdT antis
    1808-1827 721 CUCCCUCAGCAGCCUAACC 722 cucccucAGcAGccuAAccdTsdT sense
    1808-1827 723 GGUUAGGCUGCUGAGGGAG 724 GGUuAGGCUGCUGAGGGAGdTsdT antis
    2177-2196 725 AGAGUCCCUGGUGUCUUAG 726 AGAGucccuGGuGucuuAGdTsdT sense
    2177-2196 727 CUAAGACACCAGGGACUCU 728 CuAAGAcACcAGGGACUCUdTsdT antis
     82-101 729 GAACGGCGCGGCCUGGAAG 730 GAAcGGcGcGGccuGGAAGdTsdT sense
     82-101 731 CUUCCAGGCCGCGCCGUUC 732 CUUCcAGGCCGCGCCGUUCdTsdT antis
    1077-1096 733 GAUUACACCUCGUCCAUCG 734 GAuuAcAccucGuccAucGdTsdT sense
    1077-1096 735 CGAUGGACGAGGUGUAAUC 736 CGAUGGACGAGGUGuAAUCdTsdT antis
    1238-1257 737 UAACUAUACGGAGUUCAAG 738 uAAcuAuAcGGAGuucAAGdTsdT sense
    1238-1257 739 CUUGAACUCCGUAUAGUUA 740 CUUGAACUCCGuAuAGUuAdTsdT antis
    248-267 741 CAGCUCGUUCGCGGAGCCA 742 cAGcucGuucGcGGAGccAdTsdT sense
    248-267 743 UGGCUCCGCGAACGAGCUG 744 UGGCUCCGCGAACGAGCUGdTsdT antis
    250-269 745 GCUCGUUCGCGGAGCCAGG 746 GcucGuucGcGGAGccAGGdTsdT sense
    250-269 747 CCUGGCUCCGCGAACGAGC 748 CCUGGCUCCGCGAACGAGCdTsdT antis
    327-346 749 ACUGGCGGCGGGAAAGCGU 750 AcuGGcGGcGGGAAAGcGudTsdT sense
    327-346 751 ACGCUUUCCCGCCGCCAGU 752 ACGCUUUCCCGCCGCcAGUdTsdT antis
    332-351 753 CGGCGGGAAAGCGUCAGUC 754 cGGcGGGAAAGcGucAGucdTsdT sense
    332-351 755 GACUGACGCUUUCCCGCCG 756 GACUGACGCUUUCCCGCCGdTsdT antis
    376-395 757 CCUCGAGCUCCGGGGGUGG 758 ccucGAGcuccGGGGGuGGdTsdT sense
    376-395 759 CCACCCCCGGAGCUCGAGG 760 CcACCCCCGGAGCUCGAGGdTsdT antis
    468-487 761 CUGGGCCGUGACAGCGGGA 762 cuGGGccGuGAcAGcGGGAdTsdT sense
    468-487 763 UCCCGCUGUCACGGCCCAG 764 UCCCGCUGUcACGGCCcAGdTsdT antis
    584-603 765 AGUAGUAUACCAGGCACGG 766 AGuAGuAuAccAGGcAcGGdTsdT sense
    584-603 767 CCGUGCCUGGUAUACUACU 768 CCGUGCCUGGuAuACuACUdTsdT antis
    785-804 769 GCCCGAGACGGUGUACCGA 770 GcccGAGAcGGuGuAccGAdTsdT sense
    785-804 771 UCGGUACACCGUCUCGGGC 772 UCGGuAcACCGUCUCGGGCdTsdT antis
    1010-1029 773 GGAGCCCAAUGUGUCCUAC 774 GGAGcccAAuGuGuccuAcdTsdT sense
    1010-1029 775 GUAGGACACAUUGGGCUCC 776 GuAGGAcAcAUUGGGCUCCdTsdT antis
    1011-1030 777 GAGCCCAAUGUGUCCUACA 778 GAGcccAAuGuGuccuAcAdTsdT sense
    1011-1030 779 UGUAGGACACAUUGGGCUC 780 UGuAGGAcAcAUUGGGCUCdTsdT antis
    1021-1040 781 UGUCCUACAUCUGCUCUCG 782 uGuccuAcAucuGcucucGdTsdT sense
    1021-1040 783 CGAGAGCAGAUGUAGGACA 784 CGAGAGcAGAUGuAGGAcAdTsdT antis
    1022-1041 785 GUCCUACAUCUGCUCUCGG 786 GuccuAcAucuGcucucGGdTsdT sense
    1022-1041 787 CCGAGAGCAGAUGUAGGAC 788 CCGAGAGcAGAUGuAGGACdTsdT antis
    1023-1042 789 UCCUACAUCUGCUCUCGGU 790 uccuAcAucuGcucucGGudTsdT sense
    1023-1042 791 ACCGAGAGCAGAUGUAGGA 792 ACCGAGAGcAGAUGuAGGAdTsdT antis
    1072-1091 793 CCACAGAUUACACCUCGUC 794 ccAcAGAuuAcAccucGucdTsdT sense
    1072-1091 795 GACGAGGUGUAAUCUGUGG 796 GACGAGGUGuAAUCUGUGGdTsdT antis
    1127-1146 797 GCUACUUCUCGGCCAGCCC 798 GcuAcuucucGGccAGcccdTsdT sense
    1127-1146 799 GGGCUGGCCGAGAAGUAGC 800 GGGCUGGCCGAGAAGuAGCdTsdT antis
    1408-1427 801 AACUGCGGAGACUCGGAGC 802 AAcuGcGGAGAcucGGAGcdTsdT sense
    1408-1427 803 GCUCCGAGUCUCCGCAGUU 804 GCUCCGAGUCUCCGcAGUUdTsdT antis
    1432-1451 805 UCCCCAACGACCGCCCGCU 806 uccccAAcGAccGcccGcudTsdT sense
    1432-1451 807 AGCGGGCGGUCGUUGGGGA 808 AGCGGGCGGUCGUUGGGGAdTsdT antis
    1982-2001 809 UGUAAAUAGAACCAGCCCA 810 uGuAAAuAGAAccAGcccAdTsdT sense
    1982-2001 811 UGGGCUGGUUCUAUUUACA 812 UGGGCUGGUUCuAUUuAcAdTsdT antis
    2030-2049 813 CCCUGGGUGUAAAUAGAUU 814 cccuGGGuGuAAAuAGAuudTsdT sense
    2030-2049 815 AAUCUAUUUACACCCAGGG 816 AAUCuAUUuAcACCcAGGGdTsdT antis
    2073-2092 817 CGUCAAUUCACACCAUUCA 818 cGucAAuucAcAccAuucAdTsdT sense
    2073-2092 819 UGAAUGGUGUGAAUUGACG 820 UGAAUGGUGUGAAUUGACGdTsdT antis
    2218-2237 821 UGUACAGACCUCUGUUCAA 822 uGuAcAGAccucuGuucAAdTsdT sense
    2218-2237 823 UUGAACAGAGGUCUGUACA 824 UUGAAcAGAGGUCUGuAcAdTsdT antis
    2229-2248 825 CUGUUCAAUAAAUUAUUGG 826 cuGuucAAuAAAuuAuuGGdTsdT sense
    2229-2248 827 CCAAUAAUUUAUUGAACAG 828 CcAAuAAUUuAUUGAAcAGdTsdT antis
     7-26 829 ACAACGAAGCCGACGGCAG 830 AcAAcGAAGccGAcGGcAGdTsdT sense
     7-26 831 CUGCCGUCGGCUUCGUUGU 832 CUGCCGUCGGCUUCGUUGUdTsdT antis
     8-27 833 CAACGAAGCCGACGGCAGA 834 cAAcGAAGccGAcGGcAGAdTsdT sense
     8-27 835 UCUGCCGUCGGCUUCGUUG 836 UCUGCCGUCGGCUUCGUUGdTsdT antis
    76-95 837 GAGCCCGAACGGCGCGGCC 838 GAGcccGAAcGGcGcGGccdTsdT sense
    76-95 839 GGCCGCGCCGUUCGGGCUC 840 GGCCGCGCCGUUCGGGCUCdTsdT antis
    176-195 841 GCCUGCGCUCGGCGCCAUG 842 GccuGcGcucGGcGccAuGdTsdT sense
    176-195 843 CAUGGCGCCGAGCGCAGGC 844 cAUGGCGCCGAGCGcAGGCdTsdT antis
    434-453 845 CGCGGGCACUAGCUUCCCG 846 cGcGGGcAcuAGcuucccGdTsdT sense
    434-453 847 CGGGAAGCUAGUGCCCGCG 848 CGGGAAGCuAGUGCCCGCGdTsdT antis
    472-491 849 GCCGUGACAGCGGGAAGGU 850 GccGuGAcAGcGGGAAGGudTsdT sense
    472-491 851 ACCUUCCCGCUGUCACGGC 852 ACCUUCCCGCUGUcACGGCdTsdT antis
    537-556 853 GAAGUGGCUUACACUGACA 854 GAAGuGGcuuAcAcuGAcAdTsdT sense
    537-556 855 UGUCAGUGUAAGCCACUUC 856 UGUcAGUGuAAGCcACUUCdTsdT antis
    656-675 857 GUUCAAGAACCGAGAACUG 858 GuucAAGAAccGAGAAcuGdTsdT sense
    656-675 859 CAGUUCUCGGUUCUUGAAC 860 cAGUUCUCGGUUCUUGAACdTsdT antis
    657-676 861 UUCAAGAACCGAGAACUGC 862 uucAAGAAccGAGAAcuGcdTsdT sense
    657-676 863 GCAGUUCUCGGUUCUUGAA 864 GcAGUUCUCGGUUCUUGAAdTsdT antis
    784-803 865 UGCCCGAGACGGUGUACCG 866 uGcccGAGAcGGuGuAccGdTsdT sense
    784-803 867 CGGUACACCGUCUCGGGCA 868 CGGuAcACCGUCUCGGGcAdTsdT antis
    1404-1423 869 GAUGAACUGCGGAGACUCG 870 GAuGAAcuGcGGAGAcucGdTsdT sense
    1404-1423 871 CGAGUCUCCGCAGUUCAUC 872 CGAGUCUCCGcAGUUcAUCdTsdT antis
    1405-1424 873 AUGAACUGCGGAGACUCGG 874 AuGAAcuGcGGAGAcucGGdTsdT sense
    1405-1424 875 CCGAGUCUCCGCAGUUCAU 876 CCGAGUCUCCGcAGUUcAUdTsdT antis
    1445-1464 877 CCCGCUUCCCCCCCUGUUC 878 cccGcuucccccccuGuucdTsdT sense
    1445-1464 879 GAACAGGGGGGGAAGCGGG 880 GAAcAGGGGGGGAAGCGGGdTsdT antis
    1446-1465 881 CCGCUUCCCCCCCUGUUCA 882 ccGcuucccccccuGuucAdTsdT sense
    1446-1465 883 UGAACAGGGGGGGAAGCGG 884 UGAAcAGGGGGGGAAGCGGdTsdT antis
    1470-1489 885 AGUCCUGGUGAACUGUCCA 886 AGuccuGGuGAAcuGuccAdTsdT sense
    1470-1489 887 UGGACAGUUCACCAGGACU 888 UGGAcAGUUcACcAGGACUdTsdT antis
    1897-1916 889 GGGGGUGUGAGGACCUUCU 890 GGGGGuGuGAGGAccuucudTsdT sense
    1897-1916 891 AGAAGGUCCUCACACCCCC 892 AGAAGGUCCUcAcACCCCCdTsdT antis
    1937-1956 893 CCCCCAGGCUACCACUCCU 894 cccccAGGcuAccAcuccudTsdT sense
    1937-1956 895 AGGAGUGGUAGCCUGGGGG 896 AGGAGUGGuAGCCUGGGGGdTsdT antis
    1981-2000 897 UUGUAAAUAGAACCAGCCC 898 uuGuAAAuAGAAccAGcccdTsdT sense
    1981-2000 899 GGGCUGGUUCUAUUUACAA 900 GGGCUGGUUCuAUUuAcAAdTsdT antis
    1985-2004 901 AAAUAGAACCAGCCCAGCC 902 AAAuAGAAccAGcccAGccdTsdT sense
    1985-2004 903 GGCUGGGCUGGUUCUAUUU 904 GGCUGGGCUGGUUCuAUUUdTsdT antis
    2061-2080 905 UCUUAAAGAAAACGUCAAU 906 ucuuAAAGAAAAcGucAAudTsdT sense
    2061-2080 907 AUUGACGUUUUCUUUAAGA 908 AUUGACGUUUUCUUuAAGAdTsdT antis
    2065-2084 909 AAAGAAAACGUCAAUUCAC 910 AAAGAAAAcGucAAuucAcdTsdT sense
    2065-2084 911 GUGAAUUGACGUUUUCUUU 912 GUGAAUUGACGUUUUCUUUdTsdT antis
     1-20 913 GUGGUGACAACGAAGCCGA 914 GuGGuGAcAAcGAAGccGAdTsdT sense
     1-20 915 UCGGCUUCGUUGUCACCAC 916 UCGGCUUCGUUGUcACcACdTsdT antis
    11-30 917 CGAAGCCGACGGCAGAGGG 918 cGAAGccGAcGGcAGAGGGdTsdT sense
    11-30 919 CCCUCUGCCGUCGGCUUCG 920 CCCUCUGCCGUCGGCUUCGdTsdT antis
    70-89 921 GAGCCGGAGCCCGAACGGC 922 GAGccGGAGcccGAAcGGcdTsdT sense
    70-89 923 GCCGUUCGGGCUCCGGCUC 924 GCCGUUCGGGCUCCGGCUCdTsdT antis
    73-92 925 CCGGAGCCCGAACGGCGCG 926 ccGGAGcccGAAcGGcGcGdTsdT sense
    73-92 927 CGCGCCGUUCGGGCUCCGG 928 CGCGCCGUUCGGGCUCCGGdTsdT antis
    150-169 929 CAGGCAGCCCGAGCCCCGC 930 cAGGcAGcccGAGccccGcdTsdT sense
    150-169 931 GCGGGGCUCGGGCUGCCUG 932 GCGGGGCUCGGGCUGCCUGdTsdT antis
    178-197 933 CUGCGCUCGGCGCCAUGAG 934 cuGcGcucGGcGccAuGAGdTsdT sense
    178-197 935 CUCAUGGCGCCGAGCGCAG 936 CUcAUGGCGCCGAGCGcAGdTsdT antis
    180-199 937 GCGCUCGGCGCCAUGAGCG 938 GcGcucGGcGccAuGAGcGdTsdT sense
    180-199 939 CGCUCAUGGCGCCGAGCGC 940 CGCUcAUGGCGCCGAGCGCdTsdT antis
    196-215 941 GCGGCGGCGGGCCUUCGGG 942 GcGGcGGcGGGccuucGGGdTsdT sense
    196-215 943 CCCGAAGGCCCGCCGCCGC 944 CCCGAAGGCCCGCCGCCGCdTsdT antis
    202-221 945 GCGGGCCUUCGGGAGGCGG 946 GcGGGccuucGGGAGGcGGdTsdT sense
    202-221 947 CCGCCUCCCGAAGGCCCGC 948 CCGCCUCCCGAAGGCCCGCdTsdT antis
    223-242 949 CUGGGGGCUCGGGCCGGGC 950 cuGGGGGcucGGGccGGGcdTsdT sense
    223-242 951 GCCCGGCCCGAGCCCCCAG 952 GCCCGGCCCGAGCCCCcAGdTsdT antis
    238-257 953 GGGCGCGGACCAGCUCGUU 954 GGGcGcGGAccAGcucGuudTsdT sense
    238-257 955 AACGAGCUGGUCCGCGCCC 956 AACGAGCUGGUCCGCGCCCdTsdT antis
    317-336 957 CCCAGGAGGCACUGGCGGC 958 cccAGGAGGcAcuGGcGGcdTsdT sense
    317-336 959 GCCGCCAGUGCCUCCUGGG 960 GCCGCcAGUGCCUCCUGGGdTsdT antis
    337-356 961 GGAAAGCGUCAGUCGGGGC 962 GGAAAGcGucAGucGGGGcdTsdT sense
    337-356 963 GCCCCGACUGACGCUUUCC 964 GCCCCGACUGACGCUUUCCdTsdT antis
    436-455 965 CGGGCACUAGCUUCCCGCC 966 cGGGcAcuAGcuucccGccdTsdT sense
    436-455 967 GGCGGGAAGCUAGUGCCCG 968 GGCGGGAAGCuAGUGCCCGdTsdT antis
    449-468 969 CCCGCCGCCGGGAGUGAAG 970 cccGccGccGGGAGuGAAGdTsdT sense
    449-468 971 CUUCACUCCCGGCGGCGGG 972 CUUcACUCCCGGCGGCGGGdTsdT antis
    464-483 973 GAAGCUGGGCCGUGACAGC 974 GAAGcuGGGccGuGAcAGcdTsdT sense
    464-483 975 GCUGUCACGGCCCAGCUUC 976 GCUGUcACGGCCcAGCUUCdTsdT antis
    534-553 977 CAAGAAGUGGCUUACACUG 978 cAAGAAGuGGcuuAcAcuGdTsdT sense
    534-553 979 CAGUGUAAGCCACUUCUUG 980 cAGUGuAAGCcACUUCUUGdTsdT antis
    535-554 981 AAGAAGUGGCUUACACUGA 982 AAGAAGuGGcuuAcAcuGAdTsdT sense
    535-554 983 UCAGUGUAAGCCACUUCUU 984 UcAGUGuAAGCcACUUCUUdTsdT antis
    536-555 985 AGAAGUGGCUUACACUGAC 986 AGAAGuGGcuuAcAcuGAcdTsdT sense
    536-555 987 GUCAGUGUAAGCCACUUCU 988 GUcAGUGuAAGCcACUUCUdTsdT antis
    821-840 989 CAAGGCCAAGCUGAUCACC 990 cAAGGccAAGcuGAucAccdTsdT sense
    821-840 991 GGUGAUCAGCUUGGCCUUG 992 GGUGAUcAGCUUGGCCUUGdTsdT antis
    826-845 993 CCAAGCUGAUCACCCCUAU 994 ccAAGcuGAucAccccuAudTsdT sense
    826-845 995 AUAGGGGUGAUCAGCUUGG 996 AuAGGGGUGAUcAGCUUGGdTsdT antis
    897-916 997 CACUCCCAAGGUGUGUGUC 998 cAcucccAAGGuGuGuGucdTsdT sense
    897-916 999 GACACACACCUUGGGAGUG 1000 GAcAcAcACCUUGGGAGUGdTsdT antis
    898-917 1001 ACUCCCAAGGUGUGUGUCA 1002 AcucccAAGGuGuGuGucAdTsdT sense
    898-917 1003 UGACACACACCUUGGGAGU 1004 UGAcAcAcACCUUGGGAGUdTsdT antis
     990-1009 1005 GCAAAGCAGCUGGUUCGGG 1006 GcAAAGcAGcuGGuucGGGdTsdT sense
     990-1009 1007 CCCGAACCAGCUGCUUUGC 1008 CCCGAACcAGCUGCUUUGCdTsdT antis
     992-1011 1009 AAAGCAGCUGGUUCGGGGG 1010 AAAGcAGcuGGuucGGGGGdTsdT sense
     992-1011 1011 CCCCCGAACCAGCUGCUUU 1012 CCCCCGAACcAGCUGCUUUdTsdT antis
     996-1015 1013 CAGCUGGUUCGGGGGGAGC 1014 cAGcuGGuucGGGGGGAGcdTsdT sense
     996-1015 1015 GCUCCCCCCGAACCAGCUG 1016 GCUCCCCCCGAACcAGCUGdTsdT antis
    1007-1026 1017 GGGGGAGCCCAAUGUGUCC 1018 GGGGGAGcccAAuGuGuccdTsdT sense
    1007-1026 1019 GGACACAUUGGGCUCCCCC 1020 GGAcAcAUUGGGCUCCCCCdTsdT antis
    1013-1032 1021 GCCCAAUGUGUCCUACAUC 1022 GcccAAuGuGuccuAcAucdTsdT sense
    1013-1032 1023 GAUGUAGGACACAUUGGGC 1024 GAUGuAGGAcAcAUUGGGCdTsdT antis
    1030-1049 1025 UCUGCUCUCGGUACUACCG 1026 ucuGcucucGGuAcuAccGdTsdT sense
    1030-1049 1027 CGGUAGUACCGAGAGCAGA 1028 CGGuAGuACCGAGAGcAGAdTsdT antis
    1104-1123 1029 UCGGCUGGCUGUGUACUUG 1030 ucGGcuGGcuGuGuAcuuGdTsdT sense
    1104-1123 1031 CAAGUACACAGCCAGCCGA 1032 cAAGuAcAcAGCcAGCCGAdTsdT antis
    1109-1128 1033 UGGCUGUGUACUUGCUGAG 1034 uGGcuGuGuAcuuGcuGAGdTsdT sense
    1109-1128 1035 CUCAGCAAGUACACAGCCA 1036 CUcAGcAAGuAcAcAGCcAdTsdT antis
    1120-1139 1037 UUGCUGAGCUACUUCUCGG 1038 uuGcuGAGcuAcuucucGGdTsdT sense
    1120-1139 1039 CCGAGAAGUAGCUCAGCAA 1040 CCGAGAAGuAGCUcAGcAAdTsdT antis
    1122-1141 1041 GCUGAGCUACUUCUCGGCC 1042 GcuGAGcuAcuucucGGccdTsdT sense
    1122-1141 1043 GGCCGAGAAGUAGCUCAGC 1044 GGCCGAGAAGuAGCUcAGCdTsdT antis
    1266-1285 1045 AUCAAAGCUCACCCUUGGA 1046 AucAAAGcucAcccuuGGAdTsdT sense
    1266-1285 1047 UCCAAGGGUGAGCUUUGAU 1048 UCcAAGGGUGAGCUUUGAUdTsdT antis
    1329-1348 1049 CUCUGCUCUAGCCUACUGG 1050 cucuGcucuAGccuAcuGGdTsdT sense
    1329-1348 1051 CCAGUAGGCUAGAGCAGAG 1052 CcAGuAGGCuAGAGcAGAGdTsdT antis
    1343-1362 1053 ACUGGAGUACACGCCAUCC 1054 AcuGGAGuAcAcGccAuccdTsdT sense
    1343-1362 1055 GGAUGGCGUGUACUCCAGU 1056 GGAUGGCGUGuACUCcAGUdTsdT antis
    1364-1383 1057 AAGGCUCUCCCCACUCGAG 1058 AAGGcucuccccAcucGAGdTsdT sense
    1364-1383 1059 CUCGAGUGGGGAGAGCCUU 1060 CUCGAGUGGGGAGAGCCUUdTsdT antis
    1411-1430 1061 UGCGGAGACUCGGAGCCCA 1062 uGcGGAGAcucGGAGcccAdTsdT sense
    1411-1430 1063 UGGGCUCCGAGUCUCCGCA 1064 UGGGCUCCGAGUCUCCGcAdTsdT antis
    1570-1589 1065 ACAACCCAUCCUCACAAGC 1066 AcAAcccAuccucAcAAGcdTsdT sense
    1570-1589 1067 GCUUGUGAGGAUGGGUUGU 1068 GCUUGUGAGGAUGGGUUGUdTsdT antis
    1589-1608 1069 UUUAACUGAAGCUCAGACU 1070 uuuAAcuGAAGcucAGAcudTsdT sense
    1589-1608 1071 AGUCUGAGCUUCAGUUAAA 1072 AGUCUGAGCUUcAGUuAAAdTsdT antis
    1609-1628 1073 GCCAAGAUUGGCAGCCAUC 1074 GccAAGAuuGGcAGccAucdTsdT sense
    1609-1628 1075 GAUGGCUGCCAAUCUUGGC 1076 GAUGGCUGCcAAUCUUGGCdTsdT antis
    1613-1632 1077 AGAUUGGCAGCCAUCUGAU 1078 AGAuuGGcAGccAucuGAudTsdT sense
    1613-1632 1079 AUCAGAUGGCUGCCAAUCU 1080 AUcAGAUGGCUGCcAAUCUdTsdT antis
    1615-1634 1081 AUUGGCAGCCAUCUGAUGC 1082 AuuGGcAGccAucuGAuGcdTsdT sense
    1615-1634 1083 GCAUCAGAUGGCUGCCAAU 1084 GcAUcAGAUGGCUGCcAAUdTsdT antis
    1809-1828 1085 UCCCUCAGCAGCCUAACCU 1086 ucccucAGcAGccuAAccudTsdT sense
    1809-1828 1087 AGGUUAGGCUGCUGAGGGA 1088 AGGUuAGGCUGCUGAGGGAdTsdT antis
    1844-1863 1089 AAAGAGGAUUUUAACUGUU 1090 AAAGAGGAuuuuAAcuGuudTsdT sense
    1844-1863 1091 AACAGUUAAAAUCCUCUUU 1092 AAcAGUuAAAAUCCUCUUUdTsdT antis
    1847-1866 1093 GAGGAUUUUAACUGUUUGU 1094 GAGGAuuuuAAcuGuuuGudTsdT sense
    1847-1866 1095 ACAAACAGUUAAAAUCCUC 1096 AcAAAcAGUuAAAAUCCUCdTsdT antis
    1853-1872 1097 UUUAACUGUUUGUAGGGGA 1098 uuuAAcuGuuuGuAGGGGAdTsdT sense
    1853-1872 1099 UCCCCUACAAACAGUUAAA 1100 UCCCCuAcAAAcAGUuAAAdTsdT antis
    1857-1876 1101 ACUGUUUGUAGGGGAGGGG 1102 AcuGuuuGuAGGGGAGGGGdTsdT sense
    1857-1876 1103 CCCCUCCCCUACAAACAGU 1104 CCCCUCCCCuAcAAAcAGUdTsdT antis
    1896-1915 1105 UGGGGGUGUGAGGACCUUC 1106 uGGGGGuGuGAGGAccuucdTsdT sense
    1896-1915 1107 GAAGGUCCUCACACCCCCA 1108 GAAGGUCCUcAcACCCCcAdTsdT antis
    1936-1955 1109 UCCCCCAGGCUACCACUCC 1110 ucccccAGGcuAccAcuccdTsdT sense
    1936-1955 1111 GGAGUGGUAGCCUGGGGGA 1112 GGAGUGGuAGCCUGGGGGAdTsdT antis
    1967-1986 1113 CUCUCCCAGGUCCCUUGUA 1114 cucucccAGGucccuuGuAdTsdT sense
    1967-1986 1115 UACAAGGGACCUGGGAGAG 1116 uAcAAGGGACCUGGGAGAGdTsdT antis
    1997-2016 1117 CCCAGCCCAUCUCUCGUCU 1118 cccAGcccAucucucGucudTsdT sense
    1997-2016 1119 AGACGAGAGAUGGGCUGGG 1120 AGACGAGAGAUGGGCUGGGdTsdT antis
    2001-2020 1121 GCCCAUCUCUCGUCUUCCC 1122 GcccAucucucGucuucccdTsdT sense
    2001-2020 1123 GGGAAGACGAGAGAUGGGC 1124 GGGAAGACGAGAGAUGGGCdTsdT antis
    2074-2093 1125 GUCAAUUCACACCAUUCAA 1126 GucAAuucAcAccAuucAAdTsdT sense
    2074-2093 1127 UUGAAUGGUGUGAAUUGAC 1128 UUGAAUGGUGUGAAUUGACdTsdT antis
    2093-2112 1129 CUUGCCCCCCCCAGCUGUA 1130 cuuGccccccccAGcuGuAdTsdT sense
    2093-2112 1131 UACAGCUGGGGGGGGCAAG 1132 uAcAGCUGGGGGGGGcAAGdTsdT antis
    2164-2183 1133 GAGGGGAGUAGAGAGAGUC 1134 GAGGGGAGuAGAGAGAGucdTsdT sense
    2164-2183 1135 GACUCUCUCUACUCCCCUC 1136 GACUCUCUCuACUCCCCUCdTsdT antis
    2168-2187 1137 GGAGUAGAGAGAGUCCCUG 1138 GGAGuAGAGAGAGucccuGdTsdT sense
    2168-2187 1139 CAGGGACUCUCUCUACUCC 1140 cAGGGACUCUCUCuACUCCdTsdT antis
    2185-2204 1141 UGGUGUCUUAGUUUCCACA 1142 uGGuGucuuAGuuuccAcAdTsdT sense
    2185-2204 1143 UGUGGAAACUAAGACACCA 1144 UGUGGAAACuAAGAcACcAdTsdT antis
    2191-2210 1145 CUUAGUUUCCACAGUAAGG 1146 cuuAGuuuccAcAGuAAGGdTsdT sense
    2191-2210 1147 CCUUACUGUGGAAACUAAG 1148 CCUuACUGUGGAAACuAAGdTsdT antis
    2202-2221 1149 CAGUAAGGUUUGCCUGUGU 1150 cAGuAAGGuuuGccuGuGudTsdT sense
    2202-2221 1151 ACACAGGCAAACCUUACUG 1152 AcAcAGGcAAACCUuACUGdTsdT antis
    2242-2261 1153 UAUUGGCAUGAAACCCUUA 1154 uAuuGGcAuGAAAcccuuAdTsdT sense
    2242-2261 1155 UAAGGGUUUCAUGCCAAUA 1156 uAAGGGUUUcAUGCcAAuAdTsdT antis
    388-407 1157 GGGGUGGCCCCAGCGGCAG 1158 GGGGuGGccccAGcGGcAGdTsdT sense
    388-407 1159 CUGCCGCUGGGGCCACCCC 1160 CUGCCGCUGGGGCcACCCCdTsdT antis
    425-444 1161 UGGCCCCGGCGCGGGCACU 1162 uGGccccGGcGcGGGcAcudTsdT sense
    425-444 1163 AGUGCCCGCGCCGGGGCCA 1164 AGUGCCCGCGCCGGGGCcAdTsdT antis
    2163-2182 1165 GGAGGGGAGUAGAGAGAGU 1166 GGAGGGGAGuAGAGAGAGudTsdT sense
    2163-2182 1167 ACUCUCUCUACUCCCCUCC 1168 ACUCUCUCuACUCCCCUCCdTsdT antis
     3-22 1169 GGUGACAACGAAGCCGACG 1170 GGuGAcAAcGAAGccGAcGdTsdT sense
     3-22 1171 CGUCGGCUUCGUUGUCACC 1172 CGUCGGCUUCGUUGUcACCdTsdT antis
    12-31 1173 GAAGCCGACGGCAGAGGGA 1174 GAAGccGAcGGcAGAGGGAdTsdT sense
    12-31 1175 UCCCUCUGCCGUCGGCUUC 1176 UCCCUCUGCCGUCGGCUUCdTsdT antis
    72-91 1177 GCCGGAGCCCGAACGGCGC 1178 GccGGAGcccGAAcGGcGcdTsdT sense
    72-91 1179 GCGCCGUUCGGGCUCCGGC 1180 GCGCCGUUCGGGCUCCGGCdTsdT antis
     90-109 1181 CGGCCUGGAAGAGGCCGGA 1182 cGGccuGGAAGAGGccGGAdTsdT sense
     90-109 1183 UCCGGCCUCUUCCAGGCCG 1184 UCCGGCCUCUUCcAGGCCGdTsdT antis
    316-335 1185 GCCCAGGAGGCACUGGCGG 1186 GcccAGGAGGcAcuGGcGGdTsdT sense
    316-335 1187 CCGCCAGUGCCUCCUGGGC 1188 CCGCcAGUGCCUCCUGGGCdTsdT antis
    335-354 1189 CGGGAAAGCGUCAGUCGGG 1190 cGGGAAAGcGucAGucGGGdTsdT sense
    335-354 1191 CCCGACUGACGCUUUCCCG 1192 CCCGACUGACGCUUUCCCGdTsdT antis
    466-485 1193 AGCUGGGCCGUGACAGCGG 1194 AGcuGGGccGuGAcAGcGGdTsdT sense
    466-485 1195 CCGCUGUCACGGCCCAGCU 1196 CCGCUGUcACGGCCcAGCUdTsdT antis
    489-508 1197 GUGACCACAGUGGUAGCCA 1198 GuGAccAcAGuGGuAGccAdTsdT sense
    489-508 1199 UGGCUACCACUGUGGUCAC 1200 UGGCuACcACUGUGGUcACdTsdT antis
    708-727 1201 GUGAGGCUGCGGUACUUUU 1202 GuGAGGcuGcGGuAcuuuudTsdT sense
    708-727 1203 AAAAGUACCGCAGCCUCAC 1204 AAAAGuACCGcAGCCUcACdTsdT antis
    1098-1117 1205 GUGUGGUCGGCUGGCUGUG 1206 GuGuGGucGGcuGGcuGuGdTsdT sense
    1098-1117 1207 CACAGCCAGCCGACCACAC 1208 cAcAGCcAGCCGACcAcACdTsdT antis
    1117-1136 1209 UACUUGCUGAGCUACUUCU 1210 uAcuuGcuGAGcuAcuucudTsdT sense
    1117-1136 1211 AGAAGUAGCUCAGCAAGUA 1212 AGAAGuAGCUcAGcAAGuAdTsdT antis
    1305-1324 1213 AAGACACCACCUGAGGCCA 1214 AAGAcAccAccuGAGGccAdTsdT sense
    1305-1324 1215 UGGCCUCAGGUGGUGUCUU 1216 UGGCCUcAGGUGGUGUCUUdTsdT antis
    1341-1360 1217 CUACUGGAGUACACGCCAU 1218 cuAcuGGAGuAcAcGccAudTsdT sense
    1341-1360 1219 AUGGCGUGUACUCCAGUAG 1220 AUGGCGUGuACUCcAGuAGdTsdT antis
    1345-1364 1221 UGGAGUACACGCCAUCCUC 1222 uGGAGuAcAcGccAuccucdTsdT sense
    1345-1364 1223 GAGGAUGGCGUGUACUCCA 1224 GAGGAUGGCGUGuACUCcAdTsdT antis
    1811-1830 1225 CCUCAGCAGCCUAACCUCU 1226 ccucAGcAGccuAAccucudTsdT sense
    1811-1830 1227 AGAGGUUAGGCUGCUGAGG 1228 AGAGGUuAGGCUGCUGAGGdTsdT antis
    1850-1869 1229 GAUUUUAACUGUUUGUAGG 1230 GAuuuuAAcuGuuuGuAGGdTsdT sense
    1850-1869 1231 CCUACAAACAGUUAAAAUC 1232 CCuAcAAAcAGUuAAAAUCdTsdT antis
    1969-1988 1233 CUCCCAGGUCCCUUGUAAA 1234 cucccAGGucccuuGuAAAdTsdT sense
    1969-1988 1235 UUUACAAGGGACCUGGGAG 1236 UUuAcAAGGGACCUGGGAGdTsdT antis
    2162-2181 1237 AGGAGGGGAGUAGAGAGAG 1238 AGGAGGGGAGuAGAGAGAGdTsdT sense
    2162-2181 1239 CUCUCUCUACUCCCCUCCU 1240 CUCUCUCuACUCCCCUCCUdTsdT antis
    2195-2214 1241 GUUUCCACAGUAAGGUUUG 1242 GuuuccAcAGuAAGGuuuGdTsdT sense
    2195-2214 1243 CAAACCUUACUGUGGAAAC 1244 cAAACCUuACUGUGGAAACdTsdT antis
    1239-1258 1245 AACUAUACGGAGUUCAAGU 1246 AAcuAuAcGGAGuucAAGudTsdT sense
    1239-1258 1247 ACUUGAACUCCGUAUAGUU 1248 ACUUGAACUCCGuAuAGUUdTsdT antis
    1240-1259 1249 ACUAUACGGAGUUCAAGUU 1250 AcuAuAcGGAGuucAAGuudTsdT sense
    1240-1259 1251 AACUUGAACUCCGUAUAGU 1252 AACUUGAACUCCGuAuAGUdTsdT antis
    80-99 1253 CCGAACGGCGCGGCCUGGA 1254 ccGAAcGGcGcGGccuGGAdTsdT sense
    80-99 1255 UCCAGGCCGCGCCGUUCGG 1256 UCcAGGCCGCGCCGUUCGGdTsdT antis
    745-764 1257 AGAAGGACGAGCUGUAUUU 1258 AGAAGGAcGAGcuGuAuuudTsdT sense
    745-764 1259 AAAUACAGCUCGUCCUUCU 1260 AAAuAcAGCUCGUCCUUCUdTsdT antis
    1078-1097 1261 AUUACACCUCGUCCAUCGA 1262 AuuAcAccucGuccAucGAdTsdT sense
    1078-1097 1263 UCGAUGGACGAGGUGUAAU 1264 UCGAUGGACGAGGUGuAAUdTsdT antis
    2071-2090 1265 AACGUCAAUUCACACCAUU 1266 AAcGucAAuucAcAccAuudTsdT sense
    2071-2090 1267 AAUGGUGUGAAUUGACGUU 1268 AAUGGUGUGAAUUGACGUUdTsdT antis
    15-34 1269 GCCGACGGCAGAGGGACUU 1270 GccGAcGGcAGAGGGAcuudTsdT sense
    15-34 1271 AAGUCCCUCUGCCGUCGGC 1272 AAGUCCCUCUGCCGUCGGCdTsdT antis
    77-96 1273 AGCCCGAACGGCGCGGCCU 1274 AGcccGAAcGGcGcGGccudTsdT sense
    77-96 1275 AGGCCGCGCCGUUCGGGCU 1276 AGGCCGCGCCGUUCGGGCUdTsdT antis
    182-201 1277 GCUCGGCGCCAUGAGCGGC 1278 GcucGGcGccAuGAGcGGcdTsdT sense
    182-201 1279 GCCGCUCAUGGCGCCGAGC 1280 GCCGCUcAUGGCGCCGAGCdTsdT antis
    659-678 1281 CAAGAACCGAGAACUGCAG 1282 cAAGAAccGAGAAcuGcAGdTsdT sense
    659-678 1283 CUGCAGUUCUCGGUUCUUG 1284 CUGcAGUUCUCGGUUCUUGdTsdT antis
    788-807 1285 CGAGACGGUGUACCGAGUG 1286 cGAGAcGGuGuAccGAGuGdTsdT sense
    788-807 1287 CACUCGGUACACCGUCUCG 1288 cACUCGGuAcACCGUCUCGdTsdT antis
    1002-1021 1289 GUUCGGGGGGAGCCCAAUG 1290 GuucGGGGGGAGcccAAuGdTsdT sense
    1002-1021 1291 CAUUGGGCUCCCCCCGAAC 1292 cAUUGGGCUCCCCCCGAACdTsdT antis
    1333-1352 1293 GCUCUAGCCUACUGGAGUA 1294 GcucuAGccuAcuGGAGuAdTsdT sense
    1333-1352 1295 UACUCCAGUAGGCUAGAGC 1296 uACUCcAGuAGGCuAGAGCdTsdT antis
    1435-1454 1297 CCAACGACCGCCCGCUUCC 1298 ccAAcGAccGcccGcuuccdTsdT sense
    1435-1454 1299 GGAAGCGGGCGGUCGUUGG 1300 GGAAGCGGGCGGUCGUUGGdTsdT antis
    2246-2265 1301 GGCAUGAAACCCUUAAAAA 1302 GGcAuGAAAcccuuAAAAAdTsdT sense
    2246-2265 1303 UUUUUAAGGGUUUCAUGCC 1304 UUUUuAAGGGUUUcAUGCCdTsdT antis
    14-33 1305 AGCCGACGGCAGAGGGACU 1306 AGccGAcGGcAGAGGGAcudTsdT sense
    14-33 1307 AGUCCCUCUGCCGUCGGCU 1308 AGUCCCUCUGCCGUCGGCUdTsdT antis
    17-36 1309 CGACGGCAGAGGGACUUCA 1310 cGAcGGcAGAGGGAcuucAdTsdT sense
    17-36 1311 UGAAGUCCCUCUGCCGUCG 1312 UGAAGUCCCUCUGCCGUCGdTsdT antis
    18-37 1313 GACGGCAGAGGGACUUCAU 1314 GAcGGcAGAGGGAcuucAudTsdT sense
    18-37 1315 AUGAAGUCCCUCUGCCGUC 1316 AUGAAGUCCCUCUGCCGUCdTsdT antis
    78-97 1317 GCCCGAACGGCGCGGCCUG 1318 GcccGAAcGGcGcGGccuGdTsdT sense
    78-97 1319 CAGGCCGCGCCGUUCGGGC 1320 cAGGCCGCGCCGUUCGGGCdTsdT antis
     81-100 1321 CGAACGGCGCGGCCUGGAA 1322 cGAAcGGcGcGGccuGGAAdTsdT sense
     81-100 1323 UUCCAGGCCGCGCCGUUCG 1324 UUCcAGGCCGCGCCGUUCGdTsdT antis
     83-102 1325 AACGGCGCGGCCUGGAAGA 1326 AAcGGcGcGGccuGGAAGAdTsdT sense
     83-102 1327 UCUUCCAGGCCGCGCCGUU 1328 UCUUCcAGGCCGCGCCGUUdTsdT antis
     87-106 1329 GCGCGGCCUGGAAGAGGCC 1330 GcGcGGccuGGAAGAGGccdTsdT sense
     87-106 1331 GGCCUCUUCCAGGCCGCGC 1332 GGCCUCUUCcAGGCCGCGCdTsdT antis
    181-200 1333 CGCUCGGCGCCAUGAGCGG 1334 cGcucGGcGccAuGAGcGGdTsdT sense
    181-200 1335 CCGCUCAUGGCGCCGAGCG 1336 CCGCUcAUGGCGCCGAGCGdTsdT antis
    183-202 1337 CUCGGCGCCAUGAGCGGCG 1338 cucGGcGccAuGAGcGGcGdTsdT sense
    183-202 1339 CGCCGCUCAUGGCGCCGAG 1340 CGCCGCUcAUGGCGCCGAGdTsdT antis
    189-208 1341 GCCAUGAGCGGCGGCGGGC 1342 GccAuGAGcGGcGGcGGGcdTsdT sense
    189-208 1343 GCCCGCCGCCGCUCAUGGC 1344 GCCCGCCGCCGCUcAUGGCdTsdT antis
    191-210 1345 CAUGAGCGGCGGCGGGCCU 1346 cAuGAGcGGcGGcGGGccudTsdT sense
    191-210 1347 AGGCCCGCCGCCGCUCAUG 1348 AGGCCCGCCGCCGCUcAUGdTsdT antis
    254-273 1349 GUUCGCGGAGCCAGGAGGC 1350 GuucGcGGAGccAGGAGGcdTsdT sense
    254-273 1351 GCCUCCUGGCUCCGCGAAC 1352 GCCUCCUGGCUCCGCGAACdTsdT antis
    255-274 1353 UUCGCGGAGCCAGGAGGCG 1354 uucGcGGAGccAGGAGGcGdTsdT sense
    255-274 1355 CGCCUCCUGGCUCCGCGAA 1356 CGCCUCCUGGCUCCGCGAAdTsdT antis
    431-450 1357 CGGCGCGGGCACUAGCUUC 1358 cGGcGcGGGcAcuAGcuucdTsdT sense
    431-450 1359 GAAGCUAGUGCCCGCGCCG 1360 GAAGCuAGUGCCCGCGCCGdTsdT antis
    433-452 1361 GCGCGGGCACUAGCUUCCC 1362 GcGcGGGcAcuAGcuucccdTsdT sense
    433-452 1363 GGGAAGCUAGUGCCCGCGC 1364 GGGAAGCuAGUGCCCGCGCdTsdT antis
    441-460 1365 ACUAGCUUCCCGCCGCCGG 1366 AcuAGcuucccGccGccGGdTsdT sense
    441-460 1367 CCGGCGGCGGGAAGCUAGU 1368 CCGGCGGCGGGAAGCuAGUdTsdT antis
    442-461 1369 CUAGCUUCCCGCCGCCGGG 1370 cuAGcuucccGccGccGGGdTsdT sense
    442-461 1371 CCCGGCGGCGGGAAGCUAG 1372 CCCGGCGGCGGGAAGCuAGdTsdT antis
    446-465 1373 CUUCCCGCCGCCGGGAGUG 1374 cuucccGccGccGGGAGuGdTsdT sense
    446-465 1375 CACUCCCGGCGGCGGGAAG 1376 cACUCCCGGCGGCGGGAAGdTsdT antis
    473-492 1377 CCGUGACAGCGGGAAGGUG 1378 ccGuGAcAGcGGGAAGGuGdTsdT sense
    473-492 1379 CACCUUCCCGCUGUCACGG 1380 cACCUUCCCGCUGUcACGGdTsdT antis
    532-551 1381 CCCAAGAAGUGGCUUACAC 1382 cccAAGAAGuGGcuuAcAcdTsdT sense
    532-551 1383 GUGUAAGCCACUUCUUGGG 1384 GUGuAAGCcACUUCUUGGGdTsdT antis
    580-599 1385 UCGGAGUAGUAUACCAGGC 1386 ucGGAGuAGuAuAccAGGcdTsdT sense
    580-599 1387 GCCUGGUAUACUACUCCGA 1388 GCCUGGuAuACuACUCCGAdTsdT antis
    589-608 1389 UAUACCAGGCACGGCUGGC 1390 uAuAccAGGcAcGGcuGGcdTsdT sense
    589-608 1391 GCCAGCCGUGCCUGGUAUA 1392 GCcAGCCGUGCCUGGuAuAdTsdT antis
    598-617 1393 CACGGCUGGCAGAGACGAG 1394 cAcGGcuGGcAGAGAcGAGdTsdT sense
    598-617 1395 CUCGUCUCUGCCAGCCGUG 1396 CUCGUCUCUGCcAGCCGUGdTsdT antis
    837-856 1397 ACCCCUAUCAUCUACAUCA 1398 AccccuAucAucuAcAucAdTsdT sense
    837-856 1399 UGAUGUAGAUGAUAGGGGU 1400 UGAUGuAGAUGAuAGGGGUdTsdT antis
    838-857 1401 CCCCUAUCAUCUACAUCAA 1402 ccccuAucAucuAcAucAAdTsdT sense
    838-857 1403 UUGAUGUAGAUGAUAGGGG 1404 UUGAUGuAGAUGAuAGGGGdTsdT antis
    839-858 1405 CCCUAUCAUCUACAUCAAG 1406 cccuAucAucuAcAucAAGdTsdT sense
    839-858 1407 CUUGAUGUAGAUGAUAGGG 1408 CUUGAUGuAGAUGAuAGGGdTsdT antis
    922-941 1409 ACAUCAAGCCCCAGAAUUU 1410 AcAucAAGccccAGAAuuudTsdT sense
    922-941 1411 AAAUUCUGGGGCUUGAUGU 1412 AAAUUCUGGGGCUUGAUGUdTsdT antis
    923-942 1413 CAUCAAGCCCCAGAAUUUG 1414 cAucAAGccccAGAAuuuGdTsdT sense
    923-942 1415 CAAAUUCUGGGGCUUGAUG 1416 cAAAUUCUGGGGCUUGAUGdTsdT antis
    1012-1031 1417 AGCCCAAUGUGUCCUACAU 1418 AGcccAAuGuGuccuAcAudTsdT sense
    1012-1031 1419 AUGUAGGACACAUUGGGCU 1420 AUGuAGGAcAcAUUGGGCUdTsdT antis
    1014-1033 1421 CCCAAUGUGUCCUACAUCU 1422 cccAAuGuGuccuAcAucudTsdT sense
    1014-1033 1423 AGAUGUAGGACACAUUGGG 1424 AGAUGuAGGAcAcAUUGGGdTsdT antis
    1046-1065 1425 CCGUGCUCCAGAACUCAUC 1426 ccGuGcuccAGAAcucAucdTsdT sense
    1046-1065 1427 GAUGAGUUCUGGAGCACGG 1428 GAUGAGUUCUGGAGcACGGdTsdT antis
    1056-1075 1429 GAACUCAUCUUUGGAGCCA 1430 GAAcucAucuuuGGAGccAdTsdT sense
    1056-1075 1431 UGGCUCCAAAGAUGAGUUC 1432 UGGCUCcAAAGAUGAGUUCdTsdT antis
    1088-1107 1433 GUCCAUCGAUGUGUGGUCG 1434 GuccAucGAuGuGuGGucGdTsdT sense
    1088-1107 1435 CGACCACACAUCGAUGGAC 1436 CGACcAcAcAUCGAUGGACdTsdT antis
    1123-1142 1437 CUGAGCUACUUCUCGGCCA 1438 cuGAGcuAcuucucGGccAdTsdT sense
    1123-1142 1439 UGGCCGAGAAGUAGCUCAG 1440 UGGCCGAGAAGuAGCUcAGdTsdT antis
    1232-1251 1441 GAACCCUAACUAUACGGAG 1442 GAAcccuAAcuAuAcGGAGdTsdT sense
    1232-1251 1443 CUCCGUAUAGUUAGGGUUC 1444 CUCCGuAuAGUuAGGGUUCdTsdT antis
    1287-1306 1445 AAGGUGUUCAAAUCUUCAA 1446 AAGGuGuucAAAucuucAAdTsdT sense
    1287-1306 1447 UUGAAGAUUUGAACACCUU 1448 UUGAAGAUUUGAAcACCUUdTsdT antis
    1319-1338 1449 GGCCAUUGCACUCUGCUCU 1450 GGccAuuGcAcucuGcucudTsdT sense
    1319-1338 1451 AGAGCAGAGUGCAAUGGCC 1452 AGAGcAGAGUGcAAUGGCCdTsdT antis
    1349-1368 1453 GUACACGCCAUCCUCAAGG 1454 GuAcAcGccAuccucAAGGdTsdT sense
    1349-1368 1455 CCUUGAGGAUGGCGUGUAC 1456 CCUUGAGGAUGGCGUGuACdTsdT antis
    1409-1428 1457 ACUGCGGAGACUCGGAGCC 1458 AcuGcGGAGAcucGGAGccdTsdT sense
    1409-1428 1459 GGCUCCGAGUCUCCGCAGU 1460 GGCUCCGAGUCUCCGcAGUdTsdT antis
    1410-1429 1461 CUGCGGAGACUCGGAGCCC 1462 cuGcGGAGAcucGGAGcccdTsdT sense
    1410-1429 1463 GGGCUCCGAGUCUCCGCAG 1464 GGGCUCCGAGUCUCCGcAGdTsdT antis
    1448-1467 1465 GCUUCCCCCCCUGUUCAAC 1466 GcuucccccccuGuucAAcdTsdT sense
    1448-1467 1467 GUUGAACAGGGGGGGAAGC 1468 GUUGAAcAGGGGGGGAAGCdTsdT antis
    1449-1468 1469 CUUCCCCCCCUGUUCAACU 1470 cuucccccccuGuucAAcudTsdT sense
    1449-1468 1471 AGUUGAACAGGGGGGGAAG 1472 AGUUGAAcAGGGGGGGAAGdTsdT antis
    1450-1469 1473 UUCCCCCCCUGUUCAACUU 1474 uucccccccuGuucAAcuudTsdT sense
    1450-1469 1475 AAGUUGAACAGGGGGGGAA 1476 AAGUUGAAcAGGGGGGGAAdTsdT antis
    1567-1586 1477 CCUACAACCCAUCCUCACA 1478 ccuAcAAcccAuccucAcAdTsdT sense
    1567-1586 1479 UGUGAGGAUGGGUUGUAGG 1480 UGUGAGGAUGGGUUGuAGGdTsdT antis
    1583-1602 1481 ACAAGCUUUAACUGAAGCU 1482 AcAAGcuuuAAcuGAAGcudTsdT sense
    1583-1602 1483 AGCUUCAGUUAAAGCUUGU 1484 AGCUUcAGUuAAAGCUUGUdTsdT antis
    1596-1615 1485 GAAGCUCAGACUGGCCAAG 1486 GAAGcucAGAcuGGccAAGdTsdT sense
    1596-1615 1487 CUUGGCCAGUCUGAGCUUC 1488 CUUGGCcAGUCUGAGCUUCdTsdT antis
    1608-1627 1489 GGCCAAGAUUGGCAGCCAU 1490 GGccAAGAuuGGcAGccAudTsdT sense
    1608-1627 1491 AUGGCUGCCAAUCUUGGCC 1492 AUGGCUGCcAAUCUUGGCCdTsdT antis
    1638-1657 1493 ACUGCUACCCUCGCUAGCU 1494 AcuGcuAcccucGcuAGcudTsdT sense
    1638-1657 1495 AGCUAGCGAGGGUAGCAGU 1496 AGCuAGCGAGGGuAGcAGUdTsdT antis
    1854-1873 1497 UUAACUGUUUGUAGGGGAG 1498 uuAAcuGuuuGuAGGGGAGdTsdT sense
    1854-1873 1499 CUCCCCUACAAACAGUUAA 1500 CUCCCCuAcAAAcAGUuAAdTsdT antis
    1980-1999 1501 CUUGUAAAUAGAACCAGCC 1502 cuuGuAAAuAGAAccAGccdTsdT sense
    1980-1999 1503 GGCUGGUUCUAUUUACAAG 1504 GGCUGGUUCuAUUuAcAAGdTsdT antis
    2034-2053 1505 GGGUGUAAAUAGAUUGUUA 1506 GGGuGuAAAuAGAuuGuuAdTsdT sense
    2034-2053 1507 UAACAAUCUAUUUACACCC 1508 uAAcAAUCuAUUuAcACCCdTsdT antis
    2037-2056 1509 UGUAAAUAGAUUGUUAUAA 1510 uGuAAAuAGAuuGuuAuAAdTsdT sense
    2037-2056 1511 UUAUAACAAUCUAUUUACA 1512 UuAuAAcAAUCuAUUuAcAdTsdT antis
    2087-2106 1513 AUUCAACUUGCCCCCCCCA 1514 AuucAAcuuGccccccccAdTsdT sense
    2087-2106 1515 UGGGGGGGGCAAGUUGAAU 1516 UGGGGGGGGcAAGUUGAAUdTsdT antis
    2088-2107 1517 UUCAACUUGCCCCCCCCAG 1518 uucAAcuuGccccccccAGdTsdT sense
    2088-2107 1519 CUGGGGGGGGCAAGUUGAA 1520 CUGGGGGGGGcAAGUUGAAdTsdT antis
    2171-2190 1521 GUAGAGAGAGUCCCUGGUG 1522 GuAGAGAGAGucccuGGuGdTsdT sense
    2171-2190 1523 CACCAGGGACUCUCUCUAC 1524 cACcAGGGACUCUCUCuACdTsdT antis
    2212-2231 1525 UGCCUGUGUACAGACCUCU 1526 uGccuGuGuAcAGAccucudTsdT sense
    2212-2231 1527 AGAGGUCUGUACACAGGCA 1528 AGAGGUCUGuAcAcAGGcAdTsdT antis
    2221-2240 1529 ACAGACCUCUGUUCAAUAA 1530 AcAGAccucuGuucAAuAAdTsdT sense
    2221-2240 1531 UUAUUGAACAGAGGUCUGU 1532 UuAUUGAAcAGAGGUCUGUdTsdT antis
    190-209 1533 CCAUGAGCGGCGGCGGGCC 1534 ccAuGAGcGGcGGcGGGccdTsdT sense
    190-209 1535 GGCCCGCCGCCGCUCAUGG 1536 GGCCCGCCGCCGCUcAUGGdTsdT antis
    377-396 1537 CUCGAGCUCCGGGGGUGGC 1538 cucGAGcuccGGGGGuGGcdTsdT sense
    377-396 1539 GCCACCCCCGGAGCUCGAG 1540 GCcACCCCCGGAGCUCGAGdTsdT antis
    469-488 1541 UGGGCCGUGACAGCGGGAA 1542 uGGGccGuGAcAGcGGGAAdTsdT sense
    469-488 1543 UUCCCGCUGUCACGGCCCA 1544 UUCCCGCUGUcACGGCCcAdTsdT antis
    590-609 1545 AUACCAGGCACGGCUGGCA 1546 AuAccAGGcAcGGcuGGcAdTsdT sense
    590-609 1547 UGCCAGCCGUGCCUGGUAU 1548 UGCcAGCCGUGCCUGGuAUdTsdT antis
    658-677 1549 UCAAGAACCGAGAACUGCA 1550 ucAAGAAccGAGAAcuGcAdTsdT sense
    658-677 1551 UGCAGUUCUCGGUUCUUGA 1552 UGcAGUUCUCGGUUCUUGAdTsdT antis
    998-1017 1553 GCUGGUUCGGGGGGAGCCC 1554 GcuGGuucGGGGGGAGcccdTsdT sense
    998-1017 1555 GGGCUCCCCCCGAACCAGC 1556 GGGCUCCCCCCGAACcAGCdTsdT antis
    999-1018 1557 CUGGUUCGGGGGGAGCCCA 1558 cuGGuucGGGGGGAGcccAdTsdT sense
    999-1018 1559 UGGGCUCCCCCCGAACCAG 1560 UGGGCUCCCCCCGAACcAGdTsdT antis
    1025-1044 1561 CUACAUCUGCUCUCGGUAC 1562 cuAcAucuGcucucGGuAcdTsdT sense
    1025-1044 1563 GUACCGAGAGCAGAUGUAG 1564 GuACCGAGAGcAGAUGuAGdTsdT antis
    1327-1346 1565 CACUCUGCUCUAGCCUACU 1566 cAcucuGcucuAGccuAcudTsdT sense
    1327-1346 1567 AGUAGGCUAGAGCAGAGUG 1568 AGuAGGCuAGAGcAGAGUGdTsdT antis
    1417-1436 1569 GACUCGGAGCCCAGCUCCC 1570 GAcucGGAGcccAGcucccdTsdT sense
    1417-1436 1571 GGGAGCUGGGCUCCGAGUC 1572 GGGAGCUGGGCUCCGAGUCdTsdT antis
    1594-1613 1573 CUGAAGCUCAGACUGGCCA 1574 cuGAAGcucAGAcuGGccAdTsdT sense
    1594-1613 1575 UGGCCAGUCUGAGCUUCAG 1576 UGGCcAGUCUGAGCUUcAGdTsdT antis
    2213-2232 1577 GCCUGUGUACAGACCUCUG 1578 GccuGuGuAcAGAccucuGdTsdT sense
    2213-2232 1579 CAGAGGUCUGUACACAGGC 1580 cAGAGGUCUGuAcAcAGGCdTsdT antis
    1451-1470 1581 UCCCCCCCUGUUCAACUUC 1582 ucccccccuGuucAAcuucdTsdT sense
    1451-1470 1583 GAAGUUGAACAGGGGGGGA 1584 GAAGUUGAAcAGGGGGGGAdTsdT antis
    1563-1582 1585 ACUUCCUACAACCCAUCCU 1586 AcuuccuAcAAcccAuccudTsdT sense
    1563-1582 1587 AGGAUGGGUUGUAGGAAGU 1588 AGGAUGGGUUGuAGGAAGUdTsdT antis
    1607-1626 1589 UGGCCAAGAUUGGCAGCCA 1590 uGGccAAGAuuGGcAGccAdTsdT sense
    1607-1626 1591 UGGCUGCCAAUCUUGGCCA 1592 UGGCUGCcAAUCUUGGCcAdTsdT antis
    1939-1958 1593 CCCAGGCUACCACUCCUUC 1594 cccAGGcuAccAcuccuucdTsdT sense
    1939-1958 1595 GAAGGAGUGGUAGCCUGGG 1596 GAAGGAGUGGuAGCCUGGGdTsdT antis
    74-93 1597 CGGAGCCCGAACGGCGCGG 1598 cGGAGcccGAAcGGcGcGGdTsdT sense
    74-93 1599 CCGCGCCGUUCGGGCUCCG 1600 CCGCGCCGUUCGGGCUCCGdTsdT antis
    75-94 1601 GGAGCCCGAACGGCGCGGC 1602 GGAGcccGAAcGGcGcGGcdTsdT sense
    75-94 1603 GCCGCGCCGUUCGGGCUCC 1604 GCCGCGCCGUUCGGGCUCCdTsdT antis
     85-104 1605 CGGCGCGGCCUGGAAGAGG 1606 cGGcGcGGccuGGAAGAGGdTsdT sense
     85-104 1607 CCUCUUCCAGGCCGCGCCG 1608 CCUCUUCcAGGCCGCGCCGdTsdT antis
     86-105 1609 GGCGCGGCCUGGAAGAGGC 1610 GGcGcGGccuGGAAGAGGcdTsdT sense
     86-105 1611 GCCUCUUCCAGGCCGCGCC 1612 GCCUCUUCcAGGCCGCGCCdTsdT antis
    203-222 1613 CGGGCCUUCGGGAGGCGGC 1614 cGGGccuucGGGAGGcGGcdTsdT sense
    203-222 1615 GCCGCCUCCCGAAGGCCCG 1616 GCCGCCUCCCGAAGGCCCGdTsdT antis
    206-225 1617 GCCUUCGGGAGGCGGCCCU 1618 GccuucGGGAGGcGGcccudTsdT sense
    206-225 1619 AGGGCCGCCUCCCGAAGGC 1620 AGGGCCGCCUCCCGAAGGCdTsdT antis
    208-227 1621 CUUCGGGAGGCGGCCCUGG 1622 cuucGGGAGGcGGcccuGGdTsdT sense
    208-227 1623 CCAGGGCCGCCUCCCGAAG 1624 CcAGGGCCGCCUCCCGAAGdTsdT antis
    245-264 1625 GACCAGCUCGUUCGCGGAG 1626 GAccAGcucGuucGcGGAGdTsdT sense
    245-264 1627 CUCCGCGAACGAGCUGGUC 1628 CUCCGCGAACGAGCUGGUCdTsdT antis
    448-467 1629 UCCCGCCGCCGGGAGUGAA 1630 ucccGccGccGGGAGuGAAdTsdT sense
    448-467 1631 UUCACUCCCGGCGGCGGGA 1632 UUcACUCCCGGCGGCGGGAdTsdT antis
    452-471 1633 GCCGCCGGGAGUGAAGCUG 1634 GccGccGGGAGuGAAGcuGdTsdT sense
    452-471 1635 CAGCUUCACUCCCGGCGGC 1636 cAGCUUcACUCCCGGCGGCdTsdT antis
    453-472 1637 CCGCCGGGAGUGAAGCUGG 1638 ccGccGGGAGuGAAGcuGGdTsdT sense
    453-472 1639 CCAGCUUCACUCCCGGCGG 1640 CcAGCUUcACUCCCGGCGGdTsdT antis
    470-489 1641 GGGCCGUGACAGCGGGAAG 1642 GGGccGuGAcAGcGGGAAGdTsdT sense
    470-489 1643 CUUCCCGCUGUCACGGCCC 1644 CUUCCCGCUGUcACGGCCCdTsdT antis
    588-607 1645 GUAUACCAGGCACGGCUGG 1646 GuAuAccAGGcAcGGcuGGdTsdT sense
    588-607 1647 CCAGCCGUGCCUGGUAUAC 1648 CcAGCCGUGCCUGGuAuACdTsdT antis
    609-628 1649 GAGACGAGGGAACUGGUGG 1650 GAGAcGAGGGAAcuGGuGGdTsdT sense
    609-628 1651 CCACCAGUUCCCUCGUCUC 1652 CcACcAGUUCCCUCGUCUCdTsdT antis
    611-630 1653 GACGAGGGAACUGGUGGCC 1654 GAcGAGGGAAcuGGuGGccdTsdT sense
    611-630 1655 GGCCACCAGUUCCCUCGUC 1656 GGCcACcAGUUCCCUCGUCdTsdT antis
    649-668 1657 ACAAAAGGUUCAAGAACCG 1658 AcAAAAGGuucAAGAAccGdTsdT sense
    649-668 1659 CGGUUCUUGAACCUUUUGU 1660 CGGUUCUUGAACCUUUUGUdTsdT antis
    652-671 1661 AAAGGUUCAAGAACCGAGA 1662 AAAGGuucAAGAAccGAGAdTsdT sense
    652-671 1663 UCUCGGUUCUUGAACCUUU 1664 UCUCGGUUCUUGAACCUUUdTsdT antis
    653-672 1665 AAGGUUCAAGAACCGAGAA 1666 AAGGuucAAGAAccGAGAAdTsdT sense
    653-672 1667 UUCUCGGUUCUUGAACCUU 1668 UUCUCGGUUCUUGAACCUUdTsdT antis
    742-761 1669 AGAAGAAGGACGAGCUGUA 1670 AGAAGAAGGAcGAGcuGuAdTsdT sense
    742-761 1671 UACAGCUCGUCCUUCUUCU 1672 uAcAGCUCGUCCUUCUUCUdTsdT antis
    744-763 1673 AAGAAGGACGAGCUGUAUU 1674 AAGAAGGAcGAGcuGuAuudTsdT sense
    744-763 1675 AAUACAGCUCGUCCUUCUU 1676 AAuAcAGCUCGUCCUUCUUdTsdT antis
    790-809 1677 AGACGGUGUACCGAGUGGC 1678 AGAcGGuGuAccGAGuGGcdTsdT sense
    790-809 1679 GCCACUCGGUACACCGUCU 1680 GCcACUCGGuAcACCGUCUdTsdT antis
    840-859 1681 CCUAUCAUCUACAUCAAGG 1682 ccuAucAucuAcAucAAGGdTsdT sense
    840-859 1683 CCUUGAUGUAGAUGAUAGG 1684 CCUUGAUGuAGAUGAuAGGdTsdT antis
    882-901 1685 AGCUUGGCCUACAUCCACU 1686 AGcuuGGccuAcAuccAcudTsdT sense
    882-901 1687 AGUGGAUGUAGGCCAAGCU 1688 AGUGGAUGuAGGCcAAGCUdTsdT antis
    912-931 1689 UGUCACCGUGACAUCAAGC 1690 uGucAccGuGAcAucAAGcdTsdT sense
    912-931 1691 GCUUGAUGUCACGGUGACA 1692 GCUUGAUGUcACGGUGAcAdTsdT antis
    947-966 1693 GGACCCUGACACUGCUGUC 1694 GGAcccuGAcAcuGcuGucdTsdT sense
    947-966 1695 GACAGCAGUGUCAGGGUCC 1696 GAcAGcAGUGUcAGGGUCCdTsdT antis
    1009-1028 1697 GGGAGCCCAAUGUGUCCUA 1698 GGGAGcccAAuGuGuccuAdTsdT sense
    1009-1028 1699 UAGGACACAUUGGGCUCCC 1700 uAGGAcAcAUUGGGCUCCCdTsdT antis
    1017-1036 1701 AAUGUGUCCUACAUCUGCU 1702 AAuGuGuccuAcAucuGcudTsdT sense
    1017-1036 1703 AGCAGAUGUAGGACACAUU 1704 AGcAGAUGuAGGAcAcAUUdTsdT antis
    1113-1132 1705 UGUGUACUUGCUGAGCUAC 1706 uGuGuAcuuGcuGAGcuAcdTsdT sense
    1113-1132 1707 GUAGCUCAGCAAGUACACA 1708 GuAGCUcAGcAAGuAcAcAdTsdT antis
    1121-1140 1709 UGCUGAGCUACUUCUCGGC 1710 uGcuGAGcuAcuucucGGcdTsdT sense
    1121-1140 1711 GCCGAGAAGUAGCUCAGCA 1712 GCCGAGAAGuAGCUcAGcAdTsdT antis
    1268-1287 1713 CAAAGCUCACCCUUGGACA 1714 cAAAGcucAcccuuGGAcAdTsdT sense
    1268-1287 1715 UGUCCAAGGGUGAGCUUUG 1716 UGUCcAAGGGUGAGCUUUGdTsdT antis
    1290-1309 1717 GUGUUCAAAUCUUCAAAGA 1718 GuGuucAAAucuucAAAGAdTsdT sense
    1290-1309 1719 UCUUUGAAGAUUUGAACAC 1720 UCUUUGAAGAUUUGAAcACdTsdT antis
    1308-1327 1721 ACACCACCUGAGGCCAUUG 1722 AcAccAccuGAGGccAuuGdTsdT sense
    1308-1327 1723 CAAUGGCCUCAGGUGGUGU 1724 cAAUGGCCUcAGGUGGUGUdTsdT antis
    1312-1331 1725 CACCUGAGGCCAUUGCACU 1726 cAccuGAGGccAuuGcAcudTsdT sense
    1312-1331 1727 AGUGCAAUGGCCUCAGGUG 1728 AGUGcAAUGGCCUcAGGUGdTsdT antis
    1326-1345 1729 GCACUCUGCUCUAGCCUAC 1730 GcAcucuGcucuAGccuAcdTsdT sense
    1326-1345 1731 GUAGGCUAGAGCAGAGUGC 1732 GuAGGCuAGAGcAGAGUGCdTsdT antis
    1332-1351 1733 UGCUCUAGCCUACUGGAGU 1734 uGcucuAGccuAcuGGAGudTsdT sense
    1332-1351 1735 ACUCCAGUAGGCUAGAGCA 1736 ACUCcAGuAGGCuAGAGcAdTsdT antis
    1406-1425 1737 UGAACUGCGGAGACUCGGA 1738 uGAAcuGcGGAGAcucGGAdTsdT sense
    1406-1425 1739 UCCGAGUCUCCGCAGUUCA 1740 UCCGAGUCUCCGcAGUUcAdTsdT antis
    1407-1426 1741 GAACUGCGGAGACUCGGAG 1742 GAAcuGcGGAGAcucGGAGdTsdT sense
    1407-1426 1743 CUCCGAGUCUCCGCAGUUC 1744 CUCCGAGUCUCCGcAGUUCdTsdT antis
    1415-1434 1745 GAGACUCGGAGCCCAGCUC 1746 GAGAcucGGAGcccAGcucdTsdT sense
    1415-1434 1747 GAGCUGGGCUCCGAGUCUC 1748 GAGCUGGGCUCCGAGUCUCdTsdT antis
    1464-1483 1749 AACUUCAGUCCUGGUGAAC 1750 AAcuucAGuccuGGuGAAcdTsdT sense
    1464-1483 1751 GUUCACCAGGACUGAAGUU 1752 GUUcACcAGGACUGAAGUUdTsdT antis
    1465-1484 1753 ACUUCAGUCCUGGUGAACU 1754 AcuucAGuccuGGuGAAcudTsdT sense
    1465-1484 1755 AGUUCACCAGGACUGAAGU 1756 AGUUcACcAGGACUGAAGUdTsdT antis
    1479-1498 1757 GAACUGUCCAUCCAACCAU 1758 GAAcuGuccAuccAAccAudTsdT sense
    1479-1498 1759 AUGGUUGGAUGGACAGUUC 1760 AUGGUUGGAUGGAcAGUUCdTsdT antis
    1566-1585 1761 UCCUACAACCCAUCCUCAC 1762 uccuAcAAcccAuccucAcdTsdT sense
    1566-1585 1763 GUGAGGAUGGGUUGUAGGA 1764 GUGAGGAUGGGUUGuAGGAdTsdT antis
    1571-1590 1765 CAACCCAUCCUCACAAGCU 1766 cAAcccAuccucAcAAGcudTsdT sense
    1571-1590 1767 AGCUUGUGAGGAUGGGUUG 1768 AGCUUGUGAGGAUGGGUUGdTsdT antis
    1584-1603 1769 CAAGCUUUAACUGAAGCUC 1770 cAAGcuuuAAcuGAAGcucdTsdT sense
    1584-1603 1771 GAGCUUCAGUUAAAGCUUG 1772 GAGCUUcAGUuAAAGCUUGdTsdT antis
    1802-1821 1773 CUAGGCCUCCCUCAGCAGC 1774 cuAGGccucccucAGcAGcdTsdT sense
    1802-1821 1775 GCUGCUGAGGGAGGCCUAG 1776 GCUGCUGAGGGAGGCCuAGdTsdT antis
    1938-1957 1777 CCCCAGGCUACCACUCCUU 1778 ccccAGGcuAccAcuccuudTsdT sense
    1938-1957 1779 AAGGAGUGGUAGCCUGGGG 1780 AAGGAGUGGuAGCCUGGGGdTsdT antis
    1986-2005 1781 AAUAGAACCAGCCCAGCCC 1782 AAuAGAAccAGcccAGcccdTsdT sense
    1986-2005 1783 GGGCUGGGCUGGUUCUAUU 1784 GGGCUGGGCUGGUUCuAUUdTsdT antis
    1987-2006 1785 AUAGAACCAGCCCAGCCCA 1786 AuAGAAccAGcccAGcccAdTsdT sense
    1987-2006 1787 UGGGCUGGGCUGGUUCUAU 1788 UGGGCUGGGCUGGUUCuAUdTsdT antis
    2032-2051 1789 CUGGGUGUAAAUAGAUUGU 1790 cuGGGuGuAAAuAGAuuGudTsdT sense
    2032-2051 1791 ACAAUCUAUUUACACCCAG 1792 AcAAUCuAUUuAcACCcAGdTsdT antis
    2085-2104 1793 CCAUUCAACUUGCCCCCCC 1794 ccAuucAAcuuGcccccccdTsdT sense
    2085-2104 1795 GGGGGGGCAAGUUGAAUGG 1796 GGGGGGGcAAGUUGAAUGGdTsdT antis
    2090-2109 1797 CAACUUGCCCCCCCCAGCU 1798 cAAcuuGccccccccAGcudTsdT sense
    2090-2109 1799 AGCUGGGGGGGGCAAGUUG 1800 AGCUGGGGGGGGcAAGUUGdTsdT antis
    2094-2113 1801 UUGCCCCCCCCAGCUGUAC 1802 uuGccccccccAGcuGuAcdTsdT sense
    2094-2113 1803 GUACAGCUGGGGGGGGCAA 1804 GuAcAGCUGGGGGGGGcAAdTsdT antis
    2101-2120 1805 CCCCAGCUGUACCCCUUCU 1806 ccccAGcuGuAccccuucudTsdT sense
    2101-2120 1807 AGAAGGGGUACAGCUGGGG 1808 AGAAGGGGuAcAGCUGGGGdTsdT antis
    2104-2123 1809 CAGCUGUACCCCUUCUUGU 1810 cAGcuGuAccccuucuuGudTsdT sense
    2104-2123 1811 ACAAGAAGGGGUACAGCUG 1812 AcAAGAAGGGGuAcAGCUGdTsdT antis
    2105-2124 1813 AGCUGUACCCCUUCUUGUC 1814 AGcuGuAccccuucuuGucdTsdT sense
    2105-2124 1815 GACAAGAAGGGGUACAGCU 1816 GAcAAGAAGGGGuAcAGCUdTsdT antis
    2155-2174 1817 UCCUGGAAGGAGGGGAGUA 1818 uccuGGAAGGAGGGGAGuAdTsdT sense
    2155-2174 1819 UACUCCCCUCCUUCCAGGA 1820 uACUCCCCUCCUUCcAGGAdTsdT antis
    2167-2186 1821 GGGAGUAGAGAGAGUCCCU 1822 GGGAGuAGAGAGAGucccudTsdT sense
    2167-2186 1823 AGGGACUCUCUCUACUCCC 1824 AGGGACUCUCUCuACUCCCdTsdT antis
    2174-2193 1825 GAGAGAGUCCCUGGUGUCU 1826 GAGAGAGucccuGGuGucudTsdT sense
    2174-2193 1827 AGACACCAGGGACUCUCUC 1828 AGAcACcAGGGACUCUCUCdTsdT antis
    2216-2235 1829 UGUGUACAGACCUCUGUUC 1830 uGuGuAcAGAccucuGuucdTsdT sense
    2216-2235 1831 GAACAGAGGUCUGUACACA 1832 GAAcAGAGGUCUGuAcAcAdTsdT antis
    2217-2236 1833 GUGUACAGACCUCUGUUCA 1834 GuGuAcAGAccucuGuucAdTsdT sense
    2217-2236 1835 UGAACAGAGGUCUGUACAC 1836 UGAAcAGAGGUCUGuAcACdTsdT antis
    2236-2255 1837 AUAAAUUAUUGGCAUGAAA 1838 AuAAAuuAuuGGcAuGAAAdTsdT sense
    2236-2255 1839 UUUCAUGCCAAUAAUUUAU 1840 UUUcAUGCcAAuAAUUuAUdTsdT antis
    2237-2256 1841 UAAAUUAUUGGCAUGAAAC 1842 uAAAuuAuuGGcAuGAAAcdTsdT sense
    2237-2256 1843 GUUUCAUGCCAAUAAUUUA 1844 GUUUcAUGCcAAuAAUUuAdTsdT antis
    2245-2264 1845 UGGCAUGAAACCCUUAAAA 1846 uGGcAuGAAAcccuuAAAAdTsdT sense
    2245-2264 1847 UUUUAAGGGUUUCAUGCCA 1848 UUUuAAGGGUUUcAUGCcAdTsdT antis
    13-32 1849 AAGCCGACGGCAGAGGGAC 1850 AAGccGAcGGcAGAGGGAcdTsdT sense
    13-32 1851 GUCCCUCUGCCGUCGGCUU 1852 GUCCCUCUGCCGUCGGCUUdTsdT antis
    21-40 1853 GGCAGAGGGACUUCAUCUC 1854 GGcAGAGGGAcuucAucucdTsdT sense
    21-40 1855 GAGAUGAAGUCCCUCUGCC 1856 GAGAUGAAGUCCCUCUGCCdTsdT antis
    22-41 1857 GCAGAGGGACUUCAUCUCC 1858 GcAGAGGGAcuucAucuccdTsdT sense
    22-41 1859 GGAGAUGAAGUCCCUCUGC 1860 GGAGAUGAAGUCCCUCUGCdTsdT antis
    23-42 1861 CAGAGGGACUUCAUCUCCC 1862 cAGAGGGAcuucAucucccdTsdT sense
    23-42 1863 GGGAGAUGAAGUCCCUCUG 1864 GGGAGAUGAAGUCCCUCUGdTsdT antis
    25-44 1865 GAGGGACUUCAUCUCCCGG 1866 GAGGGAcuucAucucccGGdTsdT sense
    25-44 1867 CCGGGAGAUGAAGUCCCUC 1868 CCGGGAGAUGAAGUCCCUCdTsdT antis
    30-49 1869 ACUUCAUCUCCCGGCGUGC 1870 AcuucAucucccGGcGuGcdTsdT sense
    30-49 1871 GCACGCCGGGAGAUGAAGU 1872 GcACGCCGGGAGAUGAAGUdTsdT antis
    31-50 1873 CUUCAUCUCCCGGCGUGCC 1874 cuucAucucccGGcGuGccdTsdT sense
    31-50 1875 GGCACGCCGGGAGAUGAAG 1876 GGcACGCCGGGAGAUGAAGdTsdT antis
    32-51 1877 UUCAUCUCCCGGCGUGCCC 1878 uucAucucccGGcGuGcccdTsdT sense
    32-51 1879 GGGCACGCCGGGAGAUGAA 1880 GGGcACGCCGGGAGAUGAAdTsdT antis
    36-55 1881 UCUCCCGGCGUGCCCCGCG 1882 ucucccGGcGuGccccGcGdTsdT sense
    36-55 1883 CGCGGGGCACGCCGGGAGA 1884 CGCGGGGcACGCCGGGAGAdTsdT antis
    41-60 1885 CGGCGUGCCCCGCGGCGGG 1886 cGGcGuGccccGcGGcGGGdTsdT sense
    41-60 1887 CCCGCCGCGGGGCACGCCG 1888 CCCGCCGCGGGGcACGCCGdTsdT antis
    44-63 1889 CGUGCCCCGCGGCGGGCGC 1890 cGuGccccGcGGcGGGcGcdTsdT sense
    44-63 1891 GCGCCCGCCGCGGGGCACG 1892 GCGCCCGCCGCGGGGcACGdTsdT antis
    45-64 1893 GUGCCCCGCGGCGGGCGCU 1894 GuGccccGcGGcGGGcGcudTsdT sense
    45-64 1895 AGCGCCCGCCGCGGGGCAC 1896 AGCGCCCGCCGCGGGGcACdTsdT antis
    52-71 1897 GCGGCGGGCGCUGGGCCGG 1898 GcGGcGGGcGcuGGGccGGdTsdT sense
    52-71 1899 CCGGCCCAGCGCCCGCCGC 1900 CCGGCCcAGCGCCCGCCGCdTsdT antis
    58-77 1901 GGCGCUGGGCCGGAGCCGG 1902 GGcGcuGGGccGGAGccGGdTsdT sense
    58-77 1903 CCGGCUCCGGCCCAGCGCC 1904 CCGGCUCCGGCCcAGCGCCdTsdT antis
     84-103 1905 ACGGCGCGGCCUGGAAGAG 1906 AcGGcGcGGccuGGAAGAGdTsdT sense
     84-103 1907 CUCUUCCAGGCCGCGCCGU 1908 CUCUUCcAGGCCGCGCCGUdTsdT antis
     88-107 1909 CGCGGCCUGGAAGAGGCCG 1910 cGcGGccuGGAAGAGGccGdTsdT sense
     88-107 1911 CGGCCUCUUCCAGGCCGCG 1912 CGGCCUCUUCcAGGCCGCGdTsdT antis
     94-113 1913 CUGGAAGAGGCCGGAGCCC 1914 cuGGAAGAGGccGGAGcccdTsdT sense
     94-113 1915 GGGCUCCGGCCUCUUCCAG 1916 GGGCUCCGGCCUCUUCcAGdTsdT antis
     98-117 1917 AAGAGGCCGGAGCCCAGGG 1918 AAGAGGccGGAGcccAGGGdTsdT sense
     98-117 1919 CCCUGGGCUCCGGCCUCUU 1920 CCCUGGGCUCCGGCCUCUUdTsdT antis
    100-119 1921 GAGGCCGGAGCCCAGGGGA 1922 GAGGccGGAGcccAGGGGAdTsdT sense
    100-119 1923 UCCCCUGGGCUCCGGCCUC 1924 UCCCCUGGGCUCCGGCCUCdTsdT antis
    144-163 1925 GCAGCCCAGGCAGCCCGAG 1926 GcAGcccAGGcAGcccGAGdTsdT sense
    144-163 1927 CUCGGGCUGCCUGGGCUGC 1928 CUCGGGCUGCCUGGGCUGCdTsdT antis
    145-164 1929 CAGCCCAGGCAGCCCGAGC 1930 cAGcccAGGcAGcccGAGcdTsdT sense
    145-164 1931 GCUCGGGCUGCCUGGGCUG 1932 GCUCGGGCUGCCUGGGCUGdTsdT antis
    148-167 1933 CCCAGGCAGCCCGAGCCCC 1934 cccAGGcAGcccGAGccccdTsdT sense
    148-167 1935 GGGGCUCGGGCUGCCUGGG 1936 GGGGCUCGGGCUGCCUGGGdTsdT antis
    149-168 1937 CCAGGCAGCCCGAGCCCCG 1938 ccAGGcAGcccGAGccccGdTsdT sense
    149-168 1939 CGGGGCUCGGGCUGCCUGG 1940 CGGGGCUCGGGCUGCCUGGdTsdT antis
    157-176 1941 CCCGAGCCCCGCGGCCUGG 1942 cccGAGccccGcGGccuGGdTsdT sense
    157-176 1943 CCAGGCCGCGGGGCUCGGG 1944 CcAGGCCGCGGGGCUCGGGdTsdT antis
    168-187 1945 CGGCCUGGGCCUGCGCUCG 1946 cGGccuGGGccuGcGcucGdTsdT sense
    168-187 1947 CGAGCGCAGGCCCAGGCCG 1948 CGAGCGcAGGCCcAGGCCGdTsdT antis
    169-188 1949 GGCCUGGGCCUGCGCUCGG 1950 GGccuGGGccuGcGcucGGdTsdT sense
    169-188 1951 CCGAGCGCAGGCCCAGGCC 1952 CCGAGCGcAGGCCcAGGCCdTsdT antis
    175-194 1953 GGCCUGCGCUCGGCGCCAU 1954 GGccuGcGcucGGcGccAudTsdT sense
    175-194 1955 AUGGCGCCGAGCGCAGGCC 1956 AUGGCGCCGAGCGcAGGCCdTsdT antis
    179-198 1957 UGCGCUCGGCGCCAUGAGC 1958 uGcGcucGGcGccAuGAGcdTsdT sense
    179-198 1959 GCUCAUGGCGCCGAGCGCA 1960 GCUcAUGGCGCCGAGCGcAdTsdT antis
    192-211 1961 AUGAGCGGCGGCGGGCCUU 1962 AuGAGcGGcGGcGGGccuudTsdT sense
    192-211 1963 AAGGCCCGCCGCCGCUCAU 1964 AAGGCCCGCCGCCGCUcAUdTsdT antis
    193-212 1965 UGAGCGGCGGCGGGCCUUC 1966 uGAGcGGcGGcGGGccuucdTsdT sense
    193-212 1967 GAAGGCCCGCCGCCGCUCA 1968 GAAGGCCCGCCGCCGCUcAdTsdT antis
    194-213 1969 GAGCGGCGGCGGGCCUUCG 1970 GAGcGGcGGcGGGccuucGdTsdT sense
    194-213 1971 CGAAGGCCCGCCGCCGCUC 1972 CGAAGGCCCGCCGCCGCUCdTsdT antis
    195-214 1973 AGCGGCGGCGGGCCUUCGG 1974 AGcGGcGGcGGGccuucGGdTsdT sense
    195-214 1975 CCGAAGGCCCGCCGCCGCU 1976 CCGAAGGCCCGCCGCCGCUdTsdT antis
    197-216 1977 CGGCGGCGGGCCUUCGGGA 1978 cGGcGGcGGGccuucGGGAdTsdT sense
    197-216 1979 UCCCGAAGGCCCGCCGCCG 1980 UCCCGAAGGCCCGCCGCCGdTsdT antis
    200-219 1981 CGGCGGGCCUUCGGGAGGC 1982 cGGcGGGccuucGGGAGGcdTsdT sense
    200-219 1983 GCCUCCCGAAGGCCCGCCG 1984 GCCUCCCGAAGGCCCGCCGdTsdT antis
    246-265 1985 ACCAGCUCGUUCGCGGAGC 1986 AccAGcucGuucGcGGAGcdTsdT sense
    246-265 1987 GCUCCGCGAACGAGCUGGU 1988 GCUCCGCGAACGAGCUGGUdTsdT antis
    253-272 1989 CGUUCGCGGAGCCAGGAGG 1990 cGuucGcGGAGccAGGAGGdTsdT sense
    253-272 1991 CCUCCUGGCUCCGCGAACG 1992 CCUCCUGGCUCCGCGAACGdTsdT antis
    257-276 1993 CGCGGAGCCAGGAGGCGGA 1994 cGcGGAGccAGGAGGcGGAdTsdT sense
    257-276 1995 UCCGCCUCCUGGCUCCGCG 1996 UCCGCCUCCUGGCUCCGCGdTsdT antis
    258-277 1997 GCGGAGCCAGGAGGCGGAG 1998 GcGGAGccAGGAGGcGGAGdTsdT sense
    258-277 1999 CUCCGCCUCCUGGCUCCGC 2000 CUCCGCCUCCUGGCUCCGCdTsdT antis
    297-316 2001 CCCGGGGGCUCGGCCUCUG 2002 cccGGGGGcucGGccucuGdTsdT sense
    297-316 2003 CAGAGGCCGAGCCCCCGGG 2004 cAGAGGCCGAGCCCCCGGGdTsdT antis
    298-317 2005 CCGGGGGCUCGGCCUCUGG 2006 ccGGGGGcucGGccucuGGdTsdT sense
    298-317 2007 CCAGAGGCCGAGCCCCCGG 2008 CcAGAGGCCGAGCCCCCGGdTsdT antis
    321-340 2009 GGAGGCACUGGCGGCGGGA 2010 GGAGGcAcuGGcGGcGGGAdTsdT sense
    321-340 2011 UCCCGCCGCCAGUGCCUCC 2012 UCCCGCCGCcAGUGCCUCCdTsdT antis
    323-342 2013 AGGCACUGGCGGCGGGAAA 2014 AGGcAcuGGcGGcGGGAAAdTsdT sense
    323-342 2015 UUUCCCGCCGCCAGUGCCU 2016 UUUCCCGCCGCcAGUGCCUdTsdT antis
    325-344 2017 GCACUGGCGGCGGGAAAGC 2018 GcAcuGGcGGcGGGAAAGcdTsdT sense
    325-344 2019 GCUUUCCCGCCGCCAGUGC 2020 GCUUUCCCGCCGCcAGUGCdTsdT antis
    326-345 2021 CACUGGCGGCGGGAAAGCG 2022 cAcuGGcGGcGGGAAAGcGdTsdT sense
    326-345 2023 CGCUUUCCCGCCGCCAGUG 2024 CGCUUUCCCGCCGCcAGUGdTsdT antis
    338-357 2025 GAAAGCGUCAGUCGGGGCU 2026 GAAAGcGucAGucGGGGcudTsdT sense
    338-357 2027 AGCCCCGACUGACGCUUUC 2028 AGCCCCGACUGACGCUUUCdTsdT antis
    370-389 2029 UGGGAGCCUCGAGCUCCGG 2030 uGGGAGccucGAGcuccGGdTsdT sense
    370-389 2031 CCGGAGCUCGAGGCUCCCA 2032 CCGGAGCUCGAGGCUCCcAdTsdT antis
    371-390 2033 GGGAGCCUCGAGCUCCGGG 2034 GGGAGccucGAGcuccGGGdTsdT sense
    371-390 2035 CCCGGAGCUCGAGGCUCCC 2036 CCCGGAGCUCGAGGCUCCCdTsdT antis
    372-391 2037 GGAGCCUCGAGCUCCGGGG 2038 GGAGccucGAGcuccGGGGdTsdT sense
    372-391 2039 CCCCGGAGCUCGAGGCUCC 2040 CCCCGGAGCUCGAGGCUCCdTsdT antis
    373-392 2041 GAGCCUCGAGCUCCGGGGG 2042 GAGccucGAGcuccGGGGGdTsdT sense
    373-392 2043 CCCCCGGAGCUCGAGGCUC 2044 CCCCCGGAGCUCGAGGCUCdTsdT antis
    375-394 2045 GCCUCGAGCUCCGGGGGUG 2046 GccucGAGcuccGGGGGuGdTsdT sense
    375-394 2047 CACCCCCGGAGCUCGAGGC 2048 cACCCCCGGAGCUCGAGGCdTsdT antis
    380-399 2049 GAGCUCCGGGGGUGGCCCC 2050 GAGcuccGGGGGuGGccccdTsdT sense
    380-399 2051 GGGGCCACCCCCGGAGCUC 2052 GGGGCcACCCCCGGAGCUCdTsdT antis
    385-404 2053 CCGGGGGUGGCCCCAGCGG 2054 ccGGGGGuGGccccAGcGGdTsdT sense
    385-404 2055 CCGCUGGGGCCACCCCCGG 2056 CCGCUGGGGCcACCCCCGGdTsdT antis
    389-408 2057 GGGUGGCCCCAGCGGCAGC 2058 GGGuGGccccAGcGGcAGcdTsdT sense
    389-408 2059 GCUGCCGCUGGGGCCACCC 2060 GCUGCCGCUGGGGCcACCCdTsdT antis
    439-458 2061 GCACUAGCUUCCCGCCGCC 2062 GcAcuAGcuucccGccGccdTsdT sense
    439-458 2063 GGCGGCGGGAAGCUAGUGC 2064 GGCGGCGGGAAGCuAGUGCdTsdT antis
    440-459 2065 CACUAGCUUCCCGCCGCCG 2066 cAcuAGcuucccGccGccGdTsdT sense
    440-459 2067 CGGCGGCGGGAAGCUAGUG 2068 CGGCGGCGGGAAGCuAGUGdTsdT antis
    445-464 2069 GCUUCCCGCCGCCGGGAGU 2070 GcuucccGccGccGGGAGudTsdT sense
    445-464 2071 ACUCCCGGCGGCGGGAAGC 2072 ACUCCCGGCGGCGGGAAGCdTsdT antis
    447-466 2073 UUCCCGCCGCCGGGAGUGA 2074 uucccGccGccGGGAGuGAdTsdT sense
    447-466 2075 UCACUCCCGGCGGCGGGAA 2076 UcACUCCCGGCGGCGGGAAdTsdT antis
    463-482 2077 UGAAGCUGGGCCGUGACAG 2078 uGAAGcuGGGccGuGAcAGdTsdT sense
    463-482 2079 CUGUCACGGCCCAGCUUCA 2080 CUGUcACGGCCcAGCUUcAdTsdT antis
    471-490 2081 GGCCGUGACAGCGGGAAGG 2082 GGccGuGAcAGcGGGAAGGdTsdT sense
    471-490 2083 CCUUCCCGCUGUCACGGCC 2084 CCUUCCCGCUGUcACGGCCdTsdT antis
    474-493 2085 CGUGACAGCGGGAAGGUGA 2086 cGuGAcAGcGGGAAGGuGAdTsdT sense
    474-493 2087 UCACCUUCCCGCUGUCACG 2088 UcACCUUCCCGCUGUcACGdTsdT antis
    492-511 2089 ACCACAGUGGUAGCCACUG 2090 AccAcAGuGGuAGccAcuGdTsdT sense
    492-511 2091 CAGUGGCUACCACUGUGGU 2092 cAGUGGCuACcACUGUGGUdTsdT antis
    495-514 2093 ACAGUGGUAGCCACUGUAG 2094 AcAGuGGuAGccAcuGuAGdTsdT sense
    495-514 2095 CUACAGUGGCUACCACUGU 2096 CuAcAGUGGCuACcACUGUdTsdT antis
    496-515 2097 CAGUGGUAGCCACUGUAGG 2098 cAGuGGuAGccAcuGuAGGdTsdT sense
    496-515 2099 CCUACAGUGGCUACCACUG 2100 CCuAcAGUGGCuACcACUGdTsdT antis
    506-525 2101 CACUGUAGGCCAAGGCCCA 2102 cAcuGuAGGccAAGGcccAdTsdT sense
    506-525 2103 UGGGCCUUGGCCUACAGUG 2104 UGGGCCUUGGCCuAcAGUGdTsdT antis
    507-526 2105 ACUGUAGGCCAAGGCCCAG 2106 AcuGuAGGccAAGGcccAGdTsdT sense
    507-526 2107 CUGGGCCUUGGCCUACAGU 2108 CUGGGCCUUGGCCuAcAGUdTsdT antis
    509-528 2109 UGUAGGCCAAGGCCCAGAG 2110 uGuAGGccAAGGcccAGAGdTsdT sense
    509-528 2111 CUCUGGGCCUUGGCCUACA 2112 CUCUGGGCCUUGGCCuAcAdTsdT antis
    510-529 2113 GUAGGCCAAGGCCCAGAGC 2114 GuAGGccAAGGcccAGAGcdTsdT sense
    510-529 2115 GCUCUGGGCCUUGGCCUAC 2116 GCUCUGGGCCUUGGCCuACdTsdT antis
    582-601 2117 GGAGUAGUAUACCAGGCAC 2118 GGAGuAGuAuAccAGGcAcdTsdT sense
    582-601 2119 GUGCCUGGUAUACUACUCC 2120 GUGCCUGGuAuACuACUCCdTsdT antis
    585-604 2121 GUAGUAUACCAGGCACGGC 2122 GuAGuAuAccAGGcAcGGcdTsdT sense
    585-604 2123 GCCGUGCCUGGUAUACUAC 2124 GCCGUGCCUGGuAuACuACdTsdT antis
    595-614 2125 AGGCACGGCUGGCAGAGAC 2126 AGGcAcGGcuGGcAGAGAcdTsdT sense
    595-614 2127 GUCUCUGCCAGCCGUGCCU 2128 GUCUCUGCcAGCCGUGCCUdTsdT antis
    596-615 2129 GGCACGGCUGGCAGAGACG 2130 GGcAcGGcuGGcAGAGAcGdTsdT sense
    596-615 2131 CGUCUCUGCCAGCCGUGCC 2132 CGUCUCUGCcAGCCGUGCCdTsdT antis
    597-616 2133 GCACGGCUGGCAGAGACGA 2134 GcAcGGcuGGcAGAGAcGAdTsdT sense
    597-616 2135 UCGUCUCUGCCAGCCGUGC 2136 UCGUCUCUGCcAGCCGUGCdTsdT antis
    610-629 2137 AGACGAGGGAACUGGUGGC 2138 AGAcGAGGGAAcuGGuGGcdTsdT sense
    610-629 2139 GCCACCAGUUCCCUCGUCU 2140 GCcACcAGUUCCCUCGUCUdTsdT antis
    612-631 2141 ACGAGGGAACUGGUGGCCA 2142 AcGAGGGAAcuGGuGGccAdTsdT sense
    612-631 2143 UGGCCACCAGUUCCCUCGU 2144 UGGCcACcAGUUCCCUCGUdTsdT antis
    614-633 2145 GAGGGAACUGGUGGCCAUC 2146 GAGGGAAcuGGuGGccAucdTsdT sense
    614-633 2147 GAUGGCCACCAGUUCCCUC 2148 GAUGGCcACcAGUUCCCUCdTsdT antis
    646-665 2149 AGGACAAAAGGUUCAAGAA 2150 AGGAcAAAAGGuucAAGAAdTsdT sense
    646-665 2151 UUCUUGAACCUUUUGUCCU 2152 UUCUUGAACCUUUUGUCCUdTsdT antis
    661-680 2153 AGAACCGAGAACUGCAGAU 2154 AGAAccGAGAAcuGcAGAudTsdT sense
    661-680 2155 AUCUGCAGUUCUCGGUUCU 2156 AUCUGcAGUUCUCGGUUCUdTsdT antis
    668-687 2157 AGAACUGCAGAUUAUGCGU 2158 AGAAcuGcAGAuuAuGcGudTsdT sense
    668-687 2159 ACGCAUAAUCUGCAGUUCU 2160 ACGcAuAAUCUGcAGUUCUdTsdT antis
    669-688 2161 GAACUGCAGAUUAUGCGUA 2162 GAAcuGcAGAuuAuGcGuAdTsdT sense
    669-688 2163 UACGCAUAAUCUGCAGUUC 2164 uACGcAuAAUCUGcAGUUCdTsdT antis
    703-722 2165 AUAUUGUGAGGCUGCGGUA 2166 AuAuuGuGAGGcuGcGGuAdTsdT sense
    703-722 2167 UACCGCAGCCUCACAAUAU 2168 uACCGcAGCCUcAcAAuAUdTsdT antis
    704-723 2169 UAUUGUGAGGCUGCGGUAC 2170 uAuuGuGAGGcuGcGGuAcdTsdT sense
    704-723 2171 GUACCGCAGCCUCACAAUA 2172 GuACCGcAGCCUcAcAAuAdTsdT antis
    705-724 2173 AUUGUGAGGCUGCGGUACU 2174 AuuGuGAGGcuGcGGuAcudTsdT sense
    705-724 2175 AGUACCGCAGCCUCACAAU 2176 AGuACCGcAGCCUcAcAAUdTsdT antis
    738-757 2177 GGGGAGAAGAAGGACGAGC 2178 GGGGAGAAGAAGGAcGAGcdTsdT sense
    738-757 2179 GCUCGUCCUUCUUCUCCCC 2180 GCUCGUCCUUCUUCUCCCCdTsdT antis
    824-843 2181 GGCCAAGCUGAUCACCCCU 2182 GGccAAGcuGAucAccccudTsdT sense
    824-843 2183 AGGGGUGAUCAGCUUGGCC 2184 AGGGGUGAUcAGCUUGGCCdTsdT antis
    827-846 2185 CAAGCUGAUCACCCCUAUC 2186 cAAGcuGAucAccccuAucdTsdT sense
    827-846 2187 GAUAGGGGUGAUCAGCUUG 2188 GAuAGGGGUGAUcAGCUUGdTsdT antis
    879-898 2189 CGGAGCUUGGCCUACAUCC 2190 cGGAGcuuGGccuAcAuccdTsdT sense
    879-898 2191 GGAUGUAGGCCAAGCUCCG 2192 GGAUGuAGGCcAAGCUCCGdTsdT antis
    880-899 2193 GGAGCUUGGCCUACAUCCA 2194 GGAGcuuGGccuAcAuccAdTsdT sense
    880-899 2195 UGGAUGUAGGCCAAGCUCC 2196 UGGAUGuAGGCcAAGCUCCdTsdT antis
    881-900 2197 GAGCUUGGCCUACAUCCAC 2198 GAGcuuGGccuAcAuccAcdTsdT sense
    881-900 2199 GUGGAUGUAGGCCAAGCUC 2200 GUGGAUGuAGGCcAAGCUCdTsdT antis
    884-903 2201 CUUGGCCUACAUCCACUCC 2202 cuuGGccuAcAuccAcuccdTsdT sense
    884-903 2203 GGAGUGGAUGUAGGCCAAG 2204 GGAGUGGAUGuAGGCcAAGdTsdT antis
    886-905 2205 UGGCCUACAUCCACUCCCA 2206 uGGccuAcAuccAcucccAdTsdT sense
    886-905 2207 UGGGAGUGGAUGUAGGCCA 2208 UGGGAGUGGAUGuAGGCcAdTsdT antis
    896-915 2209 CCACUCCCAAGGUGUGUGU 2210 ccAcucccAAGGuGuGuGudTsdT sense
    896-915 2211 ACACACACCUUGGGAGUGG 2212 AcAcAcACCUUGGGAGUGGdTsdT antis
    916-935 2213 ACCGUGACAUCAAGCCCCA 2214 AccGuGAcAucAAGccccAdTsdT sense
    916-935 2215 UGGGGCUUGAUGUCACGGU 2216 UGGGGCUUGAUGUcACGGUdTsdT antis
    917-936 2217 CCGUGACAUCAAGCCCCAG 2218 ccGuGAcAucAAGccccAGdTsdT sense
    917-936 2219 CUGGGGCUUGAUGUCACGG 2220 CUGGGGCUUGAUGUcACGGdTsdT antis
    931-950 2221 CCCAGAAUUUGCUUGUGGA 2222 cccAGAAuuuGcuuGuGGAdTsdT sense
    931-950 2223 UCCACAAGCAAAUUCUGGG 2224 UCcAcAAGcAAAUUCUGGGdTsdT antis
    933-952 2225 CAGAAUUUGCUUGUGGACC 2226 cAGAAuuuGcuuGuGGAccdTsdT sense
    933-952 2227 GGUCCACAAGCAAAUUCUG 2228 GGUCcAcAAGcAAAUUCUGdTsdT antis
     991-1010 2229 CAAAGCAGCUGGUUCGGGG 2230 cAAAGcAGcuGGuucGGGGdTsdT sense
     991-1010 2231 CCCCGAACCAGCUGCUUUG 2232 CCCCGAACcAGCUGCUUUGdTsdT antis
     993-1012 2233 AAGCAGCUGGUUCGGGGGG 2234 AAGcAGcuGGuucGGGGGGdTsdT sense
     993-1012 2235 CCCCCCGAACCAGCUGCUU 2236 CCCCCCGAACcAGCUGCUUdTsdT antis
    1000-1019 2237 UGGUUCGGGGGGAGCCCAA 2238 uGGuucGGGGGGAGcccAAdTsdT sense
    1000-1019 2239 UUGGGCUCCCCCCGAACCA 2240 UUGGGCUCCCCCCGAACcAdTsdT antis
    1003-1022 2241 UUCGGGGGGAGCCCAAUGU 2242 uucGGGGGGAGcccAAuGudTsdT sense
    1003-1022 2243 ACAUUGGGCUCCCCCCGAA 2244 AcAUUGGGCUCCCCCCGAAdTsdT antis
    1004-1023 2245 UCGGGGGGAGCCCAAUGUG 2246 ucGGGGGGAGcccAAuGuGdTsdT sense
    1004-1023 2247 CACAUUGGGCUCCCCCCGA 2248 cAcAUUGGGCUCCCCCCGAdTsdT antis
    1006-1025 2249 GGGGGGAGCCCAAUGUGUC 2250 GGGGGGAGcccAAuGuGucdTsdT sense
    1006-1025 2251 GACACAUUGGGCUCCCCCC 2252 GAcAcAUUGGGCUCCCCCCdTsdT antis
    1015-1034 2253 CCAAUGUGUCCUACAUCUG 2254 ccAAuGuGuccuAcAucuGdTsdT sense
    1015-1034 2255 CAGAUGUAGGACACAUUGG 2256 cAGAUGuAGGAcAcAUUGGdTsdT antis
    1016-1035 2257 CAAUGUGUCCUACAUCUGC 2258 cAAuGuGuccuAcAucuGcdTsdT sense
    1016-1035 2259 GCAGAUGUAGGACACAUUG 2260 GcAGAUGuAGGAcAcAUUGdTsdT antis
    1031-1050 2261 CUGCUCUCGGUACUACCGU 2262 cuGcucucGGuAcuAccGudTsdT sense
    1031-1050 2263 ACGGUAGUACCGAGAGCAG 2264 ACGGuAGuACCGAGAGcAGdTsdT antis
    1045-1064 2265 ACCGUGCUCCAGAACUCAU 2266 AccGuGcuccAGAAcucAudTsdT sense
    1045-1064 2267 AUGAGUUCUGGAGCACGGU 2268 AUGAGUUCUGGAGcACGGUdTsdT antis
    1047-1066 2269 CGUGCUCCAGAACUCAUCU 2270 cGuGcuccAGAAcucAucudTsdT sense
    1047-1066 2271 AGAUGAGUUCUGGAGCACG 2272 AGAUGAGUUCUGGAGcACGdTsdT antis
    1051-1070 2273 CUCCAGAACUCAUCUUUGG 2274 cuccAGAAcucAucuuuGGdTsdT sense
    1051-1070 2275 CCAAAGAUGAGUUCUGGAG 2276 CcAAAGAUGAGUUCUGGAGdTsdT antis
    1055-1074 2277 AGAACUCAUCUUUGGAGCC 2278 AGAAcucAucuuuGGAGccdTsdT sense
    1055-1074 2279 GGCUCCAAAGAUGAGUUCU 2280 GGCUCcAAAGAUGAGUUCUdTsdT antis
    1058-1077 2281 ACUCAUCUUUGGAGCCACA 2282 AcucAucuuuGGAGccAcAdTsdT sense
    1058-1077 2283 UGUGGCUCCAAAGAUGAGU 2284 UGUGGCUCcAAAGAUGAGUdTsdT antis
    1061-1080 2285 CAUCUUUGGAGCCACAGAU 2286 cAucuuuGGAGccAcAGAudTsdT sense
    1061-1080 2287 AUCUGUGGCUCCAAAGAUG 2288 AUCUGUGGCUCcAAAGAUGdTsdT antis
    1062-1081 2289 AUCUUUGGAGCCACAGAUU 2290 AucuuuGGAGccAcAGAuudTsdT sense
    1062-1081 2291 AAUCUGUGGCUCCAAAGAU 2292 AAUCUGUGGCUCcAAAGAUdTsdT antis
    1086-1105 2293 UCGUCCAUCGAUGUGUGGU 2294 ucGuccAucGAuGuGuGGudTsdT sense
    1086-1105 2295 ACCACACAUCGAUGGACGA 2296 ACcAcAcAUCGAUGGACGAdTsdT antis
    1099-1118 2297 UGUGGUCGGCUGGCUGUGU 2298 uGuGGucGGcuGGcuGuGudTsdT sense
    1099-1118 2299 ACACAGCCAGCCGACCACA 2300 AcAcAGCcAGCCGACcAcAdTsdT antis
    1100-1119 2301 GUGGUCGGCUGGCUGUGUA 2302 GuGGucGGcuGGcuGuGuAdTsdT sense
    1100-1119 2303 UACACAGCCAGCCGACCAC 2304 uAcAcAGCcAGCCGACcACdTsdT antis
    1101-1120 2305 UGGUCGGCUGGCUGUGUAC 2306 uGGucGGcuGGcuGuGuAcdTsdT sense
    1101-1120 2307 GUACACAGCCAGCCGACCA 2308 GuAcAcAGCcAGCCGACcAdTsdT antis
    1112-1131 2309 CUGUGUACUUGCUGAGCUA 2310 cuGuGuAcuuGcuGAGcuAdTsdT sense
    1112-1131 2311 UAGCUCAGCAAGUACACAG 2312 uAGCUcAGcAAGuAcAcAGdTsdT antis
    1114-1133 2313 GUGUACUUGCUGAGCUACU 2314 GuGuAcuuGcuGAGcuAcudTsdT sense
    1114-1133 2315 AGUAGCUCAGCAAGUACAC 2316 AGuAGCUcAGcAAGuAcACdTsdT antis
    1115-1134 2317 UGUACUUGCUGAGCUACUU 2318 uGuAcuuGcuGAGcuAcuudTsdT sense
    1115-1134 2319 AAGUAGCUCAGCAAGUACA 2320 AAGuAGCUcAGcAAGuAcAdTsdT antis
    1119-1138 2321 CUUGCUGAGCUACUUCUCG 2322 cuuGcuGAGcuAcuucucGdTsdT sense
    1119-1138 2323 CGAGAAGUAGCUCAGCAAG 2324 CGAGAAGuAGCUcAGcAAGdTsdT antis
    1126-1145 2325 AGCUACUUCUCGGCCAGCC 2326 AGcuAcuucucGGccAGccdTsdT sense
    1126-1145 2327 GGCUGGCCGAGAAGUAGCU 2328 GGCUGGCCGAGAAGuAGCUdTsdT antis
    1139-1158 2329 CCAGCCCAUCUUCCCUGGG 2330 ccAGcccAucuucccuGGGdTsdT sense
    1139-1158 2331 CCCAGGGAAGAUGGGCUGG 2332 CCcAGGGAAGAUGGGCUGGdTsdT antis
    1146-1165 2333 AUCUUCCCUGGGGACAGUG 2334 AucuucccuGGGGAcAGuGdTsdT sense
    1146-1165 2335 CACUGUCCCCAGGGAAGAU 2336 cACUGUCCCcAGGGAAGAUdTsdT antis
    1224-1243 2337 CGAGAGAUGAACCCUAACU 2338 cGAGAGAuGAAcccuAAcudTsdT sense
    1224-1243 2339 AGUUAGGGUUCAUCUCUCG 2340 AGUuAGGGUUcAUCUCUCGdTsdT antis
    1263-1282 2341 CAGAUCAAAGCUCACCCUU 2342 cAGAucAAAGcucAcccuudTsdT sense
    1263-1282 2343 AAGGGUGAGCUUUGAUCUG 2344 AAGGGUGAGCUUUGAUCUGdTsdT antis
    1264-1283 2345 AGAUCAAAGCUCACCCUUG 2346 AGAucAAAGcucAcccuuGdTsdT sense
    1264-1283 2347 CAAGGGUGAGCUUUGAUCU 2348 cAAGGGUGAGCUUUGAUCUdTsdT antis
    1267-1286 2349 UCAAAGCUCACCCUUGGAC 2350 ucAAAGcucAcccuuGGAcdTsdT sense
    1267-1286 2351 GUCCAAGGGUGAGCUUUGA 2352 GUCcAAGGGUGAGCUUUGAdTsdT antis
    1285-1304 2353 CAAAGGUGUUCAAAUCUUC 2354 cAAAGGuGuucAAAucuucdTsdT sense
    1285-1304 2355 GAAGAUUUGAACACCUUUG 2356 GAAGAUUUGAAcACCUUUGdTsdT antis
    1286-1305 2357 AAAGGUGUUCAAAUCUUCA 2358 AAAGGuGuucAAAucuucAdTsdT sense
    1286-1305 2359 UGAAGAUUUGAACACCUUU 2360 UGAAGAUUUGAAcACCUUUdTsdT antis
    1295-1314 2361 CAAAUCUUCAAAGACACCA 2362 cAAAucuucAAAGAcAccAdTsdT sense
    1295-1314 2363 UGGUGUCUUUGAAGAUUUG 2364 UGGUGUCUUUGAAGAUUUGdTsdT antis
    1304-1323 2365 AAAGACACCACCUGAGGCC 2366 AAAGAcAccAccuGAGGccdTsdT sense
    1304-1323 2367 GGCCUCAGGUGGUGUCUUU 2368 GGCCUcAGGUGGUGUCUUUdTsdT antis
    1306-1325 2369 AGACACCACCUGAGGCCAU 2370 AGAcAccAccuGAGGccAudTsdT sense
    1306-1325 2371 AUGGCCUCAGGUGGUGUCU 2372 AUGGCCUcAGGUGGUGUCUdTsdT antis
    1307-1326 2373 GACACCACCUGAGGCCAUU 2374 GAcAccAccuGAGGccAuudTsdT sense
    1307-1326 2375 AAUGGCCUCAGGUGGUGUC 2376 AAUGGCCUcAGGUGGUGUCdTsdT antis
    1310-1329 2377 ACCACCUGAGGCCAUUGCA 2378 AccAccuGAGGccAuuGcAdTsdT sense
    1310-1329 2379 UGCAAUGGCCUCAGGUGGU 2380 UGcAAUGGCCUcAGGUGGUdTsdT antis
    1313-1332 2381 ACCUGAGGCCAUUGCACUC 2382 AccuGAGGccAuuGcAcucdTsdT sense
    1313-1332 2383 GAGUGCAAUGGCCUCAGGU 2384 GAGUGcAAUGGCCUcAGGUdTsdT antis
    1315-1334 2385 CUGAGGCCAUUGCACUCUG 2386 cuGAGGccAuuGcAcucuGdTsdT sense
    1315-1334 2387 CAGAGUGCAAUGGCCUCAG 2388 cAGAGUGcAAUGGCCUcAGdTsdT antis
    1322-1341 2389 CAUUGCACUCUGCUCUAGC 2390 cAuuGcAcucuGcucuAGcdTsdT sense
    1322-1341 2391 GCUAGAGCAGAGUGCAAUG 2392 GCuAGAGcAGAGUGcAAUGdTsdT antis
    1330-1349 2393 UCUGCUCUAGCCUACUGGA 2394 ucuGcucuAGccuAcuGGAdTsdT sense
    1330-1349 2395 UCCAGUAGGCUAGAGCAGA 2396 UCcAGuAGGCuAGAGcAGAdTsdT antis
    1344-1363 2397 CUGGAGUACACGCCAUCCU 2398 cuGGAGuAcAcGccAuccudTsdT sense
    1344-1363 2399 AGGAUGGCGUGUACUCCAG 2400 AGGAUGGCGUGuACUCcAGdTsdT antis
    1347-1366 2401 GAGUACACGCCAUCCUCAA 2402 GAGuAcAcGccAuccucAAdTsdT sense
    1347-1366 2403 UUGAGGAUGGCGUGUACUC 2404 UUGAGGAUGGCGUGuACUCdTsdT antis
    1350-1369 2405 UACACGCCAUCCUCAAGGC 2406 uAcAcGccAuccucAAGGcdTsdT sense
    1350-1369 2407 GCCUUGAGGAUGGCGUGUA 2408 GCCUUGAGGAUGGCGUGuAdTsdT antis
    1366-1385 2409 GGCUCUCCCCACUCGAGGC 2410 GGcucuccccAcucGAGGcdTsdT sense
    1366-1385 2411 GCCUCGAGUGGGGAGAGCC 2412 GCCUCGAGUGGGGAGAGCCdTsdT antis
    1367-1386 2413 GCUCUCCCCACUCGAGGCU 2414 GcucuccccAcucGAGGcudTsdT sense
    1367-1386 2415 AGCCUCGAGUGGGGAGAGC 2416 AGCCUCGAGUGGGGAGAGCdTsdT antis
    1368-1387 2417 CUCUCCCCACUCGAGGCUU 2418 cucuccccAcucGAGGcuudTsdT sense
    1368-1387 2419 AAGCCUCGAGUGGGGAGAG 2420 AAGCCUCGAGUGGGGAGAGdTsdT antis
    1403-1422 2421 CGAUGAACUGCGGAGACUC 2422 cGAuGAAcuGcGGAGAcucdTsdT sense
    1403-1422 2423 GAGUCUCCGCAGUUCAUCG 2424 GAGUCUCCGcAGUUcAUCGdTsdT antis
    1412-1431 2425 GCGGAGACUCGGAGCCCAG 2426 GcGGAGAcucGGAGcccAGdTsdT sense
    1412-1431 2427 CUGGGCUCCGAGUCUCCGC 2428 CUGGGCUCCGAGUCUCCGCdTsdT antis
    1413-1432 2429 CGGAGACUCGGAGCCCAGC 2430 cGGAGAcucGGAGcccAGcdTsdT sense
    1413-1432 2431 GCUGGGCUCCGAGUCUCCG 2432 GCUGGGCUCCGAGUCUCCGdTsdT antis
    1414-1433 2433 GGAGACUCGGAGCCCAGCU 2434 GGAGAcucGGAGcccAGcudTsdT sense
    1414-1433 2435 AGCUGGGCUCCGAGUCUCC 2436 AGCUGGGCUCCGAGUCUCCdTsdT antis
    1416-1435 2437 AGACUCGGAGCCCAGCUCC 2438 AGAcucGGAGcccAGcuccdTsdT sense
    1416-1435 2439 GGAGCUGGGCUCCGAGUCU 2440 GGAGCUGGGCUCCGAGUCUdTsdT antis
    1418-1437 2441 ACUCGGAGCCCAGCUCCCC 2442 AcucGGAGcccAGcuccccdTsdT sense
    1418-1437 2443 GGGGAGCUGGGCUCCGAGU 2444 GGGGAGCUGGGCUCCGAGUdTsdT antis
    1420-1439 2445 UCGGAGCCCAGCUCCCCAA 2446 ucGGAGcccAGcuccccAAdTsdT sense
    1420-1439 2447 UUGGGGAGCUGGGCUCCGA 2448 UUGGGGAGCUGGGCUCCGAdTsdT antis
    1438-1457 2449 ACGACCGCCCGCUUCCCCC 2450 AcGAccGcccGcuucccccdTsdT sense
    1438-1457 2451 GGGGGAAGCGGGCGGUCGU 2452 GGGGGAAGCGGGCGGUCGUdTsdT antis
    1447-1466 2453 CGCUUCCCCCCCUGUUCAA 2454 cGcuucccccccuGuucAAdTsdT sense
    1447-1466 2455 UUGAACAGGGGGGGAAGCG 2456 UUGAAcAGGGGGGGAAGCGdTsdT antis
    1471-1490 2457 GUCCUGGUGAACUGUCCAU 2458 GuccuGGuGAAcuGuccAudTsdT sense
    1471-1490 2459 AUGGACAGUUCACCAGGAC 2460 AUGGAcAGUUcACcAGGACdTsdT antis
    1476-1495 2461 GGUGAACUGUCCAUCCAAC 2462 GGuGAAcuGuccAuccAAcdTsdT sense
    1476-1495 2463 GUUGGAUGGACAGUUCACC 2464 GUUGGAUGGAcAGUUcACCdTsdT antis
    1477-1496 2465 GUGAACUGUCCAUCCAACC 2466 GuGAAcuGuccAuccAAccdTsdT sense
    1477-1496 2467 GGUUGGAUGGACAGUUCAC 2468 GGUUGGAUGGAcAGUUcACdTsdT antis
    1486-1505 2469 CCAUCCAACCAUCUCUCAA 2470 ccAuccAAccAucucucAAdTsdT sense
    1486-1505 2471 UUGAGAGAUGGUUGGAUGG 2472 UUGAGAGAUGGUUGGAUGGdTsdT antis
    1487-1506 2473 CAUCCAACCAUCUCUCAAU 2474 cAuccAAccAucucucAAudTsdT sense
    1487-1506 2475 AUUGAGAGAUGGUUGGAUG 2476 AUUGAGAGAUGGUUGGAUGdTsdT antis
    1491-1510 2477 CAACCAUCUCUCAAUGCCA 2478 cAAccAucucucAAuGccAdTsdT sense
    1491-1510 2479 UGGCAUUGAGAGAUGGUUG 2480 UGGcAUUGAGAGAUGGUUGdTsdT antis
    1492-1511 2481 AACCAUCUCUCAAUGCCAU 2482 AAccAucucucAAuGccAudTsdT sense
    1492-1511 2483 AUGGCAUUGAGAGAUGGUU 2484 AUGGcAUUGAGAGAUGGUUdTsdT antis
    1493-1512 2485 ACCAUCUCUCAAUGCCAUU 2486 AccAucucucAAuGccAuudTsdT sense
    1493-1512 2487 AAUGGCAUUGAGAGAUGGU 2488 AAUGGcAUUGAGAGAUGGUdTsdT antis
    1551-1570 2489 UCUCCCCUCACCACUUCCU 2490 ucuccccucAccAcuuccudTsdT sense
    1551-1570 2491 AGGAAGUGGUGAGGGGAGA 2492 AGGAAGUGGUGAGGGGAGAdTsdT antis
    1553-1572 2493 UCCCCUCACCACUUCCUAC 2494 uccccucAccAcuuccuAcdTsdT sense
    1553-1572 2495 GUAGGAAGUGGUGAGGGGA 2496 GuAGGAAGUGGUGAGGGGAdTsdT antis
    1556-1575 2497 CCUCACCACUUCCUACAAC 2498 ccucAccAcuuccuAcAAcdTsdT sense
    1556-1575 2499 GUUGUAGGAAGUGGUGAGG 2500 GUUGuAGGAAGUGGUGAGGdTsdT antis
    1560-1579 2501 ACCACUUCCUACAACCCAU 2502 AccAcuuccuAcAAcccAudTsdT sense
    1560-1579 2503 AUGGGUUGUAGGAAGUGGU 2504 AUGGGUUGuAGGAAGUGGUdTsdT antis
    1561-1580 2505 CCACUUCCUACAACCCAUC 2506 ccAcuuccuAcAAcccAucdTsdT sense
    1561-1580 2507 GAUGGGUUGUAGGAAGUGG 2508 GAUGGGUUGuAGGAAGUGGdTsdT antis
    1562-1581 2509 CACUUCCUACAACCCAUCC 2510 cAcuuccuAcAAcccAuccdTsdT sense
    1562-1581 2511 GGAUGGGUUGUAGGAAGUG 2512 GGAUGGGUUGuAGGAAGUGdTsdT antis
    1564-1583 2513 CUUCCUACAACCCAUCCUC 2514 cuuccuAcAAcccAuccucdTsdT sense
    1564-1583 2515 GAGGAUGGGUUGUAGGAAG 2516 GAGGAUGGGUUGuAGGAAGdTsdT antis
    1565-1584 2517 UUCCUACAACCCAUCCUCA 2518 uuccuAcAAcccAuccucAdTsdT sense
    1565-1584 2519 UGAGGAUGGGUUGUAGGAA 2520 UGAGGAUGGGUUGuAGGAAdTsdT antis
    1568-1587 2521 CUACAACCCAUCCUCACAA 2522 cuAcAAcccAuccucAcAAdTsdT sense
    1568-1587 2523 UUGUGAGGAUGGGUUGUAG 2524 UUGUGAGGAUGGGUUGuAGdTsdT antis
    1569-1588 2525 UACAACCCAUCCUCACAAG 2526 uAcAAcccAuccucAcAAGdTsdT sense
    1569-1588 2527 CUUGUGAGGAUGGGUUGUA 2528 CUUGUGAGGAUGGGUUGuAdTsdT antis
    1572-1591 2529 AACCCAUCCUCACAAGCUU 2530 AAcccAuccucAcAAGcuudTsdT sense
    1572-1591 2531 AAGCUUGUGAGGAUGGGUU 2532 AAGCUUGUGAGGAUGGGUUdTsdT antis
    1573-1592 2533 ACCCAUCCUCACAAGCUUU 2534 AcccAuccucAcAAGcuuudTsdT sense
    1573-1592 2535 AAAGCUUGUGAGGAUGGGU 2536 AAAGCUUGUGAGGAUGGGUdTsdT antis
    1590-1609 2537 UUAACUGAAGCUCAGACUG 2538 uuAAcuGAAGcucAGAcuGdTsdT sense
    1590-1609 2539 CAGUCUGAGCUUCAGUUAA 2540 cAGUCUGAGCUUcAGUuAAdTsdT antis
    1591-1610 2541 UAACUGAAGCUCAGACUGG 2542 uAAcuGAAGcucAGAcuGGdTsdT sense
    1591-1610 2543 CCAGUCUGAGCUUCAGUUA 2544 CcAGUCUGAGCUUcAGUuAdTsdT antis
    1592-1611 2545 AACUGAAGCUCAGACUGGC 2546 AAcuGAAGcucAGAcuGGcdTsdT sense
    1592-1611 2547 GCCAGUCUGAGCUUCAGUU 2548 GCcAGUCUGAGCUUcAGUUdTsdT antis
    1593-1612 2549 ACUGAAGCUCAGACUGGCC 2550 AcuGAAGcucAGAcuGGccdTsdT sense
    1593-1612 2551 GGCCAGUCUGAGCUUCAGU 2552 GGCcAGUCUGAGCUUcAGUdTsdT antis
    1595-1614 2553 UGAAGCUCAGACUGGCCAA 2554 uGAAGcucAGAcuGGccAAdTsdT sense
    1595-1614 2555 UUGGCCAGUCUGAGCUUCA 2556 UUGGCcAGUCUGAGCUUcAdTsdT antis
    1601-1620 2557 UCAGACUGGCCAAGAUUGG 2558 ucAGAcuGGccAAGAuuGGdTsdT sense
    1601-1620 2559 CCAAUCUUGGCCAGUCUGA 2560 CcAAUCUUGGCcAGUCUGAdTsdT antis
    1606-1625 2561 CUGGCCAAGAUUGGCAGCC 2562 cuGGccAAGAuuGGcAGccdTsdT sense
    1606-1625 2563 GGCUGCCAAUCUUGGCCAG 2564 GGCUGCcAAUCUUGGCcAGdTsdT antis
    1610-1629 2565 CCAAGAUUGGCAGCCAUCU 2566 ccAAGAuuGGcAGccAucudTsdT sense
    1610-1629 2567 AGAUGGCUGCCAAUCUUGG 2568 AGAUGGCUGCcAAUCUUGGdTsdT antis
    1614-1633 2569 GAUUGGCAGCCAUCUGAUG 2570 GAuuGGcAGccAucuGAuGdTsdT sense
    1614-1633 2571 CAUCAGAUGGCUGCCAAUC 2572 cAUcAGAUGGCUGCcAAUCdTsdT antis
    1650-1669 2573 GCUAGCUCUUCCUGAGGGC 2574 GcuAGcucuuccuGAGGGcdTsdT sense
    1650-1669 2575 GCCCUCAGGAAGAGCUAGC 2576 GCCCUcAGGAAGAGCuAGCdTsdT antis
    1654-1673 2577 GCUCUUCCUGAGGGCCCCA 2578 GcucuuccuGAGGGccccAdTsdT sense
    1654-1673 2579 UGGGGCCCUCAGGAAGAGC 2580 UGGGGCCCUcAGGAAGAGCdTsdT antis
    1657-1676 2581 CUUCCUGAGGGCCCCACCG 2582 cuuccuGAGGGccccAccGdTsdT sense
    1657-1676 2583 CGGUGGGGCCCUCAGGAAG 2584 CGGUGGGGCCCUcAGGAAGdTsdT antis
    1799-1818 2585 CAUCUAGGCCUCCCUCAGC 2586 cAucuAGGccucccucAGcdTsdT sense
    1799-1818 2587 GCUGAGGGAGGCCUAGAUG 2588 GCUGAGGGAGGCCuAGAUGdTsdT antis
    1801-1820 2589 UCUAGGCCUCCCUCAGCAG 2590 ucuAGGccucccucAGcAGdTsdT sense
    1801-1820 2591 CUGCUGAGGGAGGCCUAGA 2592 CUGCUGAGGGAGGCCuAGAdTsdT antis
    1839-1858 2593 UUUUUAAAGAGGAUUUUAA 2594 uuuuuAAAGAGGAuuuuAAdTsdT sense
    1839-1858 2595 UUAAAAUCCUCUUUAAAAA 2596 UuAAAAUCCUCUUuAAAAAdTsdT antis
    1840-1859 2597 UUUUAAAGAGGAUUUUAAC 2598 uuuuAAAGAGGAuuuuAAcdTsdT sense
    1840-1859 2599 GUUAAAAUCCUCUUUAAAA 2600 GUuAAAAUCCUCUUuAAAAdTsdT antis
    1841-1860 2601 UUUAAAGAGGAUUUUAACU 2602 uuuAAAGAGGAuuuuAAcudTsdT sense
    1841-1860 2603 AGUUAAAAUCCUCUUUAAA 2604 AGUuAAAAUCCUCUUuAAAdTsdT antis
    1842-1861 2605 UUAAAGAGGAUUUUAACUG 2606 uuAAAGAGGAuuuuAAcuGdTsdT sense
    1842-1861 2607 CAGUUAAAAUCCUCUUUAA 2608 cAGUuAAAAUCCUCUUuAAdTsdT antis
    1843-1862 2609 UAAAGAGGAUUUUAACUGU 2610 uAAAGAGGAuuuuAAcuGudTsdT sense
    1843-1862 2611 ACAGUUAAAAUCCUCUUUA 2612 AcAGUuAAAAUCCUCUUuAdTsdT antis
    1845-1864 2613 AAGAGGAUUUUAACUGUUU 2614 AAGAGGAuuuuAAcuGuuudTsdT sense
    1845-1864 2615 AAACAGUUAAAAUCCUCUU 2616 AAAcAGUuAAAAUCCUCUUdTsdT antis
    1849-1868 2617 GGAUUUUAACUGUUUGUAG 2618 GGAuuuuAAcuGuuuGuAGdTsdT sense
    1849-1868 2619 CUACAAACAGUUAAAAUCC 2620 CuAcAAAcAGUuAAAAUCCdTsdT antis
    1858-1877 2621 CUGUUUGUAGGGGAGGGGA 2622 cuGuuuGuAGGGGAGGGGAdTsdT sense
    1858-1877 2623 UCCCCUCCCCUACAAACAG 2624 UCCCCUCCCCuAcAAAcAGdTsdT antis
    1859-1878 2625 UGUUUGUAGGGGAGGGGAG 2626 uGuuuGuAGGGGAGGGGAGdTsdT sense
    1859-1878 2627 CUCCCCUCCCCUACAAACA 2628 CUCCCCUCCCCuAcAAAcAdTsdT antis
    1862-1881 2629 UUGUAGGGGAGGGGAGAAA 2630 uuGuAGGGGAGGGGAGAAAdTsdT sense
    1862-1881 2631 UUUCUCCCCUCCCCUACAA 2632 UUUCUCCCCUCCCCuAcAAdTsdT antis
    1863-1882 2633 UGUAGGGGAGGGGAGAAAA 2634 uGuAGGGGAGGGGAGAAAAdTsdT sense
    1863-1882 2635 UUUUCUCCCCUCCCCUACA 2636 UUUUCUCCCCUCCCCuAcAdTsdT antis
    1874-1893 2637 GGAGAAAAGGAAGGACGGG 2638 GGAGAAAAGGAAGGAcGGGdTsdT sense
    1874-1893 2639 CCCGUCCUUCCUUUUCUCC 2640 CCCGUCCUUCCUUUUCUCCdTsdT antis
    1875-1894 2641 GAGAAAAGGAAGGACGGGG 2642 GAGAAAAGGAAGGAcGGGGdTsdT sense
    1875-1894 2643 CCCCGUCCUUCCUUUUCUC 2644 CCCCGUCCUUCCUUUUCUCdTsdT antis
    1876-1895 2645 AGAAAAGGAAGGACGGGGU 2646 AGAAAAGGAAGGAcGGGGudTsdT sense
    1876-1895 2647 ACCCCGUCCUUCCUUUUCU 2648 ACCCCGUCCUUCCUUUUCUdTsdT antis
    1878-1897 2649 AAAAGGAAGGACGGGGUUU 2650 AAAAGGAAGGAcGGGGuuudTsdT sense
    1878-1897 2651 AAACCCCGUCCUUCCUUUU 2652 AAACCCCGUCCUUCCUUUUdTsdT antis
    1898-1917 2653 GGGGUGUGAGGACCUUCUA 2654 GGGGuGuGAGGAccuucuAdTsdT sense
    1898-1917 2655 UAGAAGGUCCUCACACCCC 2656 uAGAAGGUCCUcAcACCCCdTsdT antis
    1899-1918 2657 GGGUGUGAGGACCUUCUAC 2658 GGGuGuGAGGAccuucuAcdTsdT sense
    1899-1918 2659 GUAGAAGGUCCUCACACCC 2660 GuAGAAGGUCCUcAcACCCdTsdT antis
    1900-1919 2661 GGUGUGAGGACCUUCUACC 2662 GGuGuGAGGAccuucuAccdTsdT sense
    1900-1919 2663 GGUAGAAGGUCCUCACACC 2664 GGuAGAAGGUCCUcAcACCdTsdT antis
    1902-1921 2665 UGUGAGGACCUUCUACCCC 2666 uGuGAGGAccuucuAccccdTsdT sense
    1902-1921 2667 GGGGUAGAAGGUCCUCACA 2668 GGGGuAGAAGGUCCUcAcAdTsdT antis
    1903-1922 2669 GUGAGGACCUUCUACCCCC 2670 GuGAGGAccuucuAcccccdTsdT sense
    1903-1922 2671 GGGGGUAGAAGGUCCUCAC 2672 GGGGGuAGAAGGUCCUcACdTsdT antis
    1959-1978 2673 CUCCCCCCCUCUCCCAGGU 2674 cucccccccucucccAGGudTsdT sense
    1959-1978 2675 ACCUGGGAGAGGGGGGGAG 2676 ACCUGGGAGAGGGGGGGAGdTsdT antis
    1964-1983 2677 CCCCUCUCCCAGGUCCCUU 2678 ccccucucccAGGucccuudTsdT sense
    1964-1983 2679 AAGGGACCUGGGAGAGGGG 2680 AAGGGACCUGGGAGAGGGGdTsdT antis
    1970-1989 2681 UCCCAGGUCCCUUGUAAAU 2682 ucccAGGucccuuGuAAAudTsdT sense
    1970-1989 2683 AUUUACAAGGGACCUGGGA 2684 AUUuAcAAGGGACCUGGGAdTsdT antis
    1974-1993 2685 AGGUCCCUUGUAAAUAGAA 2686 AGGucccuuGuAAAuAGAAdTsdT sense
    1974-1993 2687 UUCUAUUUACAAGGGACCU 2688 UUCuAUUuAcAAGGGACCUdTsdT antis
    1983-2002 2689 GUAAAUAGAACCAGCCCAG 2690 GuAAAuAGAAccAGcccAGdTsdT sense
    1983-2002 2691 CUGGGCUGGUUCUAUUUAC 2692 CUGGGCUGGUUCuAUUuACdTsdT antis
    1984-2003 2693 UAAAUAGAACCAGCCCAGC 2694 uAAAuAGAAccAGcccAGcdTsdT sense
    1984-2003 2695 GCUGGGCUGGUUCUAUUUA 2696 GCUGGGCUGGUUCuAUUuAdTsdT antis
    1994-2013 2697 CAGCCCAGCCCAUCUCUCG 2698 cAGcccAGcccAucucucGdTsdT sense
    1994-2013 2699 CGAGAGAUGGGCUGGGCUG 2700 CGAGAGAUGGGCUGGGCUGdTsdT antis
    1995-2014 2701 AGCCCAGCCCAUCUCUCGU 2702 AGcccAGcccAucucucGudTsdT sense
    1995-2014 2703 ACGAGAGAUGGGCUGGGCU 2704 ACGAGAGAUGGGCUGGGCUdTsdT antis
    1996-2015 2705 GCCCAGCCCAUCUCUCGUC 2706 GcccAGcccAucucucGucdTsdT sense
    1996-2015 2707 GACGAGAGAUGGGCUGGGC 2708 GACGAGAGAUGGGCUGGGCdTsdT antis
    1998-2017 2709 CCAGCCCAUCUCUCGUCUU 2710 ccAGcccAucucucGucuudTsdT sense
    1998-2017 2711 AAGACGAGAGAUGGGCUGG 2712 AAGACGAGAGAUGGGCUGGdTsdT antis
    2016-2035 2713 UCCCUUCCCUGGCCCCCUG 2714 ucccuucccuGGcccccuGdTsdT sense
    2016-2035 2715 CAGGGGGCCAGGGAAGGGA 2716 cAGGGGGCcAGGGAAGGGAdTsdT antis
    2022-2041 2717 CCCUGGCCCCCUGGGUGUA 2718 cccuGGcccccuGGGuGuAdTsdT sense
    2022-2041 2719 UACACCCAGGGGGCCAGGG 2720 uAcACCcAGGGGGCcAGGGdTsdT antis
    2025-2044 2721 UGGCCCCCUGGGUGUAAAU 2722 uGGcccccuGGGuGuAAAudTsdT sense
    2025-2044 2723 AUUUACACCCAGGGGGCCA 2724 AUUuAcACCcAGGGGGCcAdTsdT antis
    2026-2045 2725 GGCCCCCUGGGUGUAAAUA 2726 GGcccccuGGGuGuAAAuAdTsdT sense
    2026-2045 2727 UAUUUACACCCAGGGGGCC 2728 uAUUuAcACCcAGGGGGCCdTsdT antis
    2035-2054 2729 GGUGUAAAUAGAUUGUUAU 2730 GGuGuAAAuAGAuuGuuAudTsdT sense
    2035-2054 2731 AUAACAAUCUAUUUACACC 2732 AuAAcAAUCuAUUuAcACCdTsdT antis
    2041-2060 2733 AAUAGAUUGUUAUAAUUUU 2734 AAuAGAuuGuuAuAAuuuudTsdT sense
    2041-2060 2735 AAAAUUAUAACAAUCUAUU 2736 AAAAUuAuAAcAAUCuAUUdTsdT antis
    2047-2066 2737 UUGUUAUAAUUUUUUCUUA 2738 uuGuuAuAAuuuuuucuuAdTsdT sense
    2047-2066 2739 UAAGAAAAAAUUAUAACAA 2740 uAAGAAAAAAUuAuAAcAAdTsdT antis
    2057-2076 2741 UUUUUCUUAAAGAAAACGU 2742 uuuuucuuAAAGAAAAcGudTsdT sense
    2057-2076 2743 ACGUUUUCUUUAAGAAAAA 2744 ACGUUUUCUUuAAGAAAAAdTsdT antis
    2058-2077 2745 UUUUCUUAAAGAAAACGUC 2746 uuuucuuAAAGAAAAcGucdTsdT sense
    2058-2077 2747 GACGUUUUCUUUAAGAAAA 2748 GACGUUUUCUUuAAGAAAAdTsdT antis
    2060-2079 2749 UUCUUAAAGAAAACGUCAA 2750 uucuuAAAGAAAAcGucAAdTsdT sense
    2060-2079 2751 UUGACGUUUUCUUUAAGAA 2752 UUGACGUUUUCUUuAAGAAdTsdT antis
    2066-2085 2753 AAGAAAACGUCAAUUCACA 2754 AAGAAAAcGucAAuucAcAdTsdT sense
    2066-2085 2755 UGUGAAUUGACGUUUUCUU 2756 UGUGAAUUGACGUUUUCUUdTsdT antis
    2075-2094 2757 UCAAUUCACACCAUUCAAC 2758 ucAAuucAcAccAuucAAcdTsdT sense
    2075-2094 2759 GUUGAAUGGUGUGAAUUGA 2760 GUUGAAUGGUGUGAAUUGAdTsdT antis
    2077-2096 2761 AAUUCACACCAUUCAACUU 2762 AAuucAcAccAuucAAcuudTsdT sense
    2077-2096 2763 AAGUUGAAUGGUGUGAAUU 2764 AAGUUGAAUGGUGUGAAUUdTsdT antis
    2079-2098 2765 UUCACACCAUUCAACUUGC 2766 uucAcAccAuucAAcuuGcdTsdT sense
    2079-2098 2767 GCAAGUUGAAUGGUGUGAA 2768 GcAAGUUGAAUGGUGUGAAdTsdT antis
    2081-2100 2769 CACACCAUUCAACUUGCCC 2770 cAcAccAuucAAcuuGcccdTsdT sense
    2081-2100 2771 GGGCAAGUUGAAUGGUGUG 2772 GGGcAAGUUGAAUGGUGUGdTsdT antis
    2091-2110 2773 AACUUGCCCCCCCCAGCUG 2774 AAcuuGccccccccAGcuGdTsdT sense
    2091-2110 2775 CAGCUGGGGGGGGCAAGUU 2776 cAGCUGGGGGGGGcAAGUUdTsdT antis
    2092-2111 2777 ACUUGCCCCCCCCAGCUGU 2778 AcuuGccccccccAGcuGudTsdT sense
    2092-2111 2779 ACAGCUGGGGGGGGCAAGU 2780 AcAGCUGGGGGGGGcAAGUdTsdT antis
    2096-2115 2781 GCCCCCCCCAGCUGUACCC 2782 GccccccccAGcuGuAcccdTsdT sense
    2096-2115 2783 GGGUACAGCUGGGGGGGGC 2784 GGGuAcAGCUGGGGGGGGCdTsdT antis
    2097-2116 2785 CCCCCCCCAGCUGUACCCC 2786 ccccccccAGcuGuAccccdTsdT sense
    2097-2116 2787 GGGGUACAGCUGGGGGGGG 2788 GGGGuAcAGCUGGGGGGGGdTsdT antis
    2098-2117 2789 CCCCCCCAGCUGUACCCCU 2790 cccccccAGcuGuAccccudTsdT sense
    2098-2117 2791 AGGGGUACAGCUGGGGGGG 2792 AGGGGuAcAGCUGGGGGGGdTsdT antis
    2099-2118 2793 CCCCCCAGCUGUACCCCUU 2794 ccccccAGcuGuAccccuudTsdT sense
    2099-2118 2795 AAGGGGUACAGCUGGGGGG 2796 AAGGGGuAcAGCUGGGGGGdTsdT antis
    2100-2119 2797 CCCCCAGCUGUACCCCUUC 2798 cccccAGcuGuAccccuucdTsdT sense
    2100-2119 2799 GAAGGGGUACAGCUGGGGG 2800 GAAGGGGuAcAGCUGGGGGdTsdT antis
    2107-2126 2801 CUGUACCCCUUCUUGUCCU 2802 cuGuAccccuucuuGuccudTsdT sense
    2107-2126 2803 AGGACAAGAAGGGGUACAG 2804 AGGAcAAGAAGGGGuAcAGdTsdT antis
    2108-2127 2805 UGUACCCCUUCUUGUCCUC 2806 uGuAccccuucuuGuccucdTsdT sense
    2108-2127 2807 GAGGACAAGAAGGGGUACA 2808 GAGGAcAAGAAGGGGuAcAdTsdT antis
    2123-2142 2809 CCUCUGCUCCCAAGGCUUC 2810 ccucuGcucccAAGGcuucdTsdT sense
    2123-2142 2811 GAAGCCUUGGGAGCAGAGG 2812 GAAGCCUUGGGAGcAGAGGdTsdT antis
    2124-2143 2813 CUCUGCUCCCAAGGCUUCC 2814 cucuGcucccAAGGcuuccdTsdT sense
    2124-2143 2815 GGAAGCCUUGGGAGCAGAG 2816 GGAAGCCUUGGGAGcAGAGdTsdT antis
    2151-2170 2817 CCCAUCCUGGAAGGAGGGG 2818 cccAuccuGGAAGGAGGGGdTsdT sense
    2151-2170 2819 CCCCUCCUUCCAGGAUGGG 2820 CCCCUCCUUCcAGGAUGGGdTsdT antis
    2157-2176 2821 CUGGAAGGAGGGGAGUAGA 2822 cuGGAAGGAGGGGAGuAGAdTsdT sense
    2157-2176 2823 UCUACUCCCCUCCUUCCAG 2824 UCuACUCCCCUCCUUCcAGdTsdT antis
    2158-2177 2825 UGGAAGGAGGGGAGUAGAG 2826 uGGAAGGAGGGGAGuAGAGdTsdT sense
    2158-2177 2827 CUCUACUCCCCUCCUUCCA 2828 CUCuACUCCCCUCCUUCcAdTsdT antis
    2159-2178 2829 GGAAGGAGGGGAGUAGAGA 2830 GGAAGGAGGGGAGuAGAGAdTsdT sense
    2159-2178 2831 UCUCUACUCCCCUCCUUCC 2832 UCUCuACUCCCCUCCUUCCdTsdT antis
    2160-2179 2833 GAAGGAGGGGAGUAGAGAG 2834 GAAGGAGGGGAGuAGAGAGdTsdT sense
    2160-2179 2835 CUCUCUACUCCCCUCCUUC 2836 CUCUCuACUCCCCUCCUUCdTsdT antis
    2165-2184 2837 AGGGGAGUAGAGAGAGUCC 2838 AGGGGAGuAGAGAGAGuccdTsdT sense
    2165-2184 2839 GGACUCUCUCUACUCCCCU 2840 GGACUCUCUCuACUCCCCUdTsdT antis
    2166-2185 2841 GGGGAGUAGAGAGAGUCCC 2842 GGGGAGuAGAGAGAGucccdTsdT sense
    2166-2185 2843 GGGACUCUCUCUACUCCCC 2844 GGGACUCUCUCuACUCCCCdTsdT antis
    2169-2188 2845 GAGUAGAGAGAGUCCCUGG 2846 GAGuAGAGAGAGucccuGGdTsdT sense
    2169-2188 2847 CCAGGGACUCUCUCUACUC 2848 CcAGGGACUCUCUCuACUCdTsdT antis
    2173-2192 2849 AGAGAGAGUCCCUGGUGUC 2850 AGAGAGAGucccuGGuGucdTsdT sense
    2173-2192 2851 GACACCAGGGACUCUCUCU 2852 GAcACcAGGGACUCUCUCUdTsdT antis
    2178-2197 2853 GAGUCCCUGGUGUCUUAGU 2854 GAGucccuGGuGucuuAGudTsdT sense
    2178-2197 2855 ACUAAGACACCAGGGACUC 2856 ACuAAGAcACcAGGGACUCdTsdT antis
    2179-2198 2857 AGUCCCUGGUGUCUUAGUU 2858 AGucccuGGuGucuuAGuudTsdT sense
    2179-2198 2859 AACUAAGACACCAGGGACU 2860 AACuAAGAcACcAGGGACUdTsdT antis
    2182-2201 2861 CCCUGGUGUCUUAGUUUCC 2862 cccuGGuGucuuAGuuuccdTsdT sense
    2182-2201 2863 GGAAACUAAGACACCAGGG 2864 GGAAACuAAGAcACcAGGGdTsdT antis
    2183-2202 2865 CCUGGUGUCUUAGUUUCCA 2866 ccuGGuGucuuAGuuuccAdTsdT sense
    2183-2202 2867 UGGAAACUAAGACACCAGG 2868 UGGAAACuAAGAcACcAGGdTsdT antis
    2188-2207 2869 UGUCUUAGUUUCCACAGUA 2870 uGucuuAGuuuccAcAGuAdTsdT sense
    2188-2207 2871 UACUGUGGAAACUAAGACA 2872 uACUGUGGAAACuAAGAcAdTsdT antis
    2198-2217 2873 UCCACAGUAAGGUUUGCCU 2874 uccAcAGuAAGGuuuGccudTsdT sense
    2198-2217 2875 AGGCAAACCUUACUGUGGA 2876 AGGcAAACCUuACUGUGGAdTsdT antis
    2199-2218 2877 CCACAGUAAGGUUUGCCUG 2878 ccAcAGuAAGGuuuGccuGdTsdT sense
    2199-2218 2879 CAGGCAAACCUUACUGUGG 2880 cAGGcAAACCUuACUGUGGdTsdT antis
    2200-2219 2881 CACAGUAAGGUUUGCCUGU 2882 cAcAGuAAGGuuuGccuGudTsdT sense
    2200-2219 2883 ACAGGCAAACCUUACUGUG 2884 AcAGGcAAACCUuACUGUGdTsdT antis
    2201-2220 2885 ACAGUAAGGUUUGCCUGUG 2886 AcAGuAAGGuuuGccuGuGdTsdT sense
    2201-2220 2887 CACAGGCAAACCUUACUGU 2888 cAcAGGcAAACCUuACUGUdTsdT antis
    2203-2222 2889 AGUAAGGUUUGCCUGUGUA 2890 AGuAAGGuuuGccuGuGuAdTsdT sense
    2203-2222 2891 UACACAGGCAAACCUUACU 2892 uAcAcAGGcAAACCUuACUdTsdT antis
    2204-2223 2893 GUAAGGUUUGCCUGUGUAC 2894 GuAAGGuuuGccuGuGuAcdTsdT sense
    2204-2223 2895 GUACACAGGCAAACCUUAC 2896 GuAcAcAGGcAAACCUuACdTsdT antis
    2205-2224 2897 UAAGGUUUGCCUGUGUACA 2898 uAAGGuuuGccuGuGuAcAdTsdT sense
    2205-2224 2899 UGUACACAGGCAAACCUUA 2900 UGuAcAcAGGcAAACCUuAdTsdT antis
    2210-2229 2901 UUUGCCUGUGUACAGACCU 2902 uuuGccuGuGuAcAGAccudTsdT sense
    2210-2229 2903 AGGUCUGUACACAGGCAAA 2904 AGGUCUGuAcAcAGGcAAAdTsdT antis
    2211-2230 2905 UUGCCUGUGUACAGACCUC 2906 uuGccuGuGuAcAGAccucdTsdT sense
    2211-2230 2907 GAGGUCUGUACACAGGCAA 2908 GAGGUCUGuAcAcAGGcAAdTsdT antis
    2214-2233 2909 CCUGUGUACAGACCUCUGU 2910 ccuGuGuAcAGAccucuGudTsdT sense
    2214-2233 2911 ACAGAGGUCUGUACACAGG 2912 AcAGAGGUCUGuAcAcAGGdTsdT antis
    2215-2234 2913 CUGUGUACAGACCUCUGUU 2914 cuGuGuAcAGAccucuGuudTsdT sense
    2215-2234 2915 AACAGAGGUCUGUACACAG 2916 AAcAGAGGUCUGuAcAcAGdTsdT antis
    2220-2239 2917 UACAGACCUCUGUUCAAUA 2918 uAcAGAccucuGuucAAuAdTsdT sense
    2220-2239 2919 UAUUGAACAGAGGUCUGUA 2920 uAUUGAAcAGAGGUCUGuAdTsdT antis
    2224-2243 2921 GACCUCUGUUCAAUAAAUU 2922 GAccucuGuucAAuAAAuudTsdT sense
    2224-2243 2923 AAUUUAUUGAACAGAGGUC 2924 AAUUuAUUGAAcAGAGGUCdTsdT antis
    2234-2253 2925 CAAUAAAUUAUUGGCAUGA 2926 cAAuAAAuuAuuGGcAuGAdTsdT sense
    2234-2253 2927 UCAUGCCAAUAAUUUAUUG 2928 UcAUGCcAAuAAUUuAUUGdTsdT antis
    51-70 2929 CGCGGCGGGCGCUGGGCCG 2930 cGcGGcGGGcGcuGGGccGdTsdT sense
    51-70 2931 CGGCCCAGCGCCCGCCGCG 2932 CGGCCcAGCGCCCGCCGCGdTsdT antis
    173-192 2933 UGGGCCUGCGCUCGGCGCC 2934 uGGGccuGcGcucGGcGccdTsdT sense
    173-192 2935 GGCGCCGAGCGCAGGCCCA 2936 GGCGCCGAGCGcAGGCCcAdTsdT antis
    205-224 2937 GGCCUUCGGGAGGCGGCCC 2938 GGccuucGGGAGGcGGcccdTsdT sense
    205-224 2939 GGGCCGCCUCCCGAAGGCC 2940 GGGCCGCCUCCCGAAGGCCdTsdT antis
    221-240 2941 CCCUGGGGGCUCGGGCCGG 2942 cccuGGGGGcucGGGccGGdTsdT sense
    221-240 2943 CCGGCCCGAGCCCCCAGGG 2944 CCGGCCCGAGCCCCcAGGGdTsdT antis
    224-243 2945 UGGGGGCUCGGGCCGGGCG 2946 uGGGGGcucGGGccGGGcGdTsdT sense
    224-243 2947 CGCCCGGCCCGAGCCCCCA 2948 CGCCCGGCCCGAGCCCCcAdTsdT antis
    387-406 2949 GGGGGUGGCCCCAGCGGCA 2950 GGGGGuGGccccAGcGGcAdTsdT sense
    387-406 2951 UGCCGCUGGGGCCACCCCC 2952 UGCCGCUGGGGCcACCCCCdTsdT antis
    392-411 2953 UGGCCCCAGCGGCAGCGGC 2954 uGGccccAGcGGcAGcGGcdTsdT sense
    392-411 2955 GCCGCUGCCGCUGGGGCCA 2956 GCCGCUGCCGCUGGGGCcAdTsdT antis
    465-484 2957 AAGCUGGGCCGUGACAGCG 2958 AAGcuGGGccGuGAcAGcGdTsdT sense
    465-484 2959 CGCUGUCACGGCCCAGCUU 2960 CGCUGUcACGGCCcAGCUUdTsdT antis
    505-524 2961 CCACUGUAGGCCAAGGCCC 2962 ccAcuGuAGGccAAGGcccdTsdT sense
    505-524 2963 GGGCCUUGGCCUACAGUGG 2964 GGGCCUUGGCCuAcAGUGGdTsdT antis
    587-606 2965 AGUAUACCAGGCACGGCUG 2966 AGuAuAccAGGcAcGGcuGdTsdT sense
    587-606 2967 CAGCCGUGCCUGGUAUACU 2968 cAGCCGUGCCUGGuAuACUdTsdT antis
    601-620 2969 GGCUGGCAGAGACGAGGGA 2970 GGcuGGcAGAGAcGAGGGAdTsdT sense
    601-620 2971 UCCCUCGUCUCUGCCAGCC 2972 UCCCUCGUCUCUGCcAGCCdTsdT antis
    743-762 2973 GAAGAAGGACGAGCUGUAU 2974 GAAGAAGGAcGAGcuGuAudTsdT sense
    743-762 2975 AUACAGCUCGUCCUUCUUC 2976 AuAcAGCUCGUCCUUCUUCdTsdT antis
    927-946 2977 AAGCCCCAGAAUUUGCUUG 2978 AAGccccAGAAuuuGcuuGdTsdT sense
    927-946 2979 CAAGCAAAUUCUGGGGCUU 2980 cAAGcAAAUUCUGGGGCUUdTsdT antis
    932-951 2981 CCAGAAUUUGCUUGUGGAC 2982 ccAGAAuuuGcuuGuGGAcdTsdT sense
    932-951 2983 GUCCACAAGCAAAUUCUGG 2984 GUCcAcAAGcAAAUUCUGGdTsdT antis
    1054-1073 2985 CAGAACUCAUCUUUGGAGC 2986 cAGAAcucAucuuuGGAGcdTsdT sense
    1054-1073 2987 GCUCCAAAGAUGAGUUCUG 2988 GCUCcAAAGAUGAGUUCUGdTsdT antis
    1060-1079 2989 UCAUCUUUGGAGCCACAGA 2990 ucAucuuuGGAGccAcAGAdTsdT sense
    1060-1079 2991 UCUGUGGCUCCAAAGAUGA 2992 UCUGUGGCUCcAAAGAUGAdTsdT antis
    1068-1087 2993 GGAGCCACAGAUUACACCU 2994 GGAGccAcAGAuuAcAccudTsdT sense
    1068-1087 2995 AGGUGUAAUCUGUGGCUCC 2996 AGGUGuAAUCUGUGGCUCCdTsdT antis
    1094-1113 2997 CGAUGUGUGGUCGGCUGGC 2998 cGAuGuGuGGucGGcuGGcdTsdT sense
    1094-1113 2999 GCCAGCCGACCACACAUCG 3000 GCcAGCCGACcAcAcAUCGdTsdT antis
    1107-1126 3001 GCUGGCUGUGUACUUGCUG 3002 GcuGGcuGuGuAcuuGcuGdTsdT sense
    1107-1126 3003 CAGCAAGUACACAGCCAGC 3004 cAGcAAGuAcAcAGCcAGCdTsdT antis
    1108-1127 3005 CUGGCUGUGUACUUGCUGA 3006 cuGGcuGuGuAcuuGcuGAdTsdT sense
    1108-1127 3007 UCAGCAAGUACACAGCCAG 3008 UcAGcAAGuAcAcAGCcAGdTsdT antis
    1138-1157 3009 GCCAGCCCAUCUUCCCUGG 3010 GccAGcccAucuucccuGGdTsdT sense
    1138-1157 3011 CCAGGGAAGAUGGGCUGGC 3012 CcAGGGAAGAUGGGCUGGCdTsdT antis
    1149-1168 3013 UUCCCUGGGGACAGUGGGG 3014 uucccuGGGGAcAGuGGGGdTsdT sense
    1149-1168 3015 CCCCACUGUCCCCAGGGAA 3016 CCCcACUGUCCCcAGGGAAdTsdT antis
    1474-1493 3017 CUGGUGAACUGUCCAUCCA 3018 cuGGuGAAcuGuccAuccAdTsdT sense
    1474-1493 3019 UGGAUGGACAGUUCACCAG 3020 UGGAUGGAcAGUUcACcAGdTsdT antis
    1480-1499 3021 AACUGUCCAUCCAACCAUC 3022 AAcuGuccAuccAAccAucdTsdT sense
    1480-1499 3023 GAUGGUUGGAUGGACAGUU 3024 GAUGGUUGGAUGGAcAGUUdTsdT antis
    1555-1574 3025 CCCUCACCACUUCCUACAA 3026 cccucAccAcuuccuAcAAdTsdT sense
    1555-1574 3027 UUGUAGGAAGUGGUGAGGG 3028 UUGuAGGAAGUGGUGAGGGdTsdT antis
    1848-1867 3029 AGGAUUUUAACUGUUUGUA 3030 AGGAuuuuAAcuGuuuGuAdTsdT sense
    1848-1867 3031 UACAAACAGUUAAAAUCCU 3032 uAcAAAcAGUuAAAAUCCUdTsdT antis
    2031-2050 3033 CCUGGGUGUAAAUAGAUUG 3034 ccuGGGuGuAAAuAGAuuGdTsdT sense
    2031-2050 3035 CAAUCUAUUUACACCCAGG 3036 cAAUCuAUUuAcACCcAGGdTsdT antis
    2042-2061 3037 AUAGAUUGUUAUAAUUUUU 3038 AuAGAuuGuuAuAAuuuuudTsdT sense
    2042-2061 3039 AAAAAUUAUAACAAUCUAU 3040 AAAAAUuAuAAcAAUCuAUdTsdT antis
    2127-2146 3041 UGCUCCCAAGGCUUCCUCC 3042 uGcucccAAGGcuuccuccdTsdT sense
    2127-2146 3043 GGAGGAAGCCUUGGGAGCA 3044 GGAGGAAGCCUUGGGAGcAdTsdT antis
    2230-2249 3045 UGUUCAAUAAAUUAUUGGC 3046 uGuucAAuAAAuuAuuGGcdTsdT sense
    2230-2249 3047 GCCAAUAAUUUAUUGAACA 3048 GCcAAuAAUUuAUUGAAcAdTsdT antis
    48-67 3049 CCCCGCGGCGGGCGCUGGG 3050 ccccGcGGcGGGcGcuGGGdTsdT sense
    48-67 3051 CCCAGCGCCCGCCGCGGGG 3052 CCcAGCGCCCGCCGCGGGGdTsdT antis
    50-69 3053 CCGCGGCGGGCGCUGGGCC 3054 ccGcGGcGGGcGcuGGGccdTsdT sense
    50-69 3055 GGCCCAGCGCCCGCCGCGG 3056 GGCCcAGCGCCCGCCGCGGdTsdT antis
    56-75 3057 CGGGCGCUGGGCCGGAGCC 3058 cGGGcGcuGGGccGGAGccdTsdT sense
    56-75 3059 GGCUCCGGCCCAGCGCCCG 3060 GGCUCCGGCCcAGCGCCCGdTsdT antis
     89-108 3061 GCGGCCUGGAAGAGGCCGG 3062 GcGGccuGGAAGAGGccGGdTsdT sense
     89-108 3063 CCGGCCUCUUCCAGGCCGC 3064 CCGGCCUCUUCcAGGCCGCdTsdT antis
     91-110 3065 GGCCUGGAAGAGGCCGGAG 3066 GGccuGGAAGAGGccGGAGdTsdT sense
     91-110 3067 CUCCGGCCUCUUCCAGGCC 3068 CUCCGGCCUCUUCcAGGCCdTsdT antis
     95-114 3069 UGGAAGAGGCCGGAGCCCA 3070 uGGAAGAGGccGGAGcccAdTsdT sense
     95-114 3071 UGGGCUCCGGCCUCUUCCA 3072 UGGGCUCCGGCCUCUUCcAdTsdT antis
     96-115 3073 GGAAGAGGCCGGAGCCCAG 3074 GGAAGAGGccGGAGcccAGdTsdT sense
     96-115 3075 CUGGGCUCCGGCCUCUUCC 3076 CUGGGCUCCGGCCUCUUCCdTsdT antis
    103-122 3077 GCCGGAGCCCAGGGGAGGC 3078 GccGGAGcccAGGGGAGGcdTsdT sense
    103-122 3079 GCCUCCCCUGGGCUCCGGC 3080 GCCUCCCCUGGGCUCCGGCdTsdT antis
    104-123 3081 CCGGAGCCCAGGGGAGGCG 3082 ccGGAGcccAGGGGAGGcGdTsdT sense
    104-123 3083 CGCCUCCCCUGGGCUCCGG 3084 CGCCUCCCCUGGGCUCCGGdTsdT antis
    105-124 3085 CGGAGCCCAGGGGAGGCGG 3086 cGGAGcccAGGGGAGGcGGdTsdT sense
    105-124 3087 CCGCCUCCCCUGGGCUCCG 3088 CCGCCUCCCCUGGGCUCCGdTsdT antis
    134-153 3089 AGCGGCGGGGGCAGCCCAG 3090 AGcGGcGGGGGcAGcccAGdTsdT sense
    134-153 3091 CUGGGCUGCCCCCGCCGCU 3092 CUGGGCUGCCCCCGCCGCUdTsdT antis
    147-166 3093 GCCCAGGCAGCCCGAGCCC 3094 GcccAGGcAGcccGAGcccdTsdT sense
    147-166 3095 GGGCUCGGGCUGCCUGGGC 3096 GGGCUCGGGCUGCCUGGGCdTsdT antis
    158-177 3097 CCGAGCCCCGCGGCCUGGG 3098 ccGAGccccGcGGccuGGGdTsdT sense
    158-177 3099 CCCAGGCCGCGGGGCUCGG 3100 CCcAGGCCGCGGGGCUCGGdTsdT antis
    167-186 3101 GCGGCCUGGGCCUGCGCUC 3102 GcGGccuGGGccuGcGcucdTsdT sense
    167-186 3103 GAGCGCAGGCCCAGGCCGC 3104 GAGCGcAGGCCcAGGCCGCdTsdT antis
    172-191 3105 CUGGGCCUGCGCUCGGCGC 3106 cuGGGccuGcGcucGGcGcdTsdT sense
    172-191 3107 GCGCCGAGCGCAGGCCCAG 3108 GCGCCGAGCGcAGGCCcAGdTsdT antis
    204-223 3109 GGGCCUUCGGGAGGCGGCC 3110 GGGccuucGGGAGGcGGccdTsdT sense
    204-223 3111 GGCCGCCUCCCGAAGGCCC 3112 GGCCGCCUCCCGAAGGCCCdTsdT antis
    209-228 3113 UUCGGGAGGCGGCCCUGGG 3114 uucGGGAGGcGGcccuGGGdTsdT sense
    209-228 3115 CCCAGGGCCGCCUCCCGAA 3116 CCcAGGGCCGCCUCCCGAAdTsdT antis
    231-250 3117 UCGGGCCGGGCGCGGACCA 3118 ucGGGccGGGcGcGGAccAdTsdT sense
    231-250 3119 UGGUCCGCGCCCGGCCCGA 3120 UGGUCCGCGCCCGGCCCGAdTsdT antis
    256-275 3121 UCGCGGAGCCAGGAGGCGG 3122 ucGcGGAGccAGGAGGcGGdTsdT sense
    256-275 3123 CCGCCUCCUGGCUCCGCGA 3124 CCGCCUCCUGGCUCCGCGAdTsdT antis
    294-313 3125 GGCCCCGGGGGCUCGGCCU 3126 GGccccGGGGGcucGGccudTsdT sense
    294-313 3127 AGGCCGAGCCCCCGGGGCC 3128 AGGCCGAGCCCCCGGGGCCdTsdT antis
    295-314 3129 GCCCCGGGGGCUCGGCCUC 3130 GccccGGGGGcucGGccucdTsdT sense
    295-314 3131 GAGGCCGAGCCCCCGGGGC 3132 GAGGCCGAGCCCCCGGGGCdTsdT antis
    318-337 3133 CCAGGAGGCACUGGCGGCG 3134 ccAGGAGGcAcuGGcGGcGdTsdT sense
    318-337 3135 CGCCGCCAGUGCCUCCUGG 3136 CGCCGCcAGUGCCUCCUGGdTsdT antis
    369-388 3137 GUGGGAGCCUCGAGCUCCG 3138 GuGGGAGccucGAGcuccGdTsdT sense
    369-388 3139 CGGAGCUCGAGGCUCCCAC 3140 CGGAGCUCGAGGCUCCcACdTsdT antis
    386-405 3141 CGGGGGUGGCCCCAGCGGC 3142 cGGGGGuGGccccAGcGGcdTsdT sense
    386-405 3143 GCCGCUGGGGCCACCCCCG 3144 GCCGCUGGGGCcACCCCCGdTsdT antis
    390-409 3145 GGUGGCCCCAGCGGCAGCG 3146 GGuGGccccAGcGGcAGcGdTsdT sense
    390-409 3147 CGCUGCCGCUGGGGCCACC 3148 CGCUGCCGCUGGGGCcACCdTsdT antis
    391-410 3149 GUGGCCCCAGCGGCAGCGG 3150 GuGGccccAGcGGcAGcGGdTsdT sense
    391-410 3151 CCGCUGCCGCUGGGGCCAC 3152 CCGCUGCCGCUGGGGCcACdTsdT antis
    460-479 3153 GAGUGAAGCUGGGCCGUGA 3154 GAGuGAAGcuGGGccGuGAdTsdT sense
    460-479 3155 UCACGGCCCAGCUUCACUC 3156 UcACGGCCcAGCUUcACUCdTsdT antis
    491-510 3157 GACCACAGUGGUAGCCACU 3158 GAccAcAGuGGuAGccAcudTsdT sense
    491-510 3159 AGUGGCUACCACUGUGGUC 3160 AGUGGCuACcACUGUGGUCdTsdT antis
    494-513 3161 CACAGUGGUAGCCACUGUA 3162 cAcAGuGGuAGccAcuGuAdTsdT sense
    494-513 3163 UACAGUGGCUACCACUGUG 3164 uAcAGUGGCuACcACUGUGdTsdT antis
    504-523 3165 GCCACUGUAGGCCAAGGCC 3166 GccAcuGuAGGccAAGGccdTsdT sense
    504-523 3167 GGCCUUGGCCUACAGUGGC 3168 GGCCUUGGCCuAcAGUGGCdTsdT antis
    593-612 3169 CCAGGCACGGCUGGCAGAG 3170 ccAGGcAcGGcuGGcAGAGdTsdT sense
    593-612 3171 CUCUGCCAGCCGUGCCUGG 3172 CUCUGCcAGCCGUGCCUGGdTsdT antis
    600-619 3173 CGGCUGGCAGAGACGAGGG 3174 cGGcuGGcAGAGAcGAGGGdTsdT sense
    600-619 3175 CCCUCGUCUCUGCCAGCCG 3176 CCCUCGUCUCUGCcAGCCGdTsdT antis
    613-632 3177 CGAGGGAACUGGUGGCCAU 3178 cGAGGGAAcuGGuGGccAudTsdT sense
    613-632 3179 AUGGCCACCAGUUCCCUCG 3180 AUGGCcACcAGUUCCCUCGdTsdT antis
    650-669 3181 CAAAAGGUUCAAGAACCGA 3182 cAAAAGGuucAAGAAccGAdTsdT sense
    650-669 3183 UCGGUUCUUGAACCUUUUG 3184 UCGGUUCUUGAACCUUUUGdTsdT antis
    841-860 3185 CUAUCAUCUACAUCAAGGU 3186 cuAucAucuAcAucAAGGudTsdT sense
    841-860 3187 ACCUUGAUGUAGAUGAUAG 3188 ACCUUGAUGuAGAUGAuAGdTsdT antis
    842-861 3189 UAUCAUCUACAUCAAGGUG 3190 uAucAucuAcAucAAGGuGdTsdT sense
    842-861 3191 CACCUUGAUGUAGAUGAUA 3192 cACCUUGAUGuAGAUGAuAdTsdT antis
    895-914 3193 UCCACUCCCAAGGUGUGUG 3194 uccAcucccAAGGuGuGuGdTsdT sense
    895-914 3195 CACACACCUUGGGAGUGGA 3196 cAcAcACCUUGGGAGUGGAdTsdT antis
    900-919 3197 UCCCAAGGUGUGUGUCACC 3198 ucccAAGGuGuGuGucAccdTsdT sense
    900-919 3199 GGUGACACACACCUUGGGA 3200 GGUGAcAcAcACCUUGGGAdTsdT antis
    901-920 3201 CCCAAGGUGUGUGUCACCG 3202 cccAAGGuGuGuGucAccGdTsdT sense
    901-920 3203 CGGUGACACACACCUUGGG 3204 CGGUGAcAcAcACCUUGGGdTsdT antis
    924-943 3205 AUCAAGCCCCAGAAUUUGC 3206 AucAAGccccAGAAuuuGcdTsdT sense
    924-943 3207 GCAAAUUCUGGGGCUUGAU 3208 GcAAAUUCUGGGGCUUGAUdTsdT antis
    925-944 3209 UCAAGCCCCAGAAUUUGCU 3210 ucAAGccccAGAAuuuGcudTsdT sense
    925-944 3211 AGCAAAUUCUGGGGCUUGA 3212 AGcAAAUUCUGGGGCUUGAdTsdT antis
    926-945 3213 CAAGCCCCAGAAUUUGCUU 3214 cAAGccccAGAAuuuGcuudTsdT sense
    926-945 3215 AAGCAAAUUCUGGGGCUUG 3216 AAGcAAAUUCUGGGGCUUGdTsdT antis
    953-972 3217 UGACACUGCUGUCCUCAAG 3218 uGAcAcuGcuGuccucAAGdTsdT sense
    953-972 3219 CUUGAGGACAGCAGUGUCA 3220 CUUGAGGAcAGcAGUGUcAdTsdT antis
    1053-1072 3221 CCAGAACUCAUCUUUGGAG 3222 ccAGAAcucAucuuuGGAGdTsdT sense
    1053-1072 3223 CUCCAAAGAUGAGUUCUGG 3224 CUCcAAAGAUGAGUUCUGGdTsdT antis
    1057-1076 3225 AACUCAUCUUUGGAGCCAC 3226 AAcucAucuuuGGAGccAcdTsdT sense
    1057-1076 3227 GUGGCUCCAAAGAUGAGUU 3228 GUGGCUCcAAAGAUGAGUUdTsdT antis
    1063-1082 3229 UCUUUGGAGCCACAGAUUA 3230 ucuuuGGAGccAcAGAuuAdTsdT sense
    1063-1082 3231 UAAUCUGUGGCUCCAAAGA 3232 uAAUCUGUGGCUCcAAAGAdTsdT antis
    1069-1088 3233 GAGCCACAGAUUACACCUC 3234 GAGccAcAGAuuAcAccucdTsdT sense
    1069-1088 3235 GAGGUGUAAUCUGUGGCUC 3236 GAGGUGuAAUCUGUGGCUCdTsdT antis
    1106-1125 3237 GGCUGGCUGUGUACUUGCU 3238 GGcuGGcuGuGuAcuuGcudTsdT sense
    1106-1125 3239 AGCAAGUACACAGCCAGCC 3240 AGcAAGuAcAcAGCcAGCCdTsdT antis
    1118-1137 3241 ACUUGCUGAGCUACUUCUC 3242 AcuuGcuGAGcuAcuucucdTsdT sense
    1118-1137 3243 GAGAAGUAGCUCAGCAAGU 3244 GAGAAGuAGCUcAGcAAGUdTsdT antis
    1135-1154 3245 UCGGCCAGCCCAUCUUCCC 3246 ucGGccAGcccAucuucccdTsdT sense
    1135-1154 3247 GGGAAGAUGGGCUGGCCGA 3248 GGGAAGAUGGGCUGGCCGAdTsdT antis
    1137-1156 3249 GGCCAGCCCAUCUUCCCUG 3250 GGccAGcccAucuucccuGdTsdT sense
    1137-1156 3251 CAGGGAAGAUGGGCUGGCC 3252 cAGGGAAGAUGGGCUGGCCdTsdT antis
    1140-1159 3253 CAGCCCAUCUUCCCUGGGG 3254 cAGcccAucuucccuGGGGdTsdT sense
    1140-1159 3255 CCCCAGGGAAGAUGGGCUG 3256 CCCcAGGGAAGAUGGGCUGdTsdT antis
    1145-1164 3257 CAUCUUCCCUGGGGACAGU 3258 cAucuucccuGGGGAcAGudTsdT sense
    1145-1164 3259 ACUGUCCCCAGGGAAGAUG 3260 ACUGUCCCcAGGGAAGAUGdTsdT antis
    1150-1169 3261 UCCCUGGGGACAGUGGGGU 3262 ucccuGGGGAcAGuGGGGudTsdT sense
    1150-1169 3263 ACCCCACUGUCCCCAGGGA 3264 ACCCcACUGUCCCcAGGGAdTsdT antis
    1270-1289 3265 AAGCUCACCCUUGGACAAA 3266 AAGcucAcccuuGGAcAAAdTsdT sense
    1270-1289 3267 UUUGUCCAAGGGUGAGCUU 3268 UUUGUCcAAGGGUGAGCUUdTsdT antis
    1296-1315 3269 AAAUCUUCAAAGACACCAC 3270 AAAucuucAAAGAcAccAcdTsdT sense
    1296-1315 3271 GUGGUGUCUUUGAAGAUUU 3272 GUGGUGUCUUUGAAGAUUUdTsdT antis
    1297-1316 3273 AAUCUUCAAAGACACCACC 3274 AAucuucAAAGAcAccAccdTsdT sense
    1297-1316 3275 GGUGGUGUCUUUGAAGAUU 3276 GGUGGUGUCUUUGAAGAUUdTsdT antis
    1302-1321 3277 UCAAAGACACCACCUGAGG 3278 ucAAAGAcAccAccuGAGGdTsdT sense
    1302-1321 3279 CCUCAGGUGGUGUCUUUGA 3280 CCUcAGGUGGUGUCUUUGAdTsdT antis
    1309-1328 3281 CACCACCUGAGGCCAUUGC 3282 cAccAccuGAGGccAuuGcdTsdT sense
    1309-1328 3283 GCAAUGGCCUCAGGUGGUG 3284 GcAAUGGCCUcAGGUGGUGdTsdT antis
    1331-1350 3285 CUGCUCUAGCCUACUGGAG 3286 cuGcucuAGccuAcuGGAGdTsdT sense
    1331-1350 3287 CUCCAGUAGGCUAGAGCAG 3288 CUCcAGuAGGCuAGAGcAGdTsdT antis
    1422-1441 3289 GGAGCCCAGCUCCCCAACG 3290 GGAGcccAGcuccccAAcGdTsdT sense
    1422-1441 3291 CGUUGGGGAGCUGGGCUCC 3292 CGUUGGGGAGCUGGGCUCCdTsdT antis
    1441-1460 3293 ACCGCCCGCUUCCCCCCCU 3294 AccGcccGcuucccccccudTsdT sense
    1441-1460 3295 AGGGGGGGAAGCGGGCGGU 3296 AGGGGGGGAAGCGGGCGGUdTsdT antis
    1475-1494 3297 UGGUGAACUGUCCAUCCAA 3298 uGGuGAAcuGuccAuccAAdTsdT sense
    1475-1494 3299 UUGGAUGGACAGUUCACCA 3300 UUGGAUGGAcAGUUcACcAdTsdT antis
    1490-1509 3301 CCAACCAUCUCUCAAUGCC 3302 ccAAccAucucucAAuGccdTsdT sense
    1490-1509 3303 GGCAUUGAGAGAUGGUUGG 3304 GGcAUUGAGAGAUGGUUGGdTsdT antis
    1543-1562 3305 GCCCUGCUUCUCCCCUCAC 3306 GcccuGcuucuccccucAcdTsdT sense
    1543-1562 3307 GUGAGGGGAGAAGCAGGGC 3308 GUGAGGGGAGAAGcAGGGCdTsdT antis
    1544-1563 3309 CCCUGCUUCUCCCCUCACC 3310 cccuGcuucuccccucAccdTsdT sense
    1544-1563 3311 GGUGAGGGGAGAAGCAGGG 3312 GGUGAGGGGAGAAGcAGGGdTsdT antis
    1545-1564 3313 CCUGCUUCUCCCCUCACCA 3314 ccuGcuucuccccucAccAdTsdT sense
    1545-1564 3315 UGGUGAGGGGAGAAGCAGG 3316 UGGUGAGGGGAGAAGcAGGdTsdT antis
    1546-1565 3317 CUGCUUCUCCCCUCACCAC 3318 cuGcuucuccccucAccAcdTsdT sense
    1546-1565 3319 GUGGUGAGGGGAGAAGCAG 3320 GUGGUGAGGGGAGAAGcAGdTsdT antis
    1550-1569 3321 UUCUCCCCUCACCACUUCC 3322 uucuccccucAccAcuuccdTsdT sense
    1550-1569 3323 GGAAGUGGUGAGGGGAGAA 3324 GGAAGUGGUGAGGGGAGAAdTsdT antis
    1559-1578 3325 CACCACUUCCUACAACCCA 3326 cAccAcuuccuAcAAcccAdTsdT sense
    1559-1578 3327 UGGGUUGUAGGAAGUGGUG 3328 UGGGUUGuAGGAAGUGGUGdTsdT antis
    1574-1593 3329 CCCAUCCUCACAAGCUUUA 3330 cccAuccucAcAAGcuuuAdTsdT sense
    1574-1593 3331 UAAAGCUUGUGAGGAUGGG 3332 uAAAGCUUGUGAGGAUGGGdTsdT antis
    1585-1604 3333 AAGCUUUAACUGAAGCUCA 3334 AAGcuuuAAcuGAAGcucAdTsdT sense
    1585-1604 3335 UGAGCUUCAGUUAAAGCUU 3336 UGAGCUUcAGUuAAAGCUUdTsdT antis
    1598-1617 3337 AGCUCAGACUGGCCAAGAU 3338 AGcucAGAcuGGccAAGAudTsdT sense
    1598-1617 3339 AUCUUGGCCAGUCUGAGCU 3340 AUCUUGGCcAGUCUGAGCUdTsdT antis
    1599-1618 3341 GCUCAGACUGGCCAAGAUU 3342 GcucAGAcuGGccAAGAuudTsdT sense
    1599-1618 3343 AAUCUUGGCCAGUCUGAGC 3344 AAUCUUGGCcAGUCUGAGCdTsdT antis
    1605-1624 3345 ACUGGCCAAGAUUGGCAGC 3346 AcuGGccAAGAuuGGcAGcdTsdT sense
    1605-1624 3347 GCUGCCAAUCUUGGCCAGU 3348 GCUGCcAAUCUUGGCcAGUdTsdT antis
    1611-1630 3349 CAAGAUUGGCAGCCAUCUG 3350 cAAGAuuGGcAGccAucuGdTsdT sense
    1611-1630 3351 CAGAUGGCUGCCAAUCUUG 3352 cAGAUGGCUGCcAAUCUUGdTsdT antis
    1612-1631 3353 AAGAUUGGCAGCCAUCUGA 3354 AAGAuuGGcAGccAucuGAdTsdT sense
    1612-1631 3355 UCAGAUGGCUGCCAAUCUU 3356 UcAGAUGGCUGCcAAUCUUdTsdT antis
    1651-1670 3357 CUAGCUCUUCCUGAGGGCC 3358 cuAGcucuuccuGAGGGccdTsdT sense
    1651-1670 3359 GGCCCUCAGGAAGAGCUAG 3360 GGCCCUcAGGAAGAGCuAGdTsdT antis
    1655-1674 3361 CUCUUCCUGAGGGCCCCAC 3362 cucuuccuGAGGGccccAcdTsdT sense
    1655-1674 3363 GUGGGGCCCUCAGGAAGAG 3364 GUGGGGCCCUcAGGAAGAGdTsdT antis
    1656-1675 3365 UCUUCCUGAGGGCCCCACC 3366 ucuuccuGAGGGccccAccdTsdT sense
    1656-1675 3367 GGUGGGGCCCUCAGGAAGA 3368 GGUGGGGCCCUcAGGAAGAdTsdT antis
    1803-1822 3369 UAGGCCUCCCUCAGCAGCC 3370 uAGGccucccucAGcAGccdTsdT sense
    1803-1822 3371 GGCUGCUGAGGGAGGCCUA 3372 GGCUGCUGAGGGAGGCCuAdTsdT antis
    1804-1823 3373 AGGCCUCCCUCAGCAGCCU 3374 AGGccucccucAGcAGccudTsdT sense
    1804-1823 3375 AGGCUGCUGAGGGAGGCCU 3376 AGGCUGCUGAGGGAGGCCUdTsdT antis
    1805-1824 3377 GGCCUCCCUCAGCAGCCUA 3378 GGccucccucAGcAGccuAdTsdT sense
    1805-1824 3379 UAGGCUGCUGAGGGAGGCC 3380 uAGGCUGCUGAGGGAGGCCdTsdT antis
    1806-1825 3381 GCCUCCCUCAGCAGCCUAA 3382 GccucccucAGcAGccuAAdTsdT sense
    1806-1825 3383 UUAGGCUGCUGAGGGAGGC 3384 UuAGGCUGCUGAGGGAGGCdTsdT antis
    1810-1829 3385 CCCUCAGCAGCCUAACCUC 3386 cccucAGcAGccuAAccucdTsdT sense
    1810-1829 3387 GAGGUUAGGCUGCUGAGGG 3388 GAGGUuAGGCUGCUGAGGGdTsdT antis
    1846-1865 3389 AGAGGAUUUUAACUGUUUG 3390 AGAGGAuuuuAAcuGuuuGdTsdT sense
    1846-1865 3391 CAAACAGUUAAAAUCCUCU 3392 cAAAcAGUuAAAAUCCUCUdTsdT antis
    1871-1890 3393 AGGGGAGAAAAGGAAGGAC 3394 AGGGGAGAAAAGGAAGGAcdTsdT sense
    1871-1890 3395 GUCCUUCCUUUUCUCCCCU 3396 GUCCUUCCUUUUCUCCCCUdTsdT antis
    1873-1892 3397 GGGAGAAAAGGAAGGACGG 3398 GGGAGAAAAGGAAGGAcGGdTsdT sense
    1873-1892 3399 CCGUCCUUCCUUUUCUCCC 3400 CCGUCCUUCCUUUUCUCCCdTsdT antis
    1877-1896 3401 GAAAAGGAAGGACGGGGUU 3402 GAAAAGGAAGGAcGGGGuudTsdT sense
    1877-1896 3403 AACCCCGUCCUUCCUUUUC 3404 AACCCCGUCCUUCCUUUUCdTsdT antis
    1933-1952 3405 CCCUCCCCCAGGCUACCAC 3406 cccucccccAGGcuAccAcdTsdT sense
    1933-1952 3407 GUGGUAGCCUGGGGGAGGG 3408 GUGGuAGCCUGGGGGAGGGdTsdT antis
    1934-1953 3409 CCUCCCCCAGGCUACCACU 3410 ccucccccAGGcuAccAcudTsdT sense
    1934-1953 3411 AGUGGUAGCCUGGGGGAGG 3412 AGUGGuAGCCUGGGGGAGGdTsdT antis
    1940-1959 3413 CCAGGCUACCACUCCUUCC 3414 ccAGGcuAccAcuccuuccdTsdT sense
    1940-1959 3415 GGAAGGAGUGGUAGCCUGG 3416 GGAAGGAGUGGuAGCCUGGdTsdT antis
    1941-1960 3417 CAGGCUACCACUCCUUCCC 3418 cAGGcuAccAcuccuucccdTsdT sense
    1941-1960 3419 GGGAAGGAGUGGUAGCCUG 3420 GGGAAGGAGUGGuAGCCUGdTsdT antis
    1945-1964 3421 CUACCACUCCUUCCCUCCC 3422 cuAccAcuccuucccucccdTsdT sense
    1945-1964 3423 GGGAGGGAAGGAGUGGUAG 3424 GGGAGGGAAGGAGUGGuAGdTsdT antis
    1946-1965 3425 UACCACUCCUUCCCUCCCC 3426 uAccAcuccuucccuccccdTsdT sense
    1946-1965 3427 GGGGAGGGAAGGAGUGGUA 3428 GGGGAGGGAAGGAGUGGuAdTsdT antis
    1953-1972 3429 CCUUCCCUCCCCCCCUCUC 3430 ccuucccucccccccucucdTsdT sense
    1953-1972 3431 GAGAGGGGGGGAGGGAAGG 3432 GAGAGGGGGGGAGGGAAGGdTsdT antis
    2023-2042 3433 CCUGGCCCCCUGGGUGUAA 3434 ccuGGcccccuGGGuGuAAdTsdT sense
    2023-2042 3435 UUACACCCAGGGGGCCAGG 3436 UuAcACCcAGGGGGCcAGGdTsdT antis
    2024-2043 3437 CUGGCCCCCUGGGUGUAAA 3438 cuGGcccccuGGGuGuAAAdTsdT sense
    2024-2043 3439 UUUACACCCAGGGGGCCAG 3440 UUuAcACCcAGGGGGCcAGdTsdT antis
    2040-2059 3441 AAAUAGAUUGUUAUAAUUU 3442 AAAuAGAuuGuuAuAAuuudTsdT sense
    2040-2059 3443 AAAUUAUAACAAUCUAUUU 3444 AAAUuAuAAcAAUCuAUUUdTsdT antis
    2043-2062 3445 UAGAUUGUUAUAAUUUUUU 3446 uAGAuuGuuAuAAuuuuuudTsdT sense
    2043-2062 3447 AAAAAAUUAUAACAAUCUA 3448 AAAAAAUuAuAAcAAUCuAdTsdT antis
    2044-2063 3449 AGAUUGUUAUAAUUUUUUC 3450 AGAuuGuuAuAAuuuuuucdTsdT sense
    2044-2063 3451 GAAAAAAUUAUAACAAUCU 3452 GAAAAAAUuAuAAcAAUCUdTsdT antis
    2045-2064 3453 GAUUGUUAUAAUUUUUUCU 3454 GAuuGuuAuAAuuuuuucudTsdT sense
    2045-2064 3455 AGAAAAAAUUAUAACAAUC 3456 AGAAAAAAUuAuAAcAAUCdTsdT antis
    2046-2065 3457 AUUGUUAUAAUUUUUUCUU 3458 AuuGuuAuAAuuuuuucuudTsdT sense
    2046-2065 3459 AAGAAAAAAUUAUAACAAU 3460 AAGAAAAAAUuAuAAcAAUdTsdT antis
    2049-2068 3461 GUUAUAAUUUUUUCUUAAA 3462 GuuAuAAuuuuuucuuAAAdTsdT sense
    2049-2068 3463 UUUAAGAAAAAAUUAUAAC 3464 UUuAAGAAAAAAUuAuAACdTsdT antis
    2117-2136 3465 UCUUGUCCUCUGCUCCCAA 3466 ucuuGuccucuGcucccAAdTsdT sense
    2117-2136 3467 UUGGGAGCAGAGGACAAGA 3468 UUGGGAGcAGAGGAcAAGAdTsdT antis
    2118-2137 3469 CUUGUCCUCUGCUCCCAAG 3470 cuuGuccucuGcucccAAGdTsdT sense
    2118-2137 3471 CUUGGGAGCAGAGGACAAG 3472 CUUGGGAGcAGAGGAcAAGdTsdT antis
    2129-2148 3473 CUCCCAAGGCUUCCUCCCU 3474 cucccAAGGcuuccucccudTsdT sense
    2129-2148 3475 AGGGAGGAAGCCUUGGGAG 3476 AGGGAGGAAGCCUUGGGAGdTsdT antis
    2130-2149 3477 UCCCAAGGCUUCCUCCCUC 3478 ucccAAGGcuuccucccucdTsdT sense
    2130-2149 3479 GAGGGAGGAAGCCUUGGGA 3480 GAGGGAGGAAGCCUUGGGAdTsdT antis
    2133-2152 3481 CAAGGCUUCCUCCCUCUCC 3482 cAAGGcuuccucccucuccdTsdT sense
    2133-2152 3483 GGAGAGGGAGGAAGCCUUG 3484 GGAGAGGGAGGAAGCCUUGdTsdT antis
    2134-2153 3485 AAGGCUUCCUCCCUCUCCC 3486 AAGGcuuccucccucucccdTsdT sense
    2134-2153 3487 GGGAGAGGGAGGAAGCCUU 3488 GGGAGAGGGAGGAAGCCUUdTsdT antis
    2146-2165 3489 CUCUCCCCAUCCUGGAAGG 3490 cucuccccAuccuGGAAGGdTsdT sense
    2146-2165 3491 CCUUCCAGGAUGGGGAGAG 3492 CCUUCcAGGAUGGGGAGAGdTsdT antis
    2150-2169 3493 CCCCAUCCUGGAAGGAGGG 3494 ccccAuccuGGAAGGAGGGdTsdT sense
    2150-2169 3495 CCCUCCUUCCAGGAUGGGG 3496 CCCUCCUUCcAGGAUGGGGdTsdT antis
    2152-2171 3497 CCAUCCUGGAAGGAGGGGA 3498 ccAuccuGGAAGGAGGGGAdTsdT sense
    2152-2171 3499 UCCCCUCCUUCCAGGAUGG 3500 UCCCCUCCUUCcAGGAUGGdTsdT antis
    2156-2175 3501 CCUGGAAGGAGGGGAGUAG 3502 ccuGGAAGGAGGGGAGuAGdTsdT sense
    2156-2175 3503 CUACUCCCCUCCUUCCAGG 3504 CuACUCCCCUCCUUCcAGGdTsdT antis
    2161-2180 3505 AAGGAGGGGAGUAGAGAGA 3506 AAGGAGGGGAGuAGAGAGAdTsdT sense
    2161-2180 3507 UCUCUCUACUCCCCUCCUU 3508 UCUCUCuACUCCCCUCCUUdTsdT antis
    2208-2227 3509 GGUUUGCCUGUGUACAGAC 3510 GGuuuGccuGuGuAcAGAcdTsdT sense
    2208-2227 3511 GUCUGUACACAGGCAAACC 3512 GUCUGuAcAcAGGcAAACCdTsdT antis
    2219-2238 3513 GUACAGACCUCUGUUCAAU 3514 GuAcAGAccucuGuucAAudTsdT sense
    2219-2238 3515 AUUGAACAGAGGUCUGUAC 3516 AUUGAAcAGAGGUCUGuACdTsdT antis
    2233-2252 3517 UCAAUAAAUUAUUGGCAUG 3518 ucAAuAAAuuAuuGGcAuGdTsdT sense
    2233-2252 3519 CAUGCCAAUAAUUUAUUGA 3520 cAUGCcAAuAAUUuAUUGAdTsdT antis
     2-21 3521 UGGUGACAACGAAGCCGAC 3522 uGGuGAcAAcGAAGccGAcdTsdT sense
     2-21 3523 GUCGGCUUCGUUGUCACCA 3524 GUCGGCUUCGUUGUcACcAdTsdT antis
    138-157 3525 GCGGGGGCAGCCCAGGCAG 3526 GcGGGGGcAGcccAGGcAGdTsdT sense
    138-157 3527 CUGCCUGGGCUGCCCCCGC 3528 CUGCCUGGGCUGCCCCCGCdTsdT antis
    381-400 3529 AGCUCCGGGGGUGGCCCCA 3530 AGcuccGGGGGuGGccccAdTsdT sense
    381-400 3531 UGGGGCCACCCCCGGAGCU 3532 UGGGGCcACCCCCGGAGCUdTsdT antis
    592-611 3533 ACCAGGCACGGCUGGCAGA 3534 AccAGGcAcGGcuGGcAGAdTsdT sense
    592-611 3535 UCUGCCAGCCGUGCCUGGU 3536 UCUGCcAGCCGUGCCUGGUdTsdT antis
    615-634 3537 AGGGAACUGGUGGCCAUCA 3538 AGGGAAcuGGuGGccAucAdTsdT sense
    615-634 3539 UGAUGGCCACCAGUUCCCU 3540 UGAUGGCcACcAGUUCCCUdTsdT antis
    1026-1045 3541 UACAUCUGCUCUCGGUACU 3542 uAcAucuGcucucGGuAcudTsdT sense
    1026-1045 3543 AGUACCGAGAGCAGAUGUA 3544 AGuACCGAGAGcAGAUGuAdTsdT antis
    1027-1046 3545 ACAUCUGCUCUCGGUACUA 3546 AcAucuGcucucGGuAcuAdTsdT sense
    1027-1046 3547 UAGUACCGAGAGCAGAUGU 3548 uAGuACCGAGAGcAGAUGUdTsdT antis
    1105-1124 3549 CGGCUGGCUGUGUACUUGC 3550 cGGcuGGcuGuGuAcuuGcdTsdT sense
    1105-1124 3551 GCAAGUACACAGCCAGCCG 3552 GcAAGuAcAcAGCcAGCCGdTsdT antis
    1362-1381 3553 UCAAGGCUCUCCCCACUCG 3554 ucAAGGcucuccccAcucGdTsdT sense
    1362-1381 3555 CGAGUGGGGAGAGCCUUGA 3556 CGAGUGGGGAGAGCCUUGAdTsdT antis
    1440-1459 3557 GACCGCCCGCUUCCCCCCC 3558 GAccGcccGcuucccccccdTsdT sense
    1440-1459 3559 GGGGGGGAAGCGGGCGGUC 3560 GGGGGGGAAGCGGGCGGUCdTsdT antis
    2017-2036 3561 CCCUUCCCUGGCCCCCUGG 3562 cccuucccuGGcccccuGGdTsdT sense
    2017-2036 3563 CCAGGGGGCCAGGGAAGGG 3564 CcAGGGGGCcAGGGAAGGGdTsdT antis
    2018-2037 3565 CCUUCCCUGGCCCCCUGGG 3566 ccuucccuGGcccccuGGGdTsdT sense
    2018-2037 3567 CCCAGGGGGCCAGGGAAGG 3568 CCcAGGGGGCcAGGGAAGGdTsdT antis
    2019-2038 3569 CUUCCCUGGCCCCCUGGGU 3570 cuucccuGGcccccuGGGudTsdT sense
    2019-2038 3571 ACCCAGGGGGCCAGGGAAG 3572 ACCcAGGGGGCcAGGGAAGdTsdT antis
    2148-2167 3573 CUCCCCAUCCUGGAAGGAG 3574 cuccccAuccuGGAAGGAGdTsdT sense
    2148-2167 3575 CUCCUUCCAGGAUGGGGAG 3576 CUCCUUCcAGGAUGGGGAGdTsdT antis
    2149-2168 3577 UCCCCAUCCUGGAAGGAGG 3578 uccccAuccuGGAAGGAGGdTsdT sense
    2149-2168 3579 CCUCCUUCCAGGAUGGGGA 3580 CCUCCUUCcAGGAUGGGGAdTsdT antis
    1335-1354 3581 UCUAGCCUACUGGAGUACA 3582 ucuAGccuAcuGGAGuAcAdTsdT sense
    1335-1354 3583 UGUACUCCAGUAGGCUAGA 3584 UGuACUCcAGuAGGCuAGAdTsdT antis
    342-361 3585 GCGUCAGUCGGGGCUAUGG 3586 GcGucAGucGGGGcuAuGGdTsdT sense
    342-361 3587 CCAUAGCCCCGACUGACGC 3588 CcAuAGCCCCGACUGACGCdTsdT antis
    675-694 3589 CAGAUUAUGCGUAAGCUGG 3590 cAGAuuAuGcGuAAGcuGGdTsdT sense
    675-694 3591 CCAGCUUACGCAUAAUCUG 3592 CcAGCUuACGcAuAAUCUGdTsdT antis
    1080-1099 3593 UACACCUCGUCCAUCGAUG 3594 uAcAccucGuccAucGAuGdTsdT sense
    1080-1099 3595 CAUCGAUGGACGAGGUGUA 3596 cAUCGAUGGACGAGGUGuAdTsdT antis
    333-352 3597 GGCGGGAAAGCGUCAGUCG 3598 GGcGGGAAAGcGucAGucGdTsdT sense
    333-352 3599 CGACUGACGCUUUCCCGCC 3600 CGACUGACGCUUUCCCGCCdTsdT antis
    475-494 3601 GUGACAGCGGGAAGGUGAC 3602 GuGAcAGcGGGAAGGuGAcdTsdT sense
    475-494 3603 GUCACCUUCCCGCUGUCAC 3604 GUcACCUUCCCGCUGUcACdTsdT antis
    533-552 3605 CCAAGAAGUGGCUUACACU 3606 ccAAGAAGuGGcuuAcAcudTsdT sense
    533-552 3607 AGUGUAAGCCACUUCUUGG 3608 AGUGuAAGCcACUUCUUGGdTsdT antis
    746-765 3609 GAAGGACGAGCUGUAUUUG 3610 GAAGGAcGAGcuGuAuuuGdTsdT sense
    746-765 3611 CAAAUACAGCUCGUCCUUC 3612 cAAAuAcAGCUCGUCCUUCdTsdT antis
    747-766 3613 AAGGACGAGCUGUAUUUGA 3614 AAGGAcGAGcuGuAuuuGAdTsdT sense
    747-766 3615 UCAAAUACAGCUCGUCCUU 3616 UcAAAuAcAGCUCGUCCUUdTsdT antis
    830-849 3617 GCUGAUCACCCCUAUCAUC 3618 GcuGAucAccccuAucAucdTsdT sense
    830-849 3619 GAUGAUAGGGGUGAUCAGC 3620 GAUGAuAGGGGUGAUcAGCdTsdT antis
    1334-1353 3621 CUCUAGCCUACUGGAGUAC 3622 cucuAGccuAcuGGAGuAcdTsdT sense
    1334-1353 3623 GUACUCCAGUAGGCUAGAG 3624 GuACUCcAGuAGGCuAGAGdTsdT antis
    497-516 3625 AGUGGUAGCCACUGUAGGC 3626 AGuGGuAGccAcuGuAGGcdTsdT sense
    497-516 3627 GCCUACAGUGGCUACCACU 3628 GCCuAcAGUGGCuACcACUdTsdT antis
    1641-1660 3629 GCUACCCUCGCUAGCUCUU 3630 GcuAcccucGcuAGcucuudTsdT sense
    1641-1660 3631 AAGAGCUAGCGAGGGUAGC 3632 AAGAGCuAGCGAGGGuAGCdTsdT antis
    1642-1661 3633 CUACCCUCGCUAGCUCUUC 3634 cuAcccucGcuAGcucuucdTsdT sense
    1642-1661 3635 GAAGAGCUAGCGAGGGUAG 3636 GAAGAGCuAGCGAGGGuAGdTsdT antis
    676-695 3637 AGAUUAUGCGUAAGCUGGA 3638 AGAuuAuGcGuAAGcuGGAdTsdT sense
    676-695 3639 UCCAGCUUACGCAUAAUCU 3640 UCcAGCUuACGcAuAAUCUdTsdT antis
    1128-1147 3641 CUACUUCUCGGCCAGCCCA 3642 cuAcuucucGGccAGcccAdTsdT sense
    1128-1147 3643 UGGGCUGGCCGAGAAGUAG 3644 UGGGCUGGCCGAGAAGuAGdTsdT antis
    40-59 3645 CCGGCGUGCCCCGCGGCGG 3646 ccGGcGuGccccGcGGcGGdTsdT sense
    40-59 3647 CCGCCGCGGGGCACGCCGG 3648 CCGCCGCGGGGcACGCCGGdTsdT antis
    199-218 3649 GCGGCGGGCCUUCGGGAGG 3650 GcGGcGGGccuucGGGAGGdTsdT sense
    199-218 3651 CCUCCCGAAGGCCCGCCGC 3652 CCUCCCGAAGGCCCGCCGCdTsdT antis
    222-241 3653 CCUGGGGGCUCGGGCCGGG 3654 ccuGGGGGcucGGGccGGGdTsdT sense
    222-241 3655 CCCGGCCCGAGCCCCCAGG 3656 CCCGGCCCGAGCCCCcAGGdTsdT antis
    343-362 3657 CGUCAGUCGGGGCUAUGGG 3658 cGucAGucGGGGcuAuGGGdTsdT sense
    343-362 3659 CCCAUAGCCCCGACUGACG 3660 CCcAuAGCCCCGACUGACGdTsdT antis
    437-456 3661 GGGCACUAGCUUCCCGCCG 3662 GGGcAcuAGcuucccGccGdTsdT sense
    437-456 3663 CGGCGGGAAGCUAGUGCCC 3664 CGGCGGGAAGCuAGUGCCCdTsdT antis
    538-557 3665 AAGUGGCUUACACUGACAU 3666 AAGuGGcuuAcAcuGAcAudTsdT sense
    538-557 3667 AUGUCAGUGUAAGCCACUU 3668 AUGUcAGUGuAAGCcACUUdTsdT antis
    663-682 3669 AACCGAGAACUGCAGAUUA 3670 AAccGAGAAcuGcAGAuuAdTsdT sense
    663-682 3671 UAAUCUGCAGUUCUCGGUU 3672 uAAUCUGcAGUUCUCGGUUdTsdT antis
    887-906 3673 GGCCUACAUCCACUCCCAA 3674 GGccuAcAuccAcucccAAdTsdT sense
    687-906 3675 UUGGGAGUGGAUGUAGGCC 3676 UUGGGAGUGGAUGuAGGCCdTsdT antis
     997-1016 3677 AGCUGGUUCGGGGGGAGCC 3678 AGcuGGuucGGGGGGAGccdTsdT sense
     997-1016 3679 GGCUCCCCCCGAACCAGCU 3680 GGCUCCCCCCGAACcAGCUdTsdT antis
    1079-1098 3681 UUACACCUCGUCCAUCGAU 3682 uuAcAccucGuccAucGAudTsdT sense
    1079-1098 3683 AUCGAUGGACGAGGUGUAA 3684 AUCGAUGGACGAGGUGuAAdTsdT antis
    1323-1342 3685 AUUGCACUCUGCUCUAGCC 3686 AuuGcAcucuGcucuAGccdTsdT sense
    1323-1342 3687 GGCUAGAGCAGAGUGCAAU 3688 GGCuAGAGcAGAGUGcAAUdTsdT antis
    1370-1389 3689 CUCCCCACUCGAGGCUUGU 3690 cuccccAcucGAGGcuuGudTsdT sense
    1370-1389 3691 ACAAGCCUCGAGUGGGGAG 3692 AcAAGCCUCGAGUGGGGAGdTsdT antis
    1494-1513 3693 CCAUCUCUCAAUGCCAUUC 3694 ccAucucucAAuGccAuucdTsdT sense
    1494-1513 3695 GAAUGGCAUUGAGAGAUGG 3696 GAAUGGcAUUGAGAGAUGGdTsdT antis
    57-76 3697 GGGCGCUGGGCCGGAGCCG 3698 GGGcGcuGGGccGGAGccGdTsdT sense
    57-76 3699 CGGCUCCGGCCCAGCGCCC 3700 CGGCUCCGGCCcAGCGCCCdTsdT antis
    137-156 3701 GGCGGGGGCAGCCCAGGCA 3702 GGcGGGGGcAGcccAGGcAdTsdT sense
    137-156 3703 UGCCUGGGCUGCCCCCGCC 3704 UGCCUGGGCUGCCCCCGCCdTsdT antis
    141-160 3705 GGGGCAGCCCAGGCAGCCC 3706 GGGGcAGcccAGGcAGcccdTsdT sense
    141-160 3707 GGGCUGCCUGGGCUGCCCC 3708 GGGCUGCCUGGGCUGCCCCdTsdT antis
    198-217 3709 GGCGGCGGGCCUUCGGGAG 3710 GGcGGcGGGccuucGGGAGdTsdT sense
    198-217 3711 CUCCCGAAGGCCCGCCGCC 3712 CUCCCGAAGGCCCGCCGCCdTsdT antis
    319-338 3713 CAGGAGGCACUGGCGGCGG 3714 cAGGAGGcAcuGGcGGcGGdTsdT sense
    319-338 3715 CCGCCGCCAGUGCCUCCUG 3710 CCGCCGCcAGUGCCUCCUGdTsdT antis
    417-436 3717 GGCAGCGGUGGCCCCGGCG 3718 GGcAGcGGuGGccccGGcGdTsdT sense
    417-436 3719 CGCCGGGGCCACCGCUGCC 3720 CGCCGGGGCcACCGCUGCCdTsdT antis
    490-509 3721 UGACCACAGUGGUAGCCAC 3722 uGAccAcAGuGGuAGccAcdTsdT sense
    490-509 3723 GUGGCUACCACUGUGGUCA 3724 GUGGCuACcACUGUGGUcAdTsdT antis
    503-522 3725 AGCCACUGUAGGCCAAGGC 3726 AGccAcuGuAGGccAAGGcdTsdT sense
    503-522 3727 GCCUUGGCCUACAGUGGCU 3728 GCCUUGGCCuAcAGUGGCUdTsdT antis
    539-558 3729 AGUGGCUUACACUGACAUC 3730 AGuGGcuuAcAcuGAcAucdTsdT sense
    539-558 3731 GAUGUCAGUGUAAGCCACU 3732 GAUGUcAGUGuAAGCcACUdTsdT antis
    602-621 3733 GCUGGCAGAGACGAGGGAA 3734 GcuGGcAGAGAcGAGGGAAdTsdT sense
    602-621 3735 UUCCCUCGUCUCUGCCAGC 3736 UUCCCUCGUCUCUGCcAGCdTsdT antis
    793-812 3737 CGGUGUACCGAGUGGCCCG 3738 cGGuGuAccGAGuGGcccGdTsdT sense
    793-812 3739 CGGGCCACUCGGUACACCG 3740 CGGGCcACUCGGuAcACCGdTsdT antis
    825-844 3741 GCCAAGCUGAUCACCCCUA 3742 GccAAGcuGAucAccccuAdTsdT sense
    825-844 3743 UAGGGGUGAUCAGCUUGGC 3744 uAGGGGUGAUcAGCUUGGCdTsdT antis
    829-848 3745 AGCUGAUCACCCCUAUCAU 3746 AGcuGAucAccccuAucAudTsdT sense
    829-848 3747 AUGAUAGGGGUGAUCAGCU 3748 AUGAuAGGGGUGAUcAGCUdTsdT antis
    843-862 3749 AUCAUCUACAUCAAGGUGU 3750 AucAucuAcAucAAGGuGudTsdT sense
    843-862 3751 ACACCUUGAUGUAGAUGAU 3752 AcACCUUGAUGuAGAUGAUdTsdT antis
    844-863 3753 UCAUCUACAUCAAGGUGUA 3754 ucAucuAcAucAAGGuGuAdTsdT sense
    844-863 3755 UACACCUUGAUGUAGAUGA 3756 uAcACCUUGAUGuAGAUGAdTsdT antis
    888-907 3757 GCCUACAUCCACUCCCAAG 3758 GccuAcAuccAcucccAAGdTsdT sense
    888-907 3759 CUUGGGAGUGGAUGUAGGC 3760 CUUGGGAGUGGAUGuAGGCdTsdT antis
    902-921 3761 CCAAGGUGUGUGUCACCGU 3762 ccAAGGuGuGuGucAccGudTsdT sense
    902-921 3763 ACGGUGACACACACCUUGG 3764 ACGGUGAcAcAcACCUUGGdTsdT antis
    1067-1086 3765 UGGAGCCACAGAUUACACC 3766 uGGAGccAcAGAuuAcAccdTsdT sense
    1067-1086 3767 GGUGUAAUCUGUGGCUCCA 3768 GGUGuAAUCUGUGGCUCcAdTsdT antis
    1095-1114 3769 GAUGUGUGGUCGGCUGGCU 3770 GAuGuGuGGucGGcuGGcudTsdT sense
    1095-1114 3771 AGCCAGCCGACCACACAUC 3772 AGCcAGCCGACcAcAcAUCdTsdT antis
    1154-1173 3773 UGGGGACAGUGGGGUGGAC 3774 uGGGGAcAGuGGGGuGGAcdTsdT sense
    1154-1173 3775 GUCCACCCCACUGUCCCCA 3776 GUCcACCCcACUGUCCCcAdTsdT antis
    1271-1290 3777 AGCUCACCCUUGGACAAAG 3778 AGcucAcccuuGGAcAAAGdTsdT sense
    1271-1290 3779 CUUUGUCCAAGGGUGAGCU 3780 CUUUGUCcAAGGGUGAGCUdTsdT antis
    1272-1291 3781 GCUCACCCUUGGACAAAGG 3782 GcucAcccuuGGAcAAAGGdTsdT sense
    1272-1291 3783 CCUUUGUCCAAGGGUGAGC 3784 CCUUUGUCcAAGGGUGAGCdTsdT antis
    1289-1308 3785 GGUGUUCAAAUCUUCAAAG 3786 GGuGuucAAAucuucAAAGdTsdT sense
    1289-1308 3787 CUUUGAAGAUUUGAACACC 3788 CUUUGAAGAUUUGAAcACCdTsdT antis
    1324-1343 3789 UUGCACUCUGCUCUAGCCU 3790 uuGcAcucuGcucuAGccudTsdT sense
    1324-1343 3791 AGGCUAGAGCAGAGUGCAA 3792 AGGCuAGAGcAGAGUGcAAdTsdT antis
    1351-1370 3793 ACACGCCAUCCUCAAGGCU 3794 AcAcGccAuccucAAGGcudTsdT sense
    1351-1370 3795 AGCCUUGAGGAUGGCGUGU 3796 AGCCUUGAGGAUGGCGUGUdTsdT antis
    1371-1390 3797 UCCCCACUCGAGGCUUGUG 3798 uccccAcucGAGGcuuGuGdTsdT sense
    1371-1390 3799 CACAAGCCUCGAGUGGGGA 3800 cAcAAGCCUCGAGUGGGGAdTsdT antis
    1392-1411 3801 CACAGCUUCUUCGAUGAAC 3802 cAcAGcuucuucGAuGAAcdTsdT sense
    1392-1411 3803 GUUCAUCGAAGAAGCUGUG 3804 GUUcAUCGAAGAAGCUGUGdTsdT antis
    1395-1414 3805 AGCUUCUUCGAUGAACUGC 3806 AGcuucuucGAuGAAcuGcdTsdT sense
    1395-1414 3807 GCAGUUCAUCGAAGAAGCU 3808 GcAGUUcAUCGAAGAAGCUdTsdT antis
    1439-1458 3809 CGACCGCCCGCUUCCCCCC 3810 cGAccGcccGcuuccccccdTsdT sense
    1439-1458 3811 GGGGGGAAGCGGGCGGUCG 3812 GGGGGGAAGCGGGCGGUCGdTsdT antis
    1442-1461 3813 CCGCCCGCUUCCCCCCCUG 3814 ccGcccGcuucccccccuGdTsdT sense
    1442-1461 3815 CAGGGGGGGAAGCGGGCGG 3816 cAGGGGGGGAAGCGGGCGGdTsdT antis
    1467-1486 3817 UUCAGUCCUGGUGAACUGU 3818 uucAGuccuGGuGAAcuGudTsdT sense
    1467-1486 3819 ACAGUUCACCAGGACUGAA 3820 AcAGUUcACcAGGACUGAAdTsdT antis
    1468-1487 3821 UCAGUCCUGGUGAACUGUC 3822 ucAGuccuGGuGAAcuGucdTsdT sense
    1468-1487 3823 GACAGUUCACCAGGACUGA 3824 GAcAGUUcACcAGGACUGAdTsdT antis
    1482-1501 3825 CUGUCCAUCCAACCAUCUC 3826 cuGuccAuccAAccAucucdTsdT sense
    1482-1501 3827 GAGAUGGUUGGAUGGACAG 3828 GAGAUGGUUGGAUGGAcAGdTsdT antis
    1483-1502 3829 UGUCCAUCCAACCAUCUCU 3830 uGuccAuccAAccAucucudTsdT sense
    1483-1502 3831 AGAGAUGGUUGGAUGGACA 3832 AGAGAUGGUUGGAUGGAcAdTsdT antis
    1495-1514 3833 CAUCUCUCAAUGCCAUUCU 3834 cAucucucAAuGccAuucudTsdT sense
    1495-1514 3835 AGAAUGGCAUUGAGAGAUG 3836 AGAAUGGcAUUGAGAGAUGdTsdT antis
    1554-1573 3837 CCCCUCACCACUUCCUACA 3838 ccccucAccAcuuccuAcAdTsdT sense
    1554-1573 3839 UGUAGGAAGUGGUGAGGGG 3840 UGuAGGAAGUGGUGAGGGGdTsdT antis
    1597-1616 3841 AAGCUCAGACUGGCCAAGA 3842 AAGcucAGAcuGGccAAGAdTsdT sense
    1597-1616 3843 UCUUGGCCAGUCUGAGCUU 3844 UCUUGGCcAGUCUGAGCUUdTsdT antis
    1659-1678 3845 UCCUGAGGGCCCCACCGAC 3846 uccuGAGGGccccAccGAcdTsdT sense
    1659-1678 3847 GUCGGUGGGGCCCUCAGGA 3848 GUCGGUGGGGCCCUcAGGAdTsdT antis
    1814-1833 3849 CAGCAGCCUAACCUCUGUG 3850 cAGcAGccuAAccucuGuGdTsdT sense
    1814-1833 3851 CACAGAGGUUAGGCUGCUG 3852 cAcAGAGGUuAGGCUGCUGdTsdT antis
    1815-1834 3853 AGCAGCCUAACCUCUGUGG 3854 AGcAGccuAAccucuGuGGdTsdT sense
    1815-1834 3855 CCACAGAGGUUAGGCUGCU 3856 CcAcAGAGGUuAGGCUGCUdTsdT antis
    1904-1923 3857 UGAGGACCUUCUACCCCCU 3858 uGAGGAccuucuAcccccudTsdT sense
    1904-1923 3859 AGGGGGUAGAAGGUCCUCA 3860 AGGGGGuAGAAGGUCCUcAdTsdT antis
    1905-1924 3861 GAGGACCUUCUACCCCCUU 3862 GAGGAccuucuAcccccuudTsdT sense
    1905-1924 3863 AAGGGGGUAGAAGGUCCUC 3864 AAGGGGGuAGAAGGUCCUCdTsdT antis
    2012-2031 3865 GUCUUCCCUUCCCUGGCCC 3866 GucuucccuucccuGGcccdTsdT sense
    2012-2031 3867 GGGCCAGGGAAGGGAAGAC 3868 GGGCcAGGGAAGGGAAGACdTsdT antis
    2095-2114 3869 UGCCCCCCCCAGCUGUACC 3870 uGccccccccAGcuGuAccdTsdT sense
    2095-2114 3871 GGUACAGCUGGGGGGGGCA 3872 GGuAcAGCUGGGGGGGGcAdTsdT antis
    2102-2121 3873 CCCAGCUGUACCCCUUCUU 3874 cccAGcuGuAccccuucuudTsdT sense
    2102-2121 3875 AAGAAGGGGUACAGCUGGG 3876 AAGAAGGGGuAcAGCUGGGdTsdT antis
    2184-2203 3877 CUGGUGUCUUAGUUUCCAC 3878 cuGGuGucuuAGuuuccAcdTsdT sense
    2184-2203 3879 GUGGAAACUAAGACACCAG 3880 GUGGAAACuAAGAcACcAGdTsdT antis
    2192-2211 3881 UUAGUUUCCACAGUAAGGU 3882 uuAGuuuccAcAGuAAGGudTsdT sense
    2192-2211 3883 ACCUUACUGUGGAAACUAA 3884 ACCUuACUGUGGAAACuAAdTsdT antis
    2227-2246 3885 CUCUGUUCAAUAAAUUAUU 3886 cucuGuucAAuAAAuuAuudTsdT sense
    2227-2246 3887 AAUAAUUUAUUGAACAGAG 3888 AAuAAUUuAUUGAAcAGAGdTsdT antis
    151-170 3889 AGGCAGCCCGAGCCCCGCG 3890 AGGcAGcccGAGccccGcGdTsdT sense
    151-170 3891 CGCGGGGCUCGGGCUGCCU 3892 CGCGGGGCUCGGGCUGCCUdTsdT antis
    404-423 3893 CAGCGGCGGAGGAGGCAGC 3894 cAGcGGcGGAGGAGGcAGcdTsdT sense
    404-423 3895 GCUGCCUCCUCCGCCGCUG 3896 GCUGCCUCCUCCGCCGCUGdTsdT antis
    530-549 3897 UUCCCAAGAAGUGGCUUAC 3898 uucccAAGAAGuGGcuuAcdTsdT sense
    530-549 3899 GUAAGCCACUUCUUGGGAA 3900 GuAAGCcACUUCUUGGGAAdTsdT antis
    954-973 3901 GACACUGCUGUCCUCAAGC 3902 GAcAcuGcuGuccucAAGcdTsdT sense
    954-973 3903 GCUUGAGGACAGCAGUGUC 3904 GCUUGAGGAcAGcAGUGUCdTsdT antis
    1394-1413 3905 CAGCUUCUUCGAUGAACUG 3906 cAGcuucuucGAuGAAcuGdTsdT sense
    1394-1413 3907 CAGUUCAUCGAAGAAGCUG 3908 cAGUUcAUCGAAGAAGCUGdTsdT antis
    2002-2021 3909 CCCAUCUCUCGUCUUCCCU 3910 cccAucucucGucuucccudTsdT sense
    2002-2021 3911 AGGGAAGACGAGAGAUGGG 3912 AGGGAAGACGAGAGAUGGGdTsdT antis
    2003-2022 3913 CCAUCUCUCGUCUUCCCUU 3914 ccAucucucGucuucccuudTsdT sense
    2003-2022 3915 AAGGGAAGACGAGAGAUGG 3916 AAGGGAAGACGAGAGAUGGdTsdT antis
    2121-2140 3917 GUCCUCUGCUCCCAAGGCU 3918 GuccucuGcucccAAGGcudTsdT sense
    2121-2140 3919 AGCCUUGGGAGCAGAGGAC 3920 AGCCUUGGGAGcAGAGGACdTsdT antis
    24-43 3921 AGAGGGACUUCAUCUCCCG 3922 AGAGGGAcuucAucucccGdTsdT sense
    24-43 3923 CGGGAGAUGAAGUCCCUCU 3924 CGGGAGAUGAAGUCCCUCUdTsdT antis
    49-68 3925 CCCGCGGCGGGCGCUGGGC 3926 cccGcGGcGGGcGcuGGGcdTsdT sense
    49-68 3927 GCCCAGCGCCCGCCGCGGG 3928 GCCcAGCGCCCGCCGCGGGdTsdT antis
    107-126 3929 GAGCCCAGGGGAGGCGGCG 3930 GAGcccAGGGGAGGcGGcGdTsdT sense
    107-126 3931 CGCCGCCUCCCCUGGGCUC 3932 CGCCGCCUCCCCUGGGCUCdTsdT antis
    126-145 3933 GCAGAGGCAGCGGCGGGGG 3934 GcAGAGGcAGcGGcGGGGGdTsdT sense
    126-145 3935 CCCCCGCCGCUGCCUCUGC 3936 CCCCCGCCGCUGCCUCUGCdTsdT antis
    153-172 3937 GCAGCCCGAGCCCCGCGGC 3938 GcAGcccGAGccccGcGGcdTsdT sense
    153-172 3939 GCCGCGGGGCUCGGGCUGC 3940 GCCGCGGGGCUCGGGCUGCdTsdT antis
    259-278 3941 CGGAGCCAGGAGGCGGAGG 3942 cGGAGccAGGAGGcGGAGGdTsdT sense
    259-278 3943 CCUCCGCCUCCUGGCUCCG 3944 CCUCCGCCUCCUGGCUCCGdTsdT antis
    261-280 3945 GAGCCAGGAGGCGGAGGCG 3946 GAGccAGGAGGcGGAGGcGdTsdT sense
    261-280 3947 CGCCUCCGCCUCCUGGCUC 3948 CGCCUCCGCCUCCUGGCUCdTsdT antis
    512-531 3949 AGGCCAAGGCCCAGAGCGU 3950 AGGccAAGGcccAGAGcGudTsdT sense
    512-531 3951 ACGCUCUGGGCCUUGGCCU 3952 ACGCUCUGGGCCUUGGCCUdTsdT antis
    660-679 3953 AAGAACCGAGAACUGCAGA 3954 AAGAAccGAGAAcuGcAGAdTsdT sense
    660-679 3955 UCUGCAGUUCUCGGUUCUU 3956 UCUGcAGUUCUCGGUUCUUdTsdT antis
    709-728 3957 UGAGGCUGCGGUACUUUUU 3958 uGAGGcuGcGGuAcuuuuudTsdT sense
    709-728 3959 AAAAAGUACCGCAGCCUCA 3960 AAAAAGuACCGcAGCCUcAdTsdT antis
    710-729 3961 GAGGCUGCGGUACUUUUUC 3962 GAGGcuGcGGuAcuuuuucdTsdT sense
    710-729 3963 GAAAAAGUACCGCAGCCUC 3964 GAAAAAGuACCGcAGCCUCdTsdT antis
    792-811 3965 ACGGUGUACCGAGUGGCCC 3966 AcGGuGuAccGAGuGGcccdTsdT sense
    792-811 3967 GGGCCACUCGGUACACCGU 3968 GGGCcACUCGGuAcACCGUdTsdT antis
    903-922 3969 CAAGGUGUGUGUCACCGUG 3970 cAAGGuGuGuGucAccGuGdTsdT sense
    903-922 3971 CACGGUGACACACACCUUG 3972 cACGGUGAcAcAcACCUUGdTsdT antis
    1110-1129 3973 GGCUGUGUACUUGCUGAGC 3974 GGcuGuGuAcuuGcuGAGcdTsdT sense
    1110-1129 3975 GCUCAGCAAGUACACAGCC 3976 GCUcAGcAAGuAcAcAGCCdTsdT antis
    1129-1148 3977 UACUUCUCGGCCAGCCCAU 3978 uAcuucucGGccAGcccAudTsdT sense
    1129-1148 3979 AUGGGCUGGCCGAGAAGUA 3980 AUGGGCUGGCCGAGAAGuAdTsdT antis
    1142-1161 3981 GCCCAUCUUCCCUGGGGAC 3982 GcccAucuucccuGGGGAcdTsdT sense
    1142-1161 3983 GUCCCCAGGGAAGAUGGGC 3984 GUCCCcAGGGAAGAUGGGCdTsdT antis
    1153-1172 3985 CUGGGGACAGUGGGGUGGA 3986 cuGGGGAcAGuGGGGuGGAdTsdT sense
    1153-1172 3987 UCCACCCCACUGUCCCCAG 3988 UCcACCCcACUGUCCCcAGdTsdT antis
    1472-1491 3989 UCCUGGUGAACUGUCCAUC 3990 uccuGGuGAAcuGuccAucdTsdT sense
    1472-1491 3991 GAUGGACAGUUCACCAGGA 3992 GAUGGAcAGUUcACcAGGAdTsdT antis
    1473-1492 3993 CCUGGUGAACUGUCCAUCC 3994 ccuGGuGAAcuGuccAuccdTsdT sense
    1473-1492 3995 GGAUGGACAGUUCACCAGG 3996 GGAUGGAcAGUUcACcAGGdTsdT antis
    1652-1671 3997 UAGCUCUUCCUGAGGGCCC 3998 uAGcucuuccuGAGGGcccdTsdT sense
    1652-1671 3999 GGGCCCUCAGGAAGAGCUA 4000 GGGCCCUcAGGAAGAGCuAdTsdT antis
    1653-1672 4001 AGCUCUUCCUGAGGGCCCC 4002 AGcucuuccuGAGGGccccdTsdT sense
    1653-1672 4003 GGGGCCCUCAGGAAGAGCU 4004 GGGGCCCUcAGGAAGAGCUdTsdT antis
    1812-1831 4005 CUCAGCAGCCUAACCUCUG 4006 cucAGcAGccuAAccucuGdTsdT sense
    1812-1831 4007 CAGAGGUUAGGCUGCUGAG 4008 cAGAGGUuAGGCUGCUGAGdTsdT antis
    1952-1971 4009 UCCUUCCCUCCCCCCCUCU 4010 uccuucccucccccccucudTsdT sense
    1952-1971 4011 AGAGGGGGGGAGGGAAGGA 4012 AGAGGGGGGGAGGGAAGGAdTsdT antis
    1968-1987 4013 UCUCCCAGGUCCCUUGUAA 4014 ucucccAGGucccuuGuAAdTsdT sense
    1968-1987 4015 UUACAAGGGACCUGGGAGA 4016 UuAcAAGGGACCUGGGAGAdTsdT antis
    2051-2070 4017 UAUAAUUUUUUCUUAAAGA 4018 uAuAAuuuuuucuuAAAGAdTsdT sense
    2051-2070 4019 UCUUUAAGAAAAAAUUAUA 4020 UCUUuAAGAAAAAAUuAuAdTsdT antis
    2056-2075 4021 UUUUUUCUUAAAGAAAACG 4022 uuuuuucuuAAAGAAAAcGdTsdT sense
    2056-2075 4023 CGUUUUCUUUAAGAAAAAA 4024 CGUUUUCUUuAAGAAAAAAdTsdT antis
    2128-2147 4025 GCUCCCAAGGCUUCCUCCC 4026 GcucccAAGGcuuccucccdTsdT sense
    2128-2147 4027 GGGAGGAAGCCUUGGGAGC 4028 GGGAGGAAGCCUUGGGAGCdTsdT antis
    2135-2154 4029 AGGCUUCCUCCCUCUCCCC 4030 AGGcuuccucccucuccccdTsdT sense
    2135-2154 4031 GGGGAGAGGGAGGAAGCCU 4032 GGGGAGAGGGAGGAAGCCUdTsdT antis
    2136-2155 4033 GGCUUCCUCCCUCUCCCCA 4034 GGcuuccucccucuccccAdTsdT sense
    2136-2155 4035 UGGGGAGAGGGAGGAAGCC 4036 UGGGGAGAGGGAGGAAGCCdTsdT antis
    2147-2166 4037 UCUCCCCAUCCUGGAAGGA 4038 ucuccccAuccuGGAAGGAdTsdT sense
    2147-2166 4039 UCCUUCCAGGAUGGGGAGA 4040 UCCUUCcAGGAUGGGGAGAdTsdT antis
    511-530 4041 UAGGCCAAGGCCCAGAGCG 4042 uAGGccAAGGcccAGAGcGdTsdT sense
    511-530 4043 CGCUCUGGGCCUUGGCCUA 4044 CGCUCUGGGCCUUGGCCuAdTsdT antis
    677-696 4045 GAUUAUGCGUAAGCUGGAC 4046 GAuuAuGcGuAAGcuGGAcdTsdT sense
    677-696 4047 GUCCAGCUUACGCAUAAUC 4048 GUCcAGCUuACGcAuAAUCdTsdT antis
    682-701 4049 UGCGUAAGCUGGACCACUG 4050 uGcGuAAGcuGGAccAcuGdTsdT sense
    682-701 4051 CAGUGGUCCAGCUUACGCA 4052 cAGUGGUCcAGCUuACGcAdTsdT antis
    796-815 4053 UGUACCGAGUGGCCCGCCA 4054 uGuAccGAGuGGcccGccAdTsdT sense
    796-815 4055 UGGCGGGCCACUCGGUACA 4056 UGGCGGGCcACUCGGuAcAdTsdT antis
    750-769 4057 GACGAGCUGUAUUUGAAUC 4058 GAcGAGcuGuAuuuGAAucdTsdT sense
    750-769 4059 GAUUCAAAUACAGCUCGUC 4060 GAUUcAAAuAcAGCUCGUCdTsdT antis
    1646-1665 4061 CCUCGCUAGCUCUUCCUGA 4062 ccucGcuAGcucuuccuGAdTsdT sense
    1646-1665 4063 UCAGGAAGAGCUAGCGAGG 4064 UcAGGAAGAGCuAGCGAGGdTsdT antis
    664-683 4065 ACCGAGAACUGCAGAUUAU 4066 AccGAGAAcuGcAGAuuAudTsdT sense
    664-683 4067 AUAAUCUGCAGUUCUCGGU 4068 AuAAUCUGcAGUUCUCGGUdTsdT antis
    751-770 4069 ACGAGCUGUAUUUGAAUCU 4070 AcGAGcuGuAuuuGAAucudTsdT sense
    751-770 4071 AGAUUCAAAUACAGCUCGU 4072 AGAUUcAAAuAcAGCUCGUdTsdT antis
    835-854 4073 UCACCCCUAUCAUCUACAU 4074 ucAccccuAucAucuAcAudTsdT sense
    835-854 4075 AUGUAGAUGAUAGGGGUGA 4076 AUGuAGAUGAuAGGGGUGAdTsdT antis
    1399-1418 4077 UCUUCGAUGAACUGCGGAG 4078 ucuucGAuGAAcuGcGGAGdTsdT sense
    1399-1418 4079 CUCCGCAGUUCAUCGAAGA 4080 CUCCGcAGUUcAUCGAAGAdTsdT antis
    2175-2194 4081 AGAGAGUCCCUGGUGUCUU 4082 AGAGAGucccuGGuGucuudTsdT sense
    2175-2194 4083 AAGACACCAGGGACUCUCU 4084 AAGAcACcAGGGACUCUCUdTsdT antis
    19-38 4085 ACGGCAGAGGGACUUCAUC 4086 AcGGcAGAGGGAcuucAucdTsdT sense
    19-38 4087 GAUGAAGUCCCUCUGCCGU 4088 GAUGAAGUCCCUCUGCCGUdTsdT antis
    79-98 4089 CCCGAACGGCGCGGCCUGG 4090 cccGAAcGGcGcGGccuGGdTsdT sense
    79-98 4091 CCAGGCCGCGCCGUUCGGG 4092 CcAGGCCGCGCCGUUCGGGdTsdT antis
    186-205 4093 GGCGCCAUGAGCGGCGGCG 4094 GGcGccAuGAGcGGcGGcGdTsdT sense
    186-205 4095 CGCCGCCGCUCAUGGCGCC 4096 CGCCGCCGCUcAUGGCGCCdTsdT antis
    187-206 4097 GCGCCAUGAGCGGCGGCGG 4098 GcGccAuGAGcGGcGGcGGdTsdT sense
    187-206 4099 CCGCCGCCGCUCAUGGCGC 4100 CCGCCGCCGCUcAUGGCGCdTsdT antis
    334-353 4101 GCGGGAAAGCGUCAGUCGG 4102 GcGGGAAAGcGucAGucGGdTsdT sense
    334-353 4103 CCGACUGACGCUUUCCCGC 4104 CCGACUGACGCUUUCCCGCdTsdT antis
    349-368 4105 UCGGGGCUAUGGGUGGGGG 4106 ucGGGGcuAuGGGuGGGGGdTsdT sense
    349-368 4107 CCCCCACCCAUAGCCCCGA 4108 CCCCcACCcAuAGCCCCGAdTsdT antis
    451-470 4109 CGCCGCCGGGAGUGAAGCU 4110 cGccGccGGGAGuGAAGcudTsdT sense
    451-470 4111 AGCUUCACUCCCGGCGGCG 4112 AGCUUcACUCCCGGCGGCGdTsdT antis
    476-495 4113 UGACAGCGGGAAGGUGACC 4114 uGAcAGcGGGAAGGuGAccdTsdT sense
    476-495 4115 GGUCACCUUCCCGCUGUCA 4116 GGUcACCUUCCCGCUGUcAdTsdT antis
    480-499 4117 AGCGGGAAGGUGACCACAG 4118 AGcGGGAAGGuGAccAcAGdTsdT sense
    480-499 4119 CUGUGGUCACCUUCCCGCU 4120 CUGUGGUcACCUUCCCGCUdTsdT antis
    481-500 4121 GCGGGAAGGUGACCACAGU 4122 GcGGGAAGGuGAccAcAGudTsdT sense
    481-500 4123 ACUGUGGUCACCUUCCCGC 4124 ACUGUGGUcACCUUCCCGCdTsdT antis
    516-535 4125 CAAGGCCCAGAGCGUUCCC 4126 cAAGGcccAGAGcGuucccdTsdT sense
    516-535 4127 GGGAACGCUCUGGGCCUUG 4128 GGGAACGCUCUGGGCCUUGdTsdT antis
    586-605 4129 UAGUAUACCAGGCACGGCU 4130 uAGuAuAccAGGcAcGGcudTsdT sense
    586-605 4131 AGCCGUGCCUGGUAUACUA 4132 AGCCGUGCCUGGuAuACuAdTsdT antis
    608-627 4133 AGAGACGAGGGAACUGGUG 4134 AGAGAcGAGGGAAcuGGuGdTsdT sense
    608-627 4135 CACCAGUUCCCUCGUCUCU 4136 cACcAGUUCCCUCGUCUCUdTsdT antis
    662-681 4137 GAACCGAGAACUGCAGAUU 4138 GAAccGAGAAcuGcAGAuudTsdT sense
    662-681 4139 AAUCUGCAGUUCUCGGUUC 4140 AAUCUGcAGUUCUCGGUUCdTsdT antis
    678-697 4141 AUUAUGCGUAAGCUGGACC 4142 AuuAuGcGuAAGcuGGAccdTsdT sense
    678-697 4143 GGUCCAGCUUACGCAUAAU 4144 GGUCcAGCUuACGcAuAAUdTsdT antis
    679-698 4145 UUAUGCGUAAGCUGGACCA 4146 uuAuGcGuAAGcuGGAccAdTsdT sense
    679-698 4147 UGGUCCAGCUUACGCAUAA 4148 UGGUCcAGCUuACGcAuAAdTsdT antis
    680-699 4149 UAUGCGUAAGCUGGACCAC 4150 uAuGcGuAAGcuGGAccAcdTsdT sense
    680-699 4151 GUGGUCCAGCUUACGCAUA 4152 GUGGUCcAGCUuACGcAuAdTsdT antis
    683-702 4153 GCGUAAGCUGGACCACUGC 4154 GcGuAAGcuGGAccAcuGcdTsdT sense
    683-702 4155 GCAGUGGUCCAGCUUACGC 4156 GcAGUGGUCcAGCUuACGCdTsdT antis
    714-733 4157 CUGCGGUACUUUUUCUACU 4158 cuGcGGuAcuuuuucuAcudTsdT sense
    714-733 4159 AGUAGAAAAAGUACCGCAG 4160 AGuAGAAAAAGuACCGcAGdTsdT antis
    715-734 4161 UGCGGUACUUUUUCUACUC 4162 uGcGGuAcuuuuucuAcucdTsdT sense
    715-734 4163 GAGUAGAAAAAGUACCGCA 4164 GAGuAGAAAAAGuACCGcAdTsdT antis
    754-773 4165 AGCUGUAUUUGAAUCUGGU 4166 AGcuGuAuuuGAAucuGGudTsdT sense
    754-773 4167 ACCAGAUUCAAAUACAGCU 4168 ACcAGAUUcAAAuAcAGCUdTsdT antis
    795-814 4169 GUGUACCGAGUGGCCCGCC 4170 GuGuAccGAGuGGcccGccdTsdT sense
    795-814 4171 GGCGGGCCACUCGGUACAC 4172 GGCGGGCcACUCGGuAcACdTsdT antis
    797-816 4173 GUACCGAGUGGCCCGCCAC 4174 GuAccGAGuGGcccGccAcdTsdT sense
    797-816 4175 GUGGCGGGCCACUCGGUAC 4176 GUGGCGGGCcACUCGGuACdTsdT antis
    799-818 4177 ACCGAGUGGCCCGCCACUU 4178 AccGAGuGGcccGccAcuudTsdT sense
    799-818 4179 AAGUGGCGGGCCACUCGGU 4180 AAGUGGCGGGCcACUCGGUdTsdT antis
    800-819 4181 CCGAGUGGCCCGCCACUUC 4182 ccGAGuGGcccGccAcuucdTsdT sense
    800-819 4183 GAAGUGGCGGGCCACUCGG 4184 GAAGUGGCGGGCcACUCGGdTsdT antis
    834-853 4185 AUCACCCCUAUCAUCUACA 4186 AucAccccuAucAucuAcAdTsdT sense
    834-853 4187 UGUAGAUGAUAGGGGUGAU 4188 UGuAGAUGAuAGGGGUGAUdTsdT antis
    845-864 4189 CAUCUACAUCAAGGUGUAC 4190 cAucuAcAucAAGGuGuAcdTsdT sense
    845-864 4191 GUACACCUUGAUGUAGAUG 4192 GuAcACCUUGAUGuAGAUGdTsdT antis
    850-869 4193 ACAUCAAGGUGUACAUGUA 4194 AcAucAAGGuGuAcAuGuAdTsdT sense
    850-869 4195 UACAUGUACACCUUGAUGU 4196 uAcAUGuAcACCUUGAUGUdTsdT antis
    885-904 4197 UUGGCCUACAUCCACUCCC 4198 uuGGccuAcAuccAcucccdTsdT sense
    885-904 4199 GGGAGUGGAUGUAGGCCAA 4200 GGGAGUGGAUGuAGGCcAAdTsdT antis
    890-909 4201 CUACAUCCACUCCCAAGGU 4202 cuAcAuccAcucccAAGGudTsdT sense
    890-909 4203 ACCUUGGGAGUGGAUGUAG 4204 ACCUUGGGAGUGGAUGuAGdTsdT antis
    921-940 4205 GACAUCAAGCCCCAGAAUU 4206 GAcAucAAGccccAGAAuudTsdT sense
    921-940 4207 AAUUCUGGGGCUUGAUGUC 4208 AAUUCUGGGGCUUGAUGUCdTsdT antis
    934-953 4209 AGAAUUUGCUUGUGGACCC 4210 AGAAuuuGcuuGuGGAcccdTsdT sense
    934-953 4211 GGGUCCACAAGCAAAUUCU 4212 GGGUCcAcAAGcAAAUUCUdTsdT antis
    1032-1051 4213 UGCUCUCGGUACUACCGUG 4214 uGcucucGGuAcuAccGuGdTsdT sense
    1032-1051 4215 CACGGUAGUACCGAGAGCA 4216 cACGGuAGuACCGAGAGcAdTsdT antis
    1033-1052 4217 GCUCUCGGUACUACCGUGC 4218 GcucucGGuAcuAccGuGcdTsdT sense
    1033-1052 4219 GCACGGUAGUACCGAGAGC 4220 GcACGGuAGuACCGAGAGCdTsdT antis
    1081-1100 4221 ACACCUCGUCCAUCGAUGU 4222 AcAccucGuccAucGAuGudTsdT sense
    1081-1100 4223 ACAUCGAUGGACGAGGUGU 4224 AcAUCGAUGGACGAGGUGUdTsdT antis
    1082-1101 4225 CACCUCGUCCAUCGAUGUG 4226 cAccucGuccAucGAuGuGdTsdT sense
    1082-1101 4227 CACAUCGAUGGACGAGGUG 4228 cAcAUCGAUGGACGAGGUGdTsdT antis
    1083-1102 4229 ACCUCGUCCAUCGAUGUGU 4230 AccucGuccAucGAuGuGudTsdT sense
    1083-1102 4231 ACACAUCGAUGGACGAGGU 4232 AcAcAUCGAUGGACGAGGUdTsdT antis
    1241-1260 4233 CUAUACGGAGUUCAAGUUC 4234 cuAuAcGGAGuucAAGuucdTsdT sense
    1241-1260 4235 GAACUUGAACUCCGUAUAG 4236 GAACUUGAACUCCGuAuAGdTsdT antis
    1242-1261 4237 UAUACGGAGUUCAAGUUCC 4238 uAuAcGGAGuucAAGuuccdTsdT sense
    1242-1261 4239 GGAACUUGAACUCCGUAUA 4240 GGAACUUGAACUCCGuAuAdTsdT antis
    1243-1262 4241 AUACGGAGUUCAAGUUCCC 4242 AuAcGGAGuucAAGuucccdTsdT sense
    1243-1262 4243 GGGAACUUGAACUCCGUAU 4244 GGGAACUUGAACUCCGuAUdTsdT antis
    1396-1415 4245 GCUUCUUCGAUGAACUGCG 4246 GcuucuucGAuGAAcuGcGdTsdT sense
    1396-1415 4247 CGCAGUUCAUCGAAGAAGC 4248 CGcAGUUcAUCGAAGAAGCdTsdT antis
    1397-1416 4249 CUUCUUCGAUGAACUGCGG 4250 cuucuucGAuGAAcuGcGGdTsdT sense
    1397-1416 4251 CCGCAGUUCAUCGAAGAAG 4252 CCGcAGUUcAUCGAAGAAGdTsdT antis
    1398-1417 4253 UUCUUCGAUGAACUGCGGA 4254 uucuucGAuGAAcuGcGGAdTsdT sense
    1398-1417 4255 UCCGCAGUUCAUCGAAGAA 4256 UCCGcAGUUcAUCGAAGAAdTsdT antis
    1400-1419 4257 CUUCGAUGAACUGCGGAGA 4258 cuucGAuGAAcuGcGGAGAdTsdT sense
    1400-1419 4259 UCUCCGCAGUUCAUCGAAG 4260 UCUCCGcAGUUcAUCGAAGdTsdT antis
    1452-1471 4261 CCCCCCCUGUUCAACUUCA 4262 cccccccuGuucAAcuucAdTsdT sense
    1452-1471 4263 UGAAGUUGAACAGGGGGGG 4264 UGAAGUUGAAcAGGGGGGGdTsdT antis
    1576-1595 4265 CAUCCUCACAAGCUUUAAC 4266 cAuccucAcAAGcuuuAAcdTsdT sense
    1576-1595 4267 GUUAAAGCUUGUGAGGAUG 4268 GUuAAAGCUUGUGAGGAUGdTsdT antis
    1634-1653 4269 CACAACUGCUACCCUCGCU 4270 cAcAAcuGcuAcccucGcudTsdT sense
    1634-1653 4271 AGCGAGGGUAGCAGUUGUG 4272 AGCGAGGGuAGcAGUUGUGdTsdT antis
    1635-1654 4273 ACAACUGCUACCCUCGCUA 4274 AcAAcuGcuAcccucGcuAdTsdT sense
    1635-1654 4275 UAGCGAGGGUAGCAGUUGU 4276 uAGCGAGGGuAGcAGUUGUdTsdT antis
    1643-1662 4277 UACCCUCGCUAGCUCUUCC 4278 uAcccucGcuAGcucuuccdTsdT sense
    1643-1662 4279 GGAAGAGCUAGCGAGGGUA 4280 GGAAGAGCuAGCGAGGGuAdTsdT antis
    1645-1664 4281 CCCUCGCUAGCUCUUCCUG 4282 cccucGcuAGcucuuccuGdTsdT sense
    1645-1664 4283 CAGGAAGAGCUAGCGAGGG 4284 cAGGAAGAGCuAGCGAGGGdTsdT antis
    1660-1679 4285 CCUGAGGGCCCCACCGACU 4286 ccuGAGGGccccAccGAcudTsdT sense
    1660-1679 4287 AGUCGGUGGGGCCCUCAGG 4288 AGUCGGUGGGGCCCUcAGGdTsdT antis
    1664-1683 4289 AGGGCCCCACCGACUACCC 4290 AGGGccccAccGAcuAcccdTsdT sense
    1664-1683 4291 GGGUAGUCGGUGGGGCCCU 4292 GGGuAGUCGGUGGGGCCCUdTsdT antis
    1665-1684 4293 GGGCCCCACCGACUACCCC 4294 GGGccccAccGAcuAccccdTsdT sense
    1665-1684 4295 GGGGUAGUCGGUGGGGCCC 4296 GGGGuAGUCGGUGGGGCCCdTsdT antis
    1816-1835 4297 GCAGCCUAACCUCUGUGGU 4298 GcAGccuAAccucuGuGGudTsdT sense
    1816-1835 4299 ACCACAGAGGUUAGGCUGC 4300 ACcAcAGAGGUuAGGCUGCdTsdT antis
    1817-1836 4301 CAGCCUAACCUCUGUGGUG 4302 cAGccuAAccucuGuGGuGdTsdT sense
    1817-1836 4303 CACCACAGAGGUUAGGCUG 4304 cACcAcAGAGGUuAGGCUGdTsdT antis
    1973-1992 4305 CAGGUCCCUUGUAAAUAGA 4306 cAGGucccuuGuAAAuAGAdTsdT sense
    1973-1992 4307 UCUAUUUACAAGGGACCUG 4308 UCuAUUuAcAAGGGACCUGdTsdT antis
    2206-2225 4309 AAGGUUUGCCUGUGUACAG 4310 AAGGuuuGccuGuGuAcAGdTsdT sense
    2206-2225 4311 CUGUACACAGGCAAACCUU 4312 CUGuAcAcAGGcAAACCUUdTsdT antis
    2207-2226 4313 AGGUUUGCCUGUGUACAGA 4314 AGGuuuGccuGuGuAcAGAdTsdT sense
    2207-2226 4315 UCUGUACACAGGCAAACCU 4316 UCUGuAcAcAGGcAAACCUdTsdT antis
    2222-2241 4317 CAGACCUCUGUUCAAUAAA 4318 cAGAccucuGuucAAuAAAdTsdT sense
    2222-2241 4319 UUUAUUGAACAGAGGUCUG 4320 UUuAUUGAAcAGAGGUCUGdTsdT antis
    542-561 4321 GGCUUACACUGACAUCAAA 4322 GGcuuAcAcuGAcAucAAAdTsdT sense
    542-561 4323 UUUGAUGUCAGUGUAAGCC 4324 UUUGAUGUcAGUGuAAGCCdTsdT antis
    681-700 4325 AUGCGUAAGCUGGACCACU 4326 AuGcGuAAGcuGGAccAcudTsdT sense
    681-700 4327 AGUGGUCCAGCUUACGCAU 4328 AGUGGUCcAGCUuACGcAUdTsdT antis
    748-767 4329 AGGACGAGCUGUAUUUGAA 4330 AGGAcGAGcuGuAuuuGAAdTsdT sense
    748-767 4331 UUCAAAUACAGCUCGUCCU 4332 UUcAAAuAcAGCUCGUCCUdTsdT antis
    749-768 4333 GGACGAGCUGUAUUUGAAU 4334 GGAcGAGcuGuAuuuGAAudTsdT sense
    749-768 4335 AUUCAAAUACAGCUCGUCC 4336 AUUcAAAuAcAGCUCGUCCdTsdT antis
    1352-1371 4337 CACGCCAUCCUCAAGGCUC 4338 cAcGccAuccucAAGGcucdTsdT sense
    1352-1371 4339 GAGCCUUGAGGAUGGCGUG 4340 GAGCCUUGAGGAUGGCGUGdTsdT antis
    1944-1963 4341 GCUACCACUCCUUCCCUCC 4342 GcuAccAcuccuucccuccdTsdT sense
    1944-1963 4343 GGAGGGAAGGAGUGGUAGC 4344 GGAGGGAAGGAGUGGuAGCdTsdT antis
    2004-2023 4345 CAUCUCUCGUCUUCCCUUC 4346 cAucucucGucuucccuucdTsdT sense
    2004-2023 4347 GAAGGGAAGACGAGAGAUG 4348 GAAGGGAAGACGAGAGAUGdTsdT antis
    348-367 4349 GUCGGGGCUAUGGGUGGGG 4350 GucGGGGcuAuGGGuGGGGdTsdT sense
    348-367 4351 CCCCACCCAUAGCCCCGAC 4352 CCCcACCcAuAGCCCCGACdTsdT antis
    39-58 4353 CCCGGCGUGCCCCGCGGCG 4354 cccGGcGuGccccGcGGcGdTsdT sense
    39-58 4355 CGCCGCGGGGCACGCCGGG 4356 CGCCGCGGGGcACGCCGGGdTsdT antis
    184-203 4357 UCGGCGCCAUGAGCGGCGG 4358 ucGGcGccAuGAGcGGcGGdTsdT sense
    184-203 4359 CCGCCGCUCAUGGCGCCGA 4360 CCGCCGCUcAUGGCGCCGAdTsdT antis
    344-363 4361 GUCAGUCGGGGCUAUGGGU 4362 GucAGucGGGGcuAuGGGudTsdT sense
    344-363 4363 ACCCAUAGCCCCGACUGAC 4364 ACCcAuAGCCCCGACUGACdTsdT antis
    347-366 4365 AGUCGGGGCUAUGGGUGGG 4366 AGucGGGGcuAuGGGuGGGdTsdT sense
    347-366 4367 CCCACCCAUAGCCCCGACU 4368 CCcACCcAuAGCCCCGACUdTsdT antis
    454-473 4369 CGCCGGGAGUGAAGCUGGG 4370 cGccGGGAGuGAAGcuGGGdTsdT sense
    454-473 4371 CCCAGCUUCACUCCCGGCG 4372 CCcAGCUUcACUCCCGGCGdTsdT antis
    456-475 4373 CCGGGAGUGAAGCUGGGCC 4374 ccGGGAGuGAAGcuGGGccdTsdT sense
    456-475 4375 GGCCCAGCUUCACUCCCGG 4376 GGCCcAGCUUcACUCCCGGdTsdT antis
    477-496 4377 GACAGCGGGAAGGUGACCA 4378 GAcAGcGGGAAGGuGAccAdTsdT sense
    477-496 4379 UGGUCACCUUCCCGCUGUC 4380 UGGUcACCUUCCCGCUGUCdTsdT antis
    479-498 4381 CAGCGGGAAGGUGACCACA 4382 cAGcGGGAAGGuGAccAcAdTsdT sense
    479-498 4383 UGUGGUCACCUUCCCGCUG 4384 UGUGGUcACCUUCCCGCUGdTsdT antis
    517-536 4385 AAGGCCCAGAGCGUUCCCA 4386 AAGGcccAGAGcGuucccAdTsdT sense
    517-536 4387 UGGGAACGCUCUGGGCCUU 4388 UGGGAACGCUCUGGGCCUUdTsdT antis
    518-537 4389 AGGCCCAGAGCGUUCCCAA 4390 AGGcccAGAGcGuucccAAdTsdT sense
    518-537 4391 UUGGGAACGCUCUGGGCCU 4392 UUGGGAACGCUCUGGGCCUdTsdT antis
    519-538 4393 GGCCCAGAGCGUUCCCAAG 4394 GGcccAGAGcGuucccAAGdTsdT sense
    519-538 4395 CUUGGGAACGCUCUGGGCC 4396 CUUGGGAACGCUCUGGGCCdTsdT antis
    544-563 4397 CUUACACUGACAUCAAAGU 4398 cuuAcAcuGAcAucAAAGudTsdT sense
    544-563 4399 ACUUUGAUGUCAGUGUAAG 4400 ACUUUGAUGUcAGUGuAAGdTsdT antis
    545-564 4401 UUACACUGACAUCAAAGUG 4402 uuAcAcuGAcAucAAAGuGdTsdT sense
    545-564 4403 CACUUUGAUGUCAGUGUAA 4404 cACUUUGAUGUcAGUGuAAdTsdT antis
    603-622 4405 CUGGCAGAGACGAGGGAAC 4406 cuGGcAGAGAcGAGGGAAcdTsdT sense
    603-622 4407 GUUCCCUCGUCUCUGCCAG 4408 GUUCCCUCGUCUCUGCcAGdTsdT antis
    604-623 4409 UGGCAGAGACGAGGGAACU 4410 uGGcAGAGAcGAGGGAAcudTsdT sense
    604-623 4411 AGUUCCCUCGUCUCUGCCA 4412 AGUUCCCUCGUCUCUGCcAdTsdT antis
    741-760 4413 GAGAAGAAGGACGAGCUGU 4414 GAGAAGAAGGAcGAGcuGudTsdT sense
    741-760 4415 ACAGCUCGUCCUUCUUCUC 4416 AcAGCUCGUCCUUCUUCUCdTsdT antis
    752-771 4417 CGAGCUGUAUUUGAAUCUG 4418 cGAGcuGuAuuuGAAucuGdTsdT sense
    752-771 4419 CAGAUUCAAAUACAGCUCG 4420 cAGAUUcAAAuAcAGCUCGdTsdT antis
    753-772 4421 GAGCUGUAUUUGAAUCUGG 4422 GAGcuGuAuuuGAAucuGGdTsdT sense
    753-772 4423 CCAGAUUCAAAUACAGCUC 4424 CcAGAUUcAAAuAcAGCUCdTsdT antis
    831-850 4425 CUGAUCACCCCUAUCAUCU 4426 cuGAucAccccuAucAucudTsdT sense
    831-850 4427 AGAUGAUAGGGGUGAUCAG 4428 AGAUGAuAGGGGUGAUcAGdTsdT antis
    832-851 4429 UGAUCACCCCUAUCAUCUA 4430 uGAucAccccuAucAucuAdTsdT sense
    832-851 4431 UAGAUGAUAGGGGUGAUCA 4432 uAGAUGAuAGGGGUGAUcAdTsdT antis
    833-852 4433 GAUCACCCCUAUCAUCUAC 4434 GAucAccccuAucAucuAcdTsdT sense
    833-852 4435 GUAGAUGAUAGGGGUGAUC 4436 GuAGAUGAuAGGGGUGAUCdTsdT antis
    913-932 4437 GUCACCGUGACAUCAAGCC 4438 GucAccGuGAcAucAAGccdTsdT sense
    913-932 4439 GGCUUGAUGUCACGGUGAC 4440 GGCUUGAUGUcACGGUGACdTsdT antis
    918-937 4441 CGUGACAUCAAGCCCCAGA 4442 cGuGAcAucAAGccccAGAdTsdT sense
    918-937 4443 UCUGGGGCUUGAUGUCACG 4444 UCUGGGGCUUGAUGUcACGdTsdT antis
    920-939 4445 UGACAUCAAGCCCCAGAAU 4446 uGAcAucAAGccccAGAAudTsdT sense
    920-939 4447 AUUCUGGGGCUUGAUGUCA 4448 AUUCUGGGGCUUGAUGUcAdTsdT antis
    1018-1037 4449 AUGUGUCCUACAUCUGCUC 4450 AuGuGuccuAcAucuGcucdTsdT sense
    1018-1037 4451 GAGCAGAUGUAGGACACAU 4452 GAGcAGAUGuAGGAcAcAUdTsdT antis
    1019-1038 4453 UGUGUCCUACAUCUGCUCU 4454 uGuGuccuAcAucuGcucudTsdT sense
    1019-1038 4455 AGAGCAGAUGUAGGACACA 4456 AGAGcAGAUGuAGGAcAcAdTsdT antis
    1097-1116 4457 UGUGUGGUCGGCUGGCUGU 4458 uGuGuGGucGGcuGGcuGudTsdT sense
    1097-1116 4459 ACAGCCAGCCGACCACACA 4460 AcAGCcAGCCGACcAcAcAdTsdT antis
    1102-1121 4461 GGUCGGCUGGCUGUGUACU 4462 GGucGGcuGGcuGuGuAcudTsdT sense
    1102-1121 4463 AGUACACAGCCAGCCGACC 4464 AGuAcAcAGCcAGCCGACCdTsdT antis
    1155-1174 4465 GGGGACAGUGGGGUGGACC 4466 GGGGAcAGuGGGGuGGAccdTsdT sense
    1155-1174 4467 GGUCCACCCCACUGUCCCC 4468 GGUCcACCCcACUGUCCCCdTsdT antis
    1245-1264 4469 ACGGAGUUCAAGUUCCCCC 4470 AcGGAGuucAAGuucccccdTsdT sense
    1245-1264 4471 GGGGGAACUUGAACUCCGU 4472 GGGGGAACUUGAACUCCGUdTsdT antis
    1274-1293 4473 UCACCCUUGGACAAAGGUG 4474 ucAcccuuGGAcAAAGGuGdTsdT sense
    1274-1293 4475 CACCUUUGUCCAAGGGUGA 4476 cACCUUUGUCcAAGGGUGAdTsdT antis
    1276-1295 4477 ACCCUUGGACAAAGGUGUU 4478 AcccuuGGAcAAAGGuGuudTsdT sense
    1276-1295 4479 AACACCUUUGUCCAAGGGU 4480 AAcACCUUUGUCcAAGGGUdTsdT antis
    1316-1335 4481 UGAGGCCAUUGCACUCUGC 4482 uGAGGccAuuGcAcucuGcdTsdT sense
    1316-1335 4483 GCAGAGUGCAAUGGCCUCA 4484 GcAGAGUGcAAUGGCCUcAdTsdT antis
    1318-1337 4485 AGGCCAUUGCACUCUGCUC 4486 AGGccAuuGcAcucuGcucdTsdT sense
    1318-1337 4487 GAGCAGAGUGCAAUGGCCU 4488 GAGcAGAGUGcAAUGGCCUdTsdT antis
    1321-1340 4489 CCAUUGCACUCUGCUCUAG 4490 ccAuuGcAcucuGcucuAGdTsdT sense
    1321-1340 4491 CUAGAGCAGAGUGCAAUGG 4492 CuAGAGcAGAGUGcAAUGGdTsdT antis
    1325-1344 4493 UGCACUCUGCUCUAGCCUA 4494 uGcAcucuGcucuAGccuAdTsdT sense
    1325-1344 4495 UAGGCUAGAGCAGAGUGCA 4496 uAGGCuAGAGcAGAGUGcAdTsdT antis
    1337-1356 4497 UAGCCUACUGGAGUACACG 4498 uAGccuAcuGGAGuAcAcGdTsdT sense
    1337-1356 4499 CGUGUACUCCAGUAGGCUA 4500 CGUGuACUCcAGuAGGCuAdTsdT antis
    1375-1394 4501 CACUCGAGGCUUGUGCCCA 4502 cAcucGAGGcuuGuGcccAdTsdT sense
    1375-1394 4503 UGGGCACAAGCCUCGAGUG 4504 UGGGcAcAAGCCUCGAGUGdTsdT antis
    1443-1462 4505 CGCCCGCUUCCCCCCCUGU 4506 cGcccGcuucccccccuGudTsdT sense
    1443-1462 4507 ACAGGGGGGGAAGCGGGCG 4508 AcAGGGGGGGAAGCGGGCGdTsdT antis
    1466-1485 4509 CUUCAGUCCUGGUGAACUG 4510 cuucAGuccuGGuGAAcuGdTsdT sense
    1466-1485 4511 CAGUUCACCAGGACUGAAG 4512 cAGUUcACcAGGACUGAAGdTsdT antis
    1581-1600 4513 UCACAAGCUUUAACUGAAG 4514 ucAcAAGcuuuAAcuGAAGdTsdT sense
    1581-1600 4515 CUUCAGUUAAAGCUUGUGA 4516 CUUcAGUuAAAGCUUGUGAdTsdT antis
    1602-1621 4517 CAGACUGGCCAAGAUUGGC 4518 cAGAcuGGccAAGAuuGGcdTsdT sense
    1602-1621 4519 GCCAAUCUUGGCCAGUCUG 4520 GCcAAUCUUGGCcAGUCUGdTsdT antis
    1603-1622 4521 AGACUGGCCAAGAUUGGCA 4522 AGAcuGGccAAGAuuGGcAdTsdT sense
    1603-1622 4523 UGCCAAUCUUGGCCAGUCU 4524 UGCcAAUCUUGGCcAGUCUdTsdT antis
    1644-1663 4525 ACCCUCGCUAGCUCUUCCU 4526 AcccucGcuAGcucuuccudTsdT sense
    1644-1663 4527 AGGAAGAGCUAGCGAGGGU 4528 AGGAAGAGCuAGCGAGGGUdTsdT antis
    1666-1685 4529 GGCCCCACCGACUACCCCU 4530 GGccccAccGAcuAccccudTsdT sense
    1666-1685 4531 AGGGGUAGUCGGUGGGGCC 4532 AGGGGuAGUCGGUGGGGCCdTsdT antis
    1820-1839 4533 CCUAACCUCUGUGGUGGGC 4534 ccuAAccucuGuGGuGGGcdTsdT sense
    1820-1839 4535 GCCCACCACAGAGGUUAGG 4536 GCCcACcAcAGAGGUuAGGdTsdT antis
    1821-1840 4537 CUAACCUCUGUGGUGGGCU 4538 cuAAccucuGuGGuGGGcudTsdT sense
    1821-1840 4539 AGCCCACCACAGAGGUUAG 4540 AGCCcACcAcAGAGGUuAGdTsdT antis
    1855-1874 4541 UAACUGUUUGUAGGGGAGG 4542 uAAcuGuuuGuAGGGGAGGdTsdT sense
    1855-1874 4543 CCUCCCCUACAAACAGUUA 4544 CCUCCCCuAcAAAcAGUuAdTsdT antis
    1861-1880 4545 UUUGUAGGGGAGGGGAGAA 4546 uuuGuAGGGGAGGGGAGAAdTsdT sense
    1861-1880 4547 UUCUCCCCUCCCCUACAAA 4548 UUCUCCCCUCCCCuAcAAAdTsdT antis
    1912-1931 4549 UUCUACCCCCUUGGUCCCC 4550 uucuAcccccuuGGuccccdTsdT sense
    1912-1931 4551 GGGGACCAAGGGGGUAGAA 4552 GGGGACcAAGGGGGuAGAAdTsdT antis
    1960-1979 4553 UCCCCCCCUCUCCCAGGUC 4554 ucccccccucucccAGGucdTsdT sense
    1960-1979 4555 GACCUGGGAGAGGGGGGGA 4556 GACCUGGGAGAGGGGGGGAdTsdT antis
    2009-2028 4557 CUCGUCUUCCCUUCCCUGG 4558 cucGucuucccuucccuGGdTsdT sense
    2009-2028 4559 CCAGGGAAGGGAAGACGAG 4560 CcAGGGAAGGGAAGACGAGdTsdT antis
    2010-2029 4561 UCGUCUUCCCUUCCCUGGC 4562 ucGucuucccuucccuGGcdTsdT sense
    2010-2029 4563 GCCAGGGAAGGGAAGACGA 4564 GCcAGGGAAGGGAAGACGAdTsdT antis
    2011-2030 4565 CGUCUUCCCUUCCCUGGCC 4566 cGucuucccuucccuGGccdTsdT sense
    2011-2030 4567 GGCCAGGGAAGGGAAGACG 4568 GGCcAGGGAAGGGAAGACGdTsdT antis
    2223-2242 4569 AGACCUCUGUUCAAUAAAU 4570 AGAccucuGuucAAuAAAudTsdT sense
    2223-2242 4571 AUUUAUUGAACAGAGGUCU 4572 AUUuAUUGAAcAGAGGUCUdTsdT antis
    2226-2245 4573 CCUCUGUUCAAUAAAUUAU 4574 ccucuGuucAAuAAAuuAudTsdT sense
    2226-2245 4575 AUAAUUUAUUGAACAGAGG 4576 AuAAUUuAUUGAAcAGAGGdTsdT antis
    2228-2247 4577 UCUGUUCAAUAAAUUAUUG 4578 ucuGuucAAuAAAuuAuuGdTsdT sense
    2228-2247 4579 CAAUAAUUUAUUGAACAGA 4580 cAAuAAUUuAUUGAAcAGAdTsdT antis
     9-28 4581 AACGAAGCCGACGGCAGAG 4582 AAcGAAGccGAcGGcAGAGdTsdT sense
     9-28 4583 CUCUGCCGUCGGCUUCGUU 4584 CUCUGCCGUCGGCUUCGUUdTsdT antis
    10-29 4585 ACGAAGCCGACGGCAGAGG 4586 AcGAAGccGAcGGcAGAGGdTsdT sense
    10-29 4587 CCUCUGCCGUCGGCUUCGU 4588 CCUCUGCCGUCGGCUUCGUdTsdT antis
    20-39 4589 CGGCAGAGGGACUUCAUCU 4590 cGGcAGAGGGAcuucAucudTsdT sense
    20-39 4591 AGAUGAAGUCCCUCUGCCG 4592 AGAUGAAGUCCCUCUGCCGdTsdT antis
    26-45 4593 AGGGACUUCAUCUCCCGGC 4594 AGGGAcuucAucucccGGcdTsdT sense
    26-45 4595 GCCGGGAGAUGAAGUCCCU 4596 GCCGGGAGAUGAAGUCCCUdTsdT antis
    27-46 4597 GGGACUUCAUCUCCCGGCG 4598 GGGAcuucAucucccGGcGdTsdT sense
    27-46 4599 CGCCGGGAGAUGAAGUCCC 4600 CGCCGGGAGAUGAAGUCCCdTsdT antis
    28-47 4601 GGACUUCAUCUCCCGGCGU 4602 GGAcuucAucucccGGcGudTsdT sense
    28-47 4603 ACGCCGGGAGAUGAAGUCC 4604 ACGCCGGGAGAUGAAGUCCdTsdT antis
    29-48 4605 GACUUCAUCUCCCGGCGUG 4606 GAcuucAucucccGGcGuGdTsdT sense
    29-48 4607 CACGCCGGGAGAUGAAGUC 4608 cACGCCGGGAGAUGAAGUCdTsdT antis
    37-56 4609 CUCCCGGCGUGCCCCGCGG 4610 cucccGGcGuGccccGcGGdTsdT sense
    37-56 4611 CCGCGGGGCACGCCGGGAG 4612 CCGCGGGGcACGCCGGGAGdTsdT antis
    38-57 4613 UCCCGGCGUGCCCCGCGGC 4614 ucccGGcGuGccccGcGGcdTsdT sense
    38-57 4615 GCCGCGGGGCACGCCGGGA 4616 GCCGCGGGGcACGCCGGGAdTsdT antis
    42-61 4617 GGCGUGCCCCGCGGCGGGC 4618 GGcGuGccccGcGGcGGGcdTsdT sense
    42-61 4619 GCCCGCCGCGGGGCACGCC 4620 GCCCGCCGCGGGGcACGCCdTsdT antis
    43-62 4621 GCGUGCCCCGCGGCGGGCG 4622 GcGuGccccGcGGcGGGcGdTsdT sense
    43-62 4623 CGCCCGCCGCGGGGCACGC 4624 CGCCCGCCGCGGGGcACGCdTsdT antis
    59-78 4625 GCGCUGGGCCGGAGCCGGA 4626 GcGcuGGGccGGAGccGGAdTsdT sense
    59-78 4627 UCCGGCUCCGGCCCAGCGC 4628 UCCGGCUCCGGCCcAGCGCdTsdT antis
    60-79 4629 CGCUGGGCCGGAGCCGGAG 4630 cGcuGGGccGGAGccGGAGdTsdT sense
    60-79 4631 CUCCGGCUCCGGCCCAGCG 4632 CUCCGGCUCCGGCCcAGCGdTsdT antis
     99-118 4633 AGAGGCCGGAGCCCAGGGG 4634 AGAGGccGGAGcccAGGGGdTsdT sense
     99-118 4635 CCCCUGGGCUCCGGCCUCU 4636 CCCCUGGGCUCCGGCCUCUdTsdT antis
    108-127 4637 AGCCCAGGGGAGGCGGCGG 4638 AGcccAGGGGAGGcGGcGGdTsdT sense
    108-127 4639 CCGCCGCCUCCCCUGGGCU 4640 CCGCCGCCUCCCCUGGGCUdTsdT antis
    109-128 4641 GCCCAGGGGAGGCGGCGGC 4642 GcccAGGGGAGGcGGcGGcdTsdT sense
    109-128 4643 GCCGCCGCCUCCCCUGGGC 4644 GCCGCCGCCUCCCCUGGGCdTsdT antis
    133-152 4645 CAGCGGCGGGGGCAGCCCA 4646 cAGcGGcGGGGGcAGcccAdTsdT sense
    133-152 4647 UGGGCUGCCCCCGCCGCUG 4648 UGGGCUGCCCCCGCCGCUGdTsdT antis
    135-154 4649 GCGGCGGGGGCAGCCCAGG 4650 GcGGcGGGGGcAGcccAGGdTsdT sense
    135-154 4651 CCUGGGCUGCCCCCGCCGC 4652 CCUGGGCUGCCCCCGCCGCdTsdT antis
    136-155 4653 CGGCGGGGGCAGCCCAGGC 4654 cGGcGGGGGcAGcccAGGcdTsdT sense
    136-155 4655 GCCUGGGCUGCCCCCGCCG 4656 GCCUGGGCUGCCCCCGCCGdTsdT antis
    140-159 4657 GGGGGCAGCCCAGGCAGCC 4658 GGGGGcAGcccAGGcAGccdTsdT sense
    140-159 4659 GGCUGCCUGGGCUGCCCCC 4660 GGCUGCCUGGGCUGCCCCCdTsdT antis
    165-184 4661 CCGCGGCCUGGGCCUGCGC 4662 ccGcGGccuGGGccuGcGcdTsdT sense
    165-184 4663 GCGCAGGCCCAGGCCGCGG 4664 GCGcAGGCCcAGGCCGCGGdTsdT antis
    170-189 4665 GCCUGGGCCUGCGCUCGGC 4666 GccuGGGccuGcGcucGGcdTsdT sense
    170-189 4667 GCCGAGCGCAGGCCCAGGC 4668 GCCGAGCGcAGGCCcAGGCdTsdT antis
    171-190 4669 CCUGGGCCUGCGCUCGGCG 4670 ccuGGGccuGcGcucGGcGdTsdT sense
    171-190 4671 CGCCGAGCGCAGGCCCAGG 4672 CGCCGAGCGcAGGCCcAGGdTsdT antis
    185-204 4673 CGGCGCCAUGAGCGGCGGC 4674 cGGcGccAuGAGcGGcGGcdTsdT sense
    185-204 4675 GCCGCCGCUCAUGGCGCCG 4676 GCCGCCGCUcAUGGCGCCGdTsdT antis
    201-220 4677 GGCGGGCCUUCGGGAGGCG 4678 GGcGGGccuucGGGAGGcGdTsdT sense
    201-220 4679 CGCCUCCCGAAGGCCCGCC 4680 CGCCUCCCGAAGGCCCGCCdTsdT antis
    214-233 4681 GAGGCGGCCCUGGGGGCUC 4682 GAGGcGGcccuGGGGGcucdTsdT sense
    214-233 4683 GAGCCCCCAGGGCCGCCUC 4684 GAGCCCCcAGGGCCGCCUCdTsdT antis
    215-234 4685 AGGCGGCCCUGGGGGCUCG 4686 AGGcGGcccuGGGGGcucGdTsdT sense
    215-234 4687 CGAGCCCCCAGGGCCGCCU 4688 CGAGCCCCcAGGGCCGCCUdTsdT antis
    216-235 4689 GGCGGCCCUGGGGGCUCGG 4690 GGcGGcccuGGGGGcucGGdTsdT sense
    216-235 4691 CCGAGCCCCCAGGGCCGCC 4692 CCGAGCCCCcAGGGCCGCCdTsdT antis
    227-246 4693 GGGCUCGGGCCGGGCGCGG 4694 GGGcucGGGccGGGcGcGGdTsdT sense
    227-246 4695 CCGCGCCCGGCCCGAGCCC 4696 CCGCGCCCGGCCCGAGCCCdTsdT antis
    229-248 4697 GCUCGGGCCGGGCGCGGAC 4698 GcucGGGccGGGcGcGGAcdTsdT sense
    229-248 4699 GUCCGCGCCCGGCCCGAGC 4700 GUCCGCGCCCGGCCCGAGCdTsdT antis
    230-249 4701 CUCGGGCCGGGCGCGGACC 4702 cucGGGccGGGcGcGGAccdTsdT sense
    230-249 4703 GGUCCGCGCCCGGCCCGAG 4704 GGUCCGCGCCCGGCCCGAGdTsdT antis
    290-309 4705 CGGCGGCCCCGGGGGCUCG 4706 cGGcGGccccGGGGGcucGdTsdT sense
    290-309 4707 CGAGCCCCCGGGGCCGCCG 4708 CGAGCCCCCGGGGCCGCCGdTsdT antis
    292-311 4709 GCGGCCCCGGGGGCUCGGC 4710 GcGGccccGGGGGcucGGcdTsdT sense
    292-311 4711 GCCGAGCCCCCGGGGCCGC 4712 GCCGAGCCCCCGGGGCCGCdTsdT antis
    293-312 4713 CGGCCCCGGGGGCUCGGCC 4714 cGGccccGGGGGcucGGccdTsdT sense
    293-312 4715 GGCCGAGCCCCCGGGGCCG 4716 GGCCGAGCCCCCGGGGCCGdTsdT antis
    299-318 4717 CGGGGGCUCGGCCUCUGGC 4718 cGGGGGcucGGccucuGGcdTsdT sense
    299-318 4719 GCCAGAGGCCGAGCCCCCG 4720 GCcAGAGGCCGAGCCCCCGdTsdT antis
    300-319 4721 GGGGGCUCGGCCUCUGGCC 4722 GGGGGcucGGccucuGGccdTsdT sense
    300-319 4723 GGCCAGAGGCCGAGCCCCC 4724 GGCcAGAGGCCGAGCCCCCdTsdT antis
    302-321 4725 GGGCUCGGCCUCUGGCCCA 4726 GGGcucGGccucuGGcccAdTsdT sense
    302-321 4727 UGGGCCAGAGGCCGAGCCC 4728 UGGGCcAGAGGCCGAGCCCdTsdT antis
    304-323 4729 GCUCGGCCUCUGGCCCAGG 4730 GcucGGccucuGGcccAGGdTsdT sense
    304-323 4731 CCUGGGCCAGAGGCCGAGC 4732 CCUGGGCcAGAGGCCGAGCdTsdT antis
    305-324 4733 CUCGGCCUCUGGCCCAGGA 4734 cucGGccucuGGcccAGGAdTsdT sense
    305-324 4735 UCCUGGGCCAGAGGCCGAG 4736 UCCUGGGCcAGAGGCCGAGdTsdT antis
    306-325 4737 UCGGCCUCUGGCCCAGGAG 4738 ucGGccucuGGcccAGGAGdTsdT sense
    306-325 4739 CUCCUGGGCCAGAGGCCGA 4740 CUCCUGGGCcAGAGGCCGAdTsdT antis
    307-326 4741 CGGCCUCUGGCCCAGGAGG 4742 cGGccucuGGcccAGGAGGdTsdT sense
    307-326 4743 CCUCCUGGGCCAGAGGCCG 4744 CCUCCUGGGCcAGAGGCCGdTsdT antis
    322-341 4745 GAGGCACUGGCGGCGGGAA 4746 GAGGcAcuGGcGGcGGGAAdTsdT sense
    322-341 4747 UUCCCGCCGCCAGUGCCUC 4748 UUCCCGCCGCcAGUGCCUCdTsdT antis
    339-358 4749 AAAGCGUCAGUCGGGGCUA 4750 AAAGcGucAGucGGGGcuAdTsdT sense
    339-358 4751 UAGCCCCGACUGACGCUUU 4752 uAGCCCCGACUGACGCUUUdTsdT antis
    345-364 4753 UCAGUCGGGGCUAUGGGUG 4754 ucAGucGGGGcuAuGGGuGdTsdT sense
    345-364 4755 CACCCAUAGCCCCGACUGA 4756 cACCcAuAGCCCCGACUGAdTsdT antis
    346-365 4757 CAGUCGGGGCUAUGGGUGG 4758 cAGucGGGGcuAuGGGuGGdTsdT sense
    346-365 4759 CCACCCAUAGCCCCGACUG 4760 CcACCcAuAGCCCCGACUGdTsdT antis
    350-369 4761 CGGGGCUAUGGGUGGGGGC 4762 cGGGGcuAuGGGuGGGGGcdTsdT sense
    350-369 4763 GCCCCCACCCAUAGCCCCG 4764 GCCCCcACCcAuAGCCCCGdTsdT antis
    374-393 4765 AGCCUCGAGCUCCGGGGGU 4766 AGccucGAGcuccGGGGGudTsdT sense
    374-393 4767 ACCCCCGGAGCUCGAGGCU 4768 ACCCCCGGAGCUCGAGGCUdTsdT antis
    378-397 4769 UCGAGCUCCGGGGGUGGCC 4770 ucGAGcuccGGGGGuGGccdTsdT sense
    378-397 4771 GGCCACCCCCGGAGCUCGA 4772 GGCcACCCCCGGAGCUCGAdTsdT antis
    379-398 4773 CGAGCUCCGGGGGUGGCCC 4774 cGAGcuccGGGGGuGGcccdTsdT sense
    379-398 4775 GGGCCACCCCCGGAGCUCG 4776 GGGCcACCCCCGGAGCUCGdTsdT antis
    384-403 4777 UCCGGGGGUGGCCCCAGCG 4778 uccGGGGGuGGccccAGcGdTsdT sense
    384-403 4779 CGCUGGGGCCACCCCCGGA 4780 CGCUGGGGCcACCCCCGGAdTsdT antis
    394-413 4781 GCCCCAGCGGCAGCGGCGG 4782 GccccAGcGGcAGcGGcGGdTsdT sense
    394-413 4783 CCGCCGCUGCCGCUGGGGC 4784 CCGCCGCUGCCGCUGGGGCdTsdT antis
    418-437 4785 GCAGCGGUGGCCCCGGCGC 4786 GcAGcGGuGGccccGGcGcdTsdT sense
    418-437 4787 GCGCCGGGGCCACCGCUGC 4788 GCGCCGGGGCcACCGCUGCdTsdT antis
    419-438 4789 CAGCGGUGGCCCCGGCGCG 4790 cAGcGGuGGccccGGcGcGdTsdT sense
    419-438 4791 CGCGCCGGGGCCACCGCUG 4792 CGCGCCGGGGCcACCGCUGdTsdT antis
    421-440 4793 GCGGUGGCCCCGGCGCGGG 4794 GcGGuGGccccGGcGcGGGdTsdT sense
    421-440 4795 CCCGCGCCGGGGCCACCGC 4796 CCCGCGCCGGGGCcACCGCdTsdT antis
    422-441 4797 CGGUGGCCCCGGCGCGGGC 4798 cGGuGGccccGGcGcGGGcdTsdT sense
    422-441 4799 GCCCGCGCCGGGGCCACCG 4800 GCCCGCGCCGGGGCcACCGdTsdT antis
    423-442 4801 GGUGGCCCCGGCGCGGGCA 4802 GGuGGccccGGcGcGGGcAdTsdT sense
    423-442 4803 UGCCCGCGCCGGGGCCACC 4804 UGCCCGCGCCGGGGCcACCdTsdT antis
    424-443 4805 GUGGCCCCGGCGCGGGCAC 4806 GuGGccccGGcGcGGGcAcdTsdT sense
    424-443 4807 GUGCCCGCGCCGGGGCCAC 4808 GUGCCCGCGCCGGGGCcACdTsdT antis
    443-462 4809 UAGCUUCCCGCCGCCGGGA 4810 uAGcuucccGccGccGGGAdTsdT sense
    443-462 4811 UCCCGGCGGCGGGAAGCUA 4812 UCCCGGCGGCGGGAAGCuAdTsdT antis
    450-469 4813 CCGCCGCCGGGAGUGAAGC 4814 ccGccGccGGGAGuGAAGcdTsdT sense
    450-469 4815 GCUUCACUCCCGGCGGCGG 4816 GCUUcACUCCCGGCGGCGGdTsdT antis
    455-474 4817 GCCGGGAGUGAAGCUGGGC 4818 GccGGGAGuGAAGcuGGGcdTsdT sense
    455-474 4819 GCCCAGCUUCACUCCCGGC 4820 GCCcAGCUUcACUCCCGGCdTsdT antis
    457-476 4821 CGGGAGUGAAGCUGGGCCG 4822 cGGGAGuGAAGcuGGGccGdTsdT sense
    457-476 4823 CGGCCCAGCUUCACUCCCG 4824 CGGCCcAGCUUcACUCCCGdTsdT antis
    462-481 4825 GUGAAGCUGGGCCGUGACA 4826 GuGAAGcuGGGccGuGAcAdTsdT sense
    462-481 4827 UGUCACGGCCCAGCUUCAC 4828 UGUcACGGCCcAGCUUcACdTsdT antis
    467-486 4829 GCUGGGCCGUGACAGCGGG 4830 GcuGGGccGuGAcAGcGGGdTsdT sense
    467-486 4831 CCCGCUGUCACGGCCCAGC 4832 CCCGCUGUcACGGCCcAGCdTsdT antis
    478-497 4833 ACAGCGGGAAGGUGACCAC 4834 AcAGcGGGAAGGuGAccAcdTsdT sense
    478-497 4835 GUGGUCACCUUCCCGCUGU 4836 GUGGUcACCUUCCCGCUGUdTsdT antis
    482-501 4837 CGGGAAGGUGACCACAGUG 4838 cGGGAAGGuGAccAcAGuGdTsdT sense
    482-501 4839 CACUGUGGUCACCUUCCCG 4840 cACUGUGGUcACCUUCCCGdTsdT antis
    498-517 4841 GUGGUAGCCACUGUAGGCC 4842 GuGGuAGccAcuGuAGGccdTsdT sense
    498-517 4843 GGCCUACAGUGGCUACCAC 4844 GGCCuAcAGUGGCuACcACdTsdT antis
    499-518 4845 UGGUAGCCACUGUAGGCCA 4846 uGGuAGccAcuGuAGGccAdTsdT sense
    499-518 4847 UGGCCUACAGUGGCUACCA 4848 UGGCCuAcAGUGGCuACcAdTsdT antis
    500-519 4849 GGUAGCCACUGUAGGCCAA 4850 GGuAGccAcuGuAGGccAAdTsdT sense
    500-519 4851 UUGGCCUACAGUGGCUACC 4852 UUGGCCuAcAGUGGCuACCdTsdT antis
    501-520 4853 GUAGCCACUGUAGGCCAAG 4854 GuAGccAcuGuAGGccAAGdTsdT sense
    501-520 4855 CUUGGCCUACAGUGGCUAC 4856 CUUGGCCuAcAGUGGCuACdTsdT antis
    508-527 4857 CUGUAGGCCAAGGCCCAGA 4858 cuGuAGGccAAGGcccAGAdTsdT sense
    508-527 4859 UCUGGGCCUUGGCCUACAG 4860 UCUGGGCCUUGGCCuAcAGdTsdT antis
    514-533 4861 GCCAAGGCCCAGAGCGUUC 4862 GccAAGGcccAGAGcGuucdTsdT sense
    514-533 4863 GAACGCUCUGGGCCUUGGC 4864 GAACGCUCUGGGCCUUGGCdTsdT antis
    515-534 4865 CCAAGGCCCAGAGCGUUCC 4866 ccAAGGcccAGAGcGuuccdTsdT sense
    515-534 4867 GGAACGCUCUGGGCCUUGG 4868 GGAACGCUCUGGGCCUUGGdTsdT antis
    540-559 4869 GUGGCUUACACUGACAUCA 4870 GuGGcuuAcAcuGAcAucAdTsdT sense
    540-559 4871 UGAUGUCAGUGUAAGCCAC 4872 UGAUGUcAGUGuAAGCcACdTsdT antis
    541-560 4873 UGGCUUACACUGACAUCAA 4874 uGGcuuAcAcuGAcAucAAdTsdT sense
    541-560 4875 UUGAUGUCAGUGUAAGCCA 4876 UUGAUGUcAGUGuAAGCcAdTsdT antis
    543-562 4877 GCUUACACUGACAUCAAAG 4878 GcuuAcAcuGAcAucAAAGdTsdT sense
    543-562 4879 CUUUGAUGUCAGUGUAAGC 4880 CUUUGAUGUcAGUGuAAGCdTsdT antis
    546-565 4881 UACACUGACAUCAAAGUGA 4882 uAcAcuGAcAucAAAGuGAdTsdT sense
    546-565 4883 UCACUUUGAUGUCAGUGUA 4884 UcACUUUGAUGUcAGUGuAdTsdT antis
    594-613 4885 CAGGCACGGCUGGCAGAGA 4886 cAGGcAcGGcuGGcAGAGAdTsdT sense
    594-613 4887 UCUCUGCCAGCCGUGCCUG 4888 UCUCUGCcAGCCGUGCCUGdTsdT antis
    605-624 4889 GGCAGAGACGAGGGAACUG 4890 GGcAGAGAcGAGGGAAcuGdTsdT sense
    605-624 4891 CAGUUCCCUCGUCUCUGCC 4892 cAGUUCCCUCGUCUCUGCCdTsdT antis
    607-626 4893 CAGAGACGAGGGAACUGGU 4894 cAGAGAcGAGGGAAcuGGudTsdT sense
    607-626 4895 ACCAGUUCCCUCGUCUCUG 4896 ACcAGUUCCCUCGUCUCUGdTsdT antis
    617-636 4897 GGAACUGGUGGCCAUCAAG 4898 GGAAcuGGuGGccAucAAGdTsdT sense
    617-636 4899 CUUGAUGGCCACCAGUUCC 4900 CUUGAUGGCcACcAGUUCCdTsdT antis
    618-637 4901 GAACUGGUGGCCAUCAAGA 4902 GAAcuGGuGGccAucAAGAdTsdT sense
    618-637 4903 UCUUGAUGGCCACCAGUUC 4904 UCUUGAUGGCcACcAGUUCdTsdT antis
    619-638 4905 AACUGGUGGCCAUCAAGAA 4906 AAcuGGuGGccAucAAGAAdTsdT sense
    619-638 4907 UUCUUGAUGGCCACCAGUU 4908 UUCUUGAUGGCcACcAGUUdTsdT antis
    624-643 4909 GUGGCCAUCAAGAAGGUUC 4910 GuGGccAucAAGAAGGuucdTsdT sense
    624-643 4911 GAACCUUCUUGAUGGCCAC 4912 GAACCUUCUUGAUGGCcACdTsdT antis
    625-644 4913 UGGCCAUCAAGAAGGUUCU 4914 uGGccAucAAGAAGGuucudTsdT sense
    625-644 4915 AGAACCUUCUUGAUGGCCA 4916 AGAACCUUCUUGAUGGCcAdTsdT antis
    647-666 4917 GGACAAAAGGUUCAAGAAC 4918 GGAcAAAAGGuucAAGAAcdTsdT sense
    647-666 4919 GUUCUUGAACCUUUUGUCC 4920 GUUCUUGAACCUUUUGUCCdTsdT antis
    648-667 4921 GACAAAAGGUUCAAGAACC 4922 GAcAAAAGGuucAAGAAccdTsdT sense
    648-667 4923 GGUUCUUGAACCUUUUGUC 4924 GGUUCUUGAACCUUUUGUCdTsdT antis
    666-685 4925 CGAGAACUGCAGAUUAUGC 4926 cGAGAAcuGcAGAuuAuGcdTsdT sense
    666-685 4927 GCAUAAUCUGCAGUUCUCG 4928 GcAuAAUCUGcAGUUCUCGdTsdT antis
    713-732 4929 GCUGCGGUACUUUUUCUAC 4930 GcuGcGGuAcuuuuucuAcdTsdT sense
    713-732 4931 GUAGAAAAAGUACCGCAGC 4932 GuAGAAAAAGuACCGcAGCdTsdT antis
    717-736 4933 CGGUACUUUUUCUACUCCA 4934 cGGuAcuuuuucuAcuccAdTsdT sense
    717-736 4935 UGGAGUAGAAAAAGUACCG 4936 UGGAGuAGAAAAAGuACCGdTsdT antis
    739-758 4937 GGGAGAAGAAGGACGAGCU 4938 GGGAGAAGAAGGAcGAGcudTsdT sense
    739-758 4939 AGCUCGUCCUUCUUCUCCC 4940 AGCUCGUCCUUCUUCUCCCdTsdT antis
    740-759 4941 GGAGAAGAAGGACGAGCUG 4942 GGAGAAGAAGGAcGAGcuGdTsdT sense
    740-759 4943 CAGCUCGUCCUUCUUCUCC 4944 cAGCUCGUCCUUCUUCUCCdTsdT antis
    794-813 4945 GGUGUACCGAGUGGCCCGC 4946 GGuGuAccGAGuGGcccGcdTsdT sense
    794-813 4947 GCGGGCCACUCGGUACACC 4948 GCGGGCcACUCGGuAcACCdTsdT antis
    798-817 4949 UACCGAGUGGCCCGCCACU 4950 uAccGAGuGGcccGccAcudTsdT sense
    798-817 4951 AGUGGCGGGCCACUCGGUA 4952 AGUGGCGGGCcACUCGGuAdTsdT antis
    822-841 4953 AAGGCCAAGCUGAUCACCC 4954 AAGGccAAGcuGAucAcccdTsdT sense
    822-841 4955 GGGUGAUCAGCUUGGCCUU 4956 GGGUGAUcAGCUUGGCCUUdTsdT antis
    823-842 4957 AGGCCAAGCUGAUCACCCC 4958 AGGccAAGcuGAucAccccdTsdT sense
    823-842 4959 GGGGUGAUCAGCUUGGCCU 4960 GGGGUGAUcAGCUUGGCCUdTsdT antis
    846-865 4961 AUCUACAUCAAGGUGUACA 4962 AucuAcAucAAGGuGuAcAdTsdT sense
    846-865 4963 UGUACACCUUGAUGUAGAU 4964 UGuAcACCUUGAUGuAGAUdTsdT antis
    847-866 4965 UCUACAUCAAGGUGUACAU 4966 ucuAcAucAAGGuGuAcAudTsdT sense
    847-866 4967 AUGUACACCUUGAUGUAGA 4968 AUGuAcACCUUGAUGuAGAdTsdT antis
    848-867 4969 CUACAUCAAGGUGUACAUG 4970 cuAcAucAAGGuGuAcAuGdTsdT sense
    848-867 4971 CAUGUACACCUUGAUGUAG 4972 cAUGuAcACCUUGAUGuAGdTsdT antis
    849-868 4973 UACAUCAAGGUGUACAUGU 4974 uAcAucAAGGuGuAcAuGudTsdT sense
    849-868 4975 ACAUGUACACCUUGAUGUA 4976 AcAUGuAcACCUUGAUGuAdTsdT antis
    889-908 4977 CCUACAUCCACUCCCAAGG 4978 ccuAcAuccAcucccAAGGdTsdT sense
    889-908 4979 CCUUGGGAGUGGAUGUAGG 4980 CCUUGGGAGUGGAUGuAGGdTsdT antis
    892-911 4981 ACAUCCACUCCCAAGGUGU 4982 AcAuccAcucccAAGGuGudTsdT sense
    892-911 4983 ACACCUUGGGAGUGGAUGU 4984 AcACCUUGGGAGUGGAUGUdTsdT antis
    893-912 4985 CAUCCACUCCCAAGGUGUG 4986 cAuccAcucccAAGGuGuGdTsdT sense
    893-912 4987 CACACCUUGGGAGUGGAUG 4988 cAcACCUUGGGAGUGGAUGdTsdT antis
    904-923 4989 AAGGUGUGUGUCACCGUGA 4990 AAGGuGuGuGucAccGuGAdTsdT sense
    904-923 4991 UCACGGUGACACACACCUU 4992 UcACGGUGAcAcAcACCUUdTsdT antis
    905-924 4993 AGGUGUGUGUCACCGUGAC 4994 AGGuGuGuGucAccGuGAcdTsdT sense
    905-924 4995 GUCACGGUGACACACACCU 4996 GUcACGGUGAcAcAcACCUdTsdT antis
    906-925 4997 GGUGUGUGUCACCGUGACA 4998 GGuGuGuGucAccGuGAcAdTsdT sense
    906-925 4999 UGUCACGGUGACACACACC 5000 UGUcACGGUGAcAcAcACCdTsdT antis
    907-926 5001 GUGUGUGUCACCGUGACAU 5002 GuGuGuGucAccGuGAcAudTsdT sense
    907-926 5003 AUGUCACGGUGACACACAC 5004 AUGUcACGGUGAcAcAcACdTsdT antis
    908-927 5005 UGUGUGUCACCGUGACAUC 5006 uGuGuGucAccGuGAcAucdTsdT sense
    908-927 5007 GAUGUCACGGUGACACACA 5008 GAUGUcACGGUGAcAcAcAdTsdT antis
    909-928 5009 GUGUGUCACCGUGACAUCA 5010 GuGuGucAccGuGAcAucAdTsdT sense
    909-928 5011 UGAUGUCACGGUGACACAC 5012 UGAUGUcACGGUGAcAcACdTsdT antis
    910-929 5013 UGUGUCACCGUGACAUCAA 5014 uGuGucAccGuGAcAucAAdTsdT sense
    910-929 5015 UUGAUGUCACGGUGACACA 5016 UUGAUGUcACGGUGAcAcAdTsdT antis
    919-938 5017 GUGACAUCAAGCCCCAGAA 5018 GuGAcAucAAGccccAGAAdTsdT sense
    919-938 5019 UUCUGGGGCUUGAUGUCAC 5020 UUCUGGGGCUUGAUGUcACdTsdT antis
    946-965 5021 UGGACCCUGACACUGCUGU 5022 uGGAcccuGAcAcuGcuGudTsdT sense
    946-965 5023 ACAGCAGUGUCAGGGUCCA 5024 AcAGcAGUGUcAGGGUCcAdTsdT antis
    950-969 5025 CCCUGACACUGCUGUCCUC 5026 cccuGAcAcuGcuGuccucdTsdT sense
    950-969 5027 GAGGACAGCAGUGUCAGGG 5028 GAGGAcAGcAGUGUcAGGGdTsdT antis
    957-976 5029 ACUGCUGUCCUCAAGCUCU 5030 AcuGcuGuccucAAGcucudTsdT sense
    957-976 5031 AGAGCUUGAGGACAGCAGU 5032 AGAGCUUGAGGAcAGcAGUdTsdT antis
    961-980 5033 CUGUCCUCAAGCUCUGCGA 5034 cuGuccucAAGcucuGcGAdTsdT sense
    961-980 5035 UCGCAGAGCUUGAGGACAG 5036 UCGcAGAGCUUGAGGAcAGdTsdT antis
    962-981 5037 UGUCCUCAAGCUCUGCGAU 5038 uGuccucAAGcucuGcGAudTsdT sense
    962-981 5039 AUCGCAGAGCUUGAGGACA 5040 AUCGcAGAGCUUGAGGAcAdTsdT antis
    1020-1039 5041 GUGUCCUACAUCUGCUCUC 5042 GuGuccuAcAucuGcucucdTsdT sense
    1020-1039 5043 GAGAGCAGAUGUAGGACAC 5044 GAGAGcAGAUGuAGGAcACdTsdT antis
    1029-1048 5045 AUCUGCUCUCGGUACUACC 5046 AucuGcucucGGuAcuAccdTsdT sense
    1029-1048 5047 GGUAGUACCGAGAGCAGAU 5048 GGuAGuACCGAGAGcAGAUdTsdT antis
    1048-1067 5049 GUGCUCCAGAACUCAUCUU 5050 GuGcuccAGAAcucAucuudTsdT sense
    1048-1067 5051 AAGAUGAGUUCUGGAGCAC 5052 AAGAUGAGUUCUGGAGcACdTsdT antis
    1049-1068 5053 UGCUCCAGAACUCAUCUUU 5054 uGcuccAGAAcucAucuuudTsdT sense
    1049-1068 5055 AAAGAUGAGUUCUGGAGCA 5056 AAAGAUGAGUUCUGGAGcAdTsdT antis
    1050-1069 5057 GCUCCAGAACUCAUCUUUG 5058 GcuccAGAAcucAucuuuGdTsdT sense
    1050-1069 5059 CAAAGAUGAGUUCUGGAGC 5060 cAAAGAUGAGUUCUGGAGCdTsdT antis
    1059-1078 5061 CUCAUCUUUGGAGCCACAG 5062 cucAucuuuGGAGccAcAGdTsdT sense
    1059-1078 5063 CUGUGGCUCCAAAGAUGAG 5064 CUGUGGCUCcAAAGAUGAGdTsdT antis
    1087-1106 5065 CGUCCAUCGAUGUGUGGUC 5066 cGuccAucGAuGuGuGGucdTsdT sense
    1087-1106 5067 GACCACACAUCGAUGGACG 5068 GACcAcAcAUCGAUGGACGdTsdT antis
    1096-1115 5069 AUGUGUGGUCGGCUGGCUG 5070 AuGuGuGGucGGcuGGcuGdTsdT sense
    1096-1115 5071 CAGCCAGCCGACCACACAU 5072 cAGCcAGCCGACcAcAcAUdTsdT antis
    1130-1149 5073 ACUUCUCGGCCAGCCCAUC 5074 AcuucucGGccAGcccAucdTsdT sense
    1130-1149 5075 GAUGGGCUGGCCGAGAAGU 5076 GAUGGGCUGGCCGAGAAGUdTsdT antis
    1134-1153 5077 CUCGGCCAGCCCAUCUUCC 5078 cucGGccAGcccAucuuccdTsdT sense
    1134-1153 5079 GGAAGAUGGGCUGGCCGAG 5080 GGAAGAUGGGCUGGCCGAGdTsdT antis
    1141-1160 5081 AGCCCAUCUUCCCUGGGGA 5082 AGcccAucuucccuGGGGAdTsdT sense
    1141-1160 5083 UCCCCAGGGAAGAUGGGCU 5084 UCCCcAGGGAAGAUGGGCUdTsdT antis
    1144-1163 5085 CCAUCUUCCCUGGGGACAG 5086 ccAucuucccuGGGGAcAGdTsdT sense
    1144-1163 5087 CUGUCCCCAGGGAAGAUGG 5088 CUGUCCCcAGGGAAGAUGGdTsdT antis
    1151-1170 5089 CCCUGGGGACAGUGGGGUG 5090 cccuGGGGAcAGuGGGGuGdTsdT sense
    1151-1170 5091 CACCCCACUGUCCCCAGGG 5092 cACCCcACUGUCCCcAGGGdTsdT antis
    1156-1175 5093 GGGACAGUGGGGUGGACCA 5094 GGGAcAGuGGGGuGGAccAdTsdT sense
    1156-1175 5095 UGGUCCACCCCACUGUCCC 5096 UGGUCcACCCcACUGUCCCdTsdT antis
    1157-1176 5097 GGACAGUGGGGUGGACCAG 5098 GGAcAGuGGGGuGGAccAGdTsdT sense
    1157-1176 5099 CUGGUCCACCCCACUGUCC 5100 CUGGUCcACCCcACUGUCCdTsdT antis
    1158-1177 5101 GACAGUGGGGUGGACCAGC 5102 GAcAGuGGGGuGGAccAGcdTsdT sense
    1158-1177 5103 GCUGGUCCACCCCACUGUC 5104 GCUGGUCcACCCcACUGUCdTsdT antis
    1159-1178 5105 ACAGUGGGGUGGACCAGCU 5106 AcAGuGGGGuGGAccAGcudTsdT sense
    1159-1178 5107 AGCUGGUCCACCCCACUGU 5108 AGCUGGUCcACCCcACUGUdTsdT antis
    1160-1179 5109 CAGUGGGGUGGACCAGCUU 5110 cAGuGGGGuGGAccAGcuudTsdT sense
    1160-1179 5111 AAGCUGGUCCACCCCACUG 5112 AAGCUGGUCcACCCcACUGdTsdT antis
    1244-1263 5113 UACGGAGUUCAAGUUCCCC 5114 uAcGGAGuucAAGuuccccdTsdT sense
    1244-1263 5115 GGGGAACUUGAACUCCGUA 5116 GGGGAACUUGAACUCCGuAdTsdT antis
    1246-1265 5117 CGGAGUUCAAGUUCCCCCA 5118 cGGAGuucAAGuucccccAdTsdT sense
    1246-1265 5119 UGGGGGAACUUGAACUCCG 5120 UGGGGGAACUUGAACUCCGdTsdT antis
    1273-1292 5121 CUCACCCUUGGACAAAGGU 5122 cucAcccuuGGAcAAAGGudTsdT sense
    1273-1292 5123 ACCUUUGUCCAAGGGUGAG 5124 ACCUUUGUCcAAGGGUGAGdTsdT antis
    1275-1294 5125 CACCCUUGGACAAAGGUGU 5126 cAcccuuGGAcAAAGGuGudTsdT sense
    1275-1294 5127 ACACCUUUGUCCAAGGGUG 5128 AcACCUUUGUCcAAGGGUGdTsdT antis
    1278-1297 5129 CCUUGGACAAAGGUGUUCA 5130 ccuuGGAcAAAGGuGuucAdTsdT sense
    1278-1297 5131 UGAACACCUUUGUCCAAGG 5132 UGAAcACCUUUGUCcAAGGdTsdT antis
    1279-1298 5133 CUUGGACAAAGGUGUUCAA 5134 cuuGGAcAAAGGuGuucAAdTsdT sense
    1279-1298 5135 UUGAACACCUUUGUCCAAG 5136 UUGAAcACCUUUGUCcAAGdTsdT antis
    1288-1307 5137 AGGUGUUCAAAUCUUCAAA 5138 AGGuGuucAAAucuucAAAdTsdT sense
    1288-1307 5139 UUUGAAGAUUUGAACACCU 5140 UUUGAAGAUUUGAAcACCUdTsdT antis
    1291-1310 5141 UGUUCAAAUCUUCAAAGAC 5142 uGuucAAAucuucAAAGAcdTsdT sense
    1291-1310 5143 GUCUUUGAAGAUUUGAACA 5144 GUCUUUGAAGAUUUGAAcAdTsdT antis
    1292-1311 5145 GUUCAAAUCUUCAAAGACA 5146 GuucAAAucuucAAAGAcAdTsdT sense
    1292-1311 5147 UGUCUUUGAAGAUUUGAAC 5148 UGUCUUUGAAGAUUUGAACdTsdT antis
    1293-1312 5149 UUCAAAUCUUCAAAGACAC 5150 uucAAAucuucAAAGAcAcdTsdT sense
    1293-1312 5151 GUGUCUUUGAAGAUUUGAA 5152 GUGUCUUUGAAGAUUUGAAdTsdT antis
    1294-1313 5153 UCAAAUCUUCAAAGACACC 5154 ucAAAucuucAAAGAcAccdTsdT sense
    1294-1313 5155 GGUGUCUUUGAAGAUUUGA 5156 GGUGUCUUUGAAGAUUUGAdTsdT antis
    1314-1333 5157 CCUGAGGCCAUUGCACUCU 5158 ccuGAGGccAuuGcAcucudTsdT sense
    1314-1333 5159 AGAGUGCAAUGGCCUCAGG 5160 AGAGUGcAAUGGCCUcAGGdTsdT antis
    1320-1339 5161 GCCAUUGCACUCUGCUCUA 5162 GccAuuGcAcucuGcucuAdTsdT sense
    1320-1339 5163 UAGAGCAGAGUGCAAUGGC 5164 uAGAGcAGAGUGcAAUGGCdTsdT antis
    1336-1355 5165 CUAGCCUACUGGAGUACAC 5166 cuAGccuAcuGGAGuAcAcdTsdT sense
    1336-1355 5167 GUGUACUCCAGUAGGCUAG 5168 GUGuACUCcAGuAGGCuAGdTsdT antis
    1353-1372 5169 ACGCCAUCCUCAAGGCUCU 5170 AcGccAuccucAAGGcucudTsdT sense
    1353-1372 5171 AGAGCCUUGAGGAUGGCGU 5172 AGAGCCUUGAGGAUGGCGUdTsdT antis
    1355-1374 5173 GCCAUCCUCAAGGCUCUCC 5174 GccAuccucAAGGcucuccdTsdT sense
    1355-1374 5175 GGAGAGCCUUGAGGAUGGC 5176 GGAGAGCCUUGAGGAUGGCdTsdT antis
    1359-1378 5177 UCCUCAAGGCUCUCCCCAC 5178 uccucAAGGcucuccccAcdTsdT sense
    1359-1378 5179 GUGGGGAGAGCCUUGAGGA 5180 GUGGGGAGAGCCUUGAGGAdTsdT antis
    1372-1391 5181 CCCCACUCGAGGCUUGUGC 5182 ccccAcucGAGGcuuGuGcdTsdT sense
    1372-1391 5183 GCACAAGCCUCGAGUGGGG 5184 GcAcAAGCCUCGAGUGGGGdTsdT antis
    1373-1392 5185 CCCACUCGAGGCUUGUGCC 5186 cccAcucGAGGcuuGuGccdTsdT sense
    1373-1392 5187 GGCACAAGCCUCGAGUGGG 5188 GGcAcAAGCCUCGAGUGGGdTsdT antis
    1374-1393 5189 CCACUCGAGGCUUGUGCCC 5190 ccAcucGAGGcuuGuGcccdTsdT sense
    1374-1393 5191 GGGCACAAGCCUCGAGUGG 5192 GGGcAcAAGCCUCGAGUGGdTsdT antis
    1376-1395 5193 ACUCGAGGCUUGUGCCCAC 5194 AcucGAGGcuuGuGcccAcdTsdT sense
    1376-1395 5195 GUGGGCACAAGCCUCGAGU 5196 GUGGGcAcAAGCCUCGAGUdTsdT antis
    1377-1396 5197 CUCGAGGCUUGUGCCCACA 5198 cucGAGGcuuGuGcccAcAdTsdT sense
    1377-1396 5199 UGUGGGCACAAGCCUCGAG 5200 UGUGGGcAcAAGCCUCGAGdTsdT antis
    1378-1397 5201 UCGAGGCUUGUGCCCACAG 5202 ucGAGGcuuGuGcccAcAGdTsdT sense
    1378-1397 5203 CUGUGGGCACAAGCCUCGA 5204 CUGUGGGcAcAAGCCUCGAdTsdT antis
    1389-1408 5205 GCCCACAGCUUCUUCGAUG 5206 GcccAcAGcuucuucGAuGdTsdT sense
    1389-1408 5207 CAUCGAAGAAGCUGUGGGC 5208 cAUCGAAGAAGCUGUGGGCdTsdT antis
    1391-1410 5209 CCACAGCUUCUUCGAUGAA 5210 ccAcAGcuucuucGAuGAAdTsdT sense
    1391-1410 5211 UUCAUCGAAGAAGCUGUGG 5212 UUcAUCGAAGAAGCUGUGGdTsdT antis
    1423-1442 5213 GAGCCCAGCUCCCCAACGA 5214 GAGcccAGcuccccAAcGAdTsdT sense
    1423-1442 5215 UCGUUGGGGAGCUGGGCUC 5216 UCGUUGGGGAGCUGGGCUCdTsdT antis
    1469-1488 5217 CAGUCCUGGUGAACUGUCC 5218 cAGuccuGGuGAAcuGuccdTsdT sense
    1469-1488 5219 GGACAGUUCACCAGGACUG 5220 GGAcAGUUcACcAGGACUGdTsdT antis
    1484-1503 5221 GUCCAUCCAACCAUCUCUC 5222 GuccAuccAAccAucucucdTsdT sense
    1484-1503 5223 GAGAGAUGGUUGGAUGGAC 5224 GAGAGAUGGUUGGAUGGACdTsdT antis
    1496-1515 5225 AUCUCUCAAUGCCAUUCUC 5226 AucucucAAuGccAuucucdTsdT sense
    1496-1515 5227 GAGAAUGGCAUUGAGAGAU 5228 GAGAAUGGcAUUGAGAGAUdTsdT antis
    1498-1517 5229 CUCUCAAUGCCAUUCUCAU 5230 cucucAAuGccAuucucAudTsdT sense
    1498-1517 5231 AUGAGAAUGGCAUUGAGAG 5232 AUGAGAAUGGcAUUGAGAGdTsdT antis
    1499-1518 5233 UCUCAAUGCCAUUCUCAUC 5234 ucucAAuGccAuucucAucdTsdT sense
    1499-1518 5235 GAUGAGAAUGGCAUUGAGA 5236 GAUGAGAAUGGcAUUGAGAdTsdT antis
    1502-1521 5237 CAAUGCCAUUCUCAUCCCU 5238 cAAuGccAuucucAucccudTsdT sense
    1502-1521 5239 AGGGAUGAGAAUGGCAUUG 5240 AGGGAUGAGAAUGGcAUUGdTsdT antis
    1541-1560 5241 AGGCCCUGCUUCUCCCCUC 5242 AGGcccuGcuucuccccucdTsdT sense
    1541-1560 5243 GAGGGGAGAAGCAGGGCCU 5244 GAGGGGAGAAGcAGGGCCUdTsdT antis
    1542-1561 5245 GGCCCUGCUUCUCCCCUCA 5246 GGcccuGcuucuccccucAdTsdT sense
    1542-1561 5247 UGAGGGGAGAAGCAGGGCC 5248 UGAGGGGAGAAGcAGGGCCdTsdT antis
    1548-1567 5249 GCUUCUCCCCUCACCACUU 5250 GcuucuccccucAccAcuudTsdT sense
    1548-1567 5251 AAGUGGUGAGGGGAGAAGC 5252 AAGUGGUGAGGGGAGAAGCdTsdT antis
    1549-1568 5253 CUUCUCCCCUCACCACUUC 5254 cuucuccccucAccAcuucdTsdT sense
    1549-1568 5255 GAAGUGGUGAGGGGAGAAG 5256 GAAGUGGUGAGGGGAGAAGdTsdT antis
    1552-1571 5257 CUCCCCUCACCACUUCCUA 5258 cuccccucAccAcuuccuAdTsdT sense
    1552-1571 5259 UAGGAAGUGGUGAGGGGAG 5260 uAGGAAGUGGUGAGGGGAGdTsdT antis
    1557-1576 5261 CUCACCACUUCCUACAACC 5262 cucAccAcuuccuAcAAccdTsdT sense
    1557-1576 5263 GGUUGUAGGAAGUGGUGAG 5264 GGUUGuAGGAAGUGGUGAGdTsdT antis
    1575-1594 5265 CCAUCCUCACAAGCUUUAA 5266 ccAuccucAcAAGcuuuAAdTsdT sense
    1575-1594 5267 UUAAAGCUUGUGAGGAUGG 5268 UuAAAGCUUGUGAGGAUGGdTsdT antis
    1600-1619 5269 CUCAGACUGGCCAAGAUUG 5270 cucAGAcuGGccAAGAuuGdTsdT sense
    1600-1619 5271 CAAUCUUGGCCAGUCUGAG 5272 cAAUCUUGGCcAGUCUGAGdTsdT antis
    1616-1635 5273 UUGGCAGCCAUCUGAUGCC 5274 uuGGcAGccAucuGAuGccdTsdT sense
    1616-1635 5275 GGCAUCAGAUGGCUGCCAA 5276 GGcAUcAGAUGGCUGCcAAdTsdT antis
    1617-1636 5277 UGGCAGCCAUCUGAUGCCA 5278 uGGcAGccAucuGAuGccAdTsdT sense
    1617-1636 5279 UGGCAUCAGAUGGCUGCCA 5280 UGGcAUcAGAUGGCUGCcAdTsdT antis
    1618-1637 5281 GGCAGCCAUCUGAUGCCAC 5282 GGcAGccAucuGAuGccAcdTsdT sense
    1618-1637 5283 GUGGCAUCAGAUGGCUGCC 5284 GUGGcAUcAGAUGGCUGCCdTsdT antis
    1619-1638 5285 GCAGCCAUCUGAUGCCACA 5286 GcAGccAucuGAuGccAcAdTsdT sense
    1619-1638 5287 UGUGGCAUCAGAUGGCUGC 5288 UGUGGcAUcAGAUGGCUGCdTsdT antis
    1622-1641 5289 GCCAUCUGAUGCCACAACU 5290 GccAucuGAuGccAcAAcudTsdT sense
    1622-1641 5291 AGUUGUGGCAUCAGAUGGC 5292 AGUUGUGGcAUcAGAUGGCdTsdT antis
    1647-1666 5293 CUCGCUAGCUCUUCCUGAG 5294 cucGcuAGcucuuccuGAGdTsdT sense
    1647-1666 5295 CUCAGGAAGAGCUAGCGAG 5296 CUcAGGAAGAGCuAGCGAGdTsdT antis
    1648-1667 5297 UCGCUAGCUCUUCCUGAGG 5298 ucGcuAGcucuuccuGAGGdTsdT sense
    1648-1667 5299 CCUCAGGAAGAGCUAGCGA 5300 CCUcAGGAAGAGCuAGCGAdTsdT antis
    1649-1668 5301 CGCUAGCUCUUCCUGAGGG 5302 cGcuAGcucuuccuGAGGGdTsdT sense
    1649-1668 5303 CCCUCAGGAAGAGCUAGCG 5304 CCCUcAGGAAGAGCuAGCGdTsdT antis
    1658-1677 5305 UUCCUGAGGGCCCCACCGA 5306 uuccuGAGGGccccAccGAdTsdT sense
    1658-1677 5307 UCGGUGGGGCCCUCAGGAA 5308 UCGGUGGGGCCCUcAGGAAdTsdT antis
    1661-1680 5309 CUGAGGGCCCCACCGACUA 5310 cuGAGGGccccAccGAcuAdTsdT sense
    1661-1680 5311 UAGUCGGUGGGGCCCUCAG 5312 uAGUCGGUGGGGCCCUcAGdTsdT antis
    1662-1681 5313 UGAGGGCCCCACCGACUAC 5314 uGAGGGccccAccGAcuAcdTsdT sense
    1662-1681 5315 GUAGUCGGUGGGGCCCUCA 5316 GuAGUCGGUGGGGCCCUcAdTsdT antis
    1663-1682 5317 GAGGGCCCCACCGACUACC 5318 GAGGGccccAccGAcuAccdTsdT sense
    1663-1682 5319 GGUAGUCGGUGGGGCCCUC 5320 GGuAGUCGGUGGGGCCCUCdTsdT antis
    1800-1819 5321 AUCUAGGCCUCCCUCAGCA 5322 AucuAGGccucccucAGcAdTsdT sense
    1800-1819 5323 UGCUGAGGGAGGCCUAGAU 5324 UGCUGAGGGAGGCCuAGAUdTsdT antis
    1807-1826 5325 CCUCCCUCAGCAGCCUAAC 5326 ccucccucAGcAGccuAAcdTsdT sense
    1807-1826 5327 GUUAGGCUGCUGAGGGAGG 5328 GUuAGGCUGCUGAGGGAGGdTsdT antis
    1819-1838 5329 GCCUAACCUCUGUGGUGGG 5330 GccuAAccucuGuGGuGGGdTsdT sense
    1819-1838 5331 CCCACCACAGAGGUUAGGC 5332 CCcACcAcAGAGGUuAGGCdTsdT antis
    1856-1875 5333 AACUGUUUGUAGGGGAGGG 5334 AAcuGuuuGuAGGGGAGGGdTsdT sense
    1856-1875 5335 CCCUCCCCUACAAACAGUU 5336 CCCUCCCCuAcAAAcAGUUdTsdT antis
    1860-1879 5337 GUUUGUAGGGGAGGGGAGA 5338 GuuuGuAGGGGAGGGGAGAdTsdT sense
    1860-1879 5339 UCUCCCCUCCCCUACAAAC 5340 UCUCCCCUCCCCuAcAAACdTsdT antis
    1864-1883 5341 GUAGGGGAGGGGAGAAAAG 5342 GuAGGGGAGGGGAGAAAAGdTsdT sense
    1864-1883 5343 CUUUUCUCCCCUCCCCUAC 5344 CUUUUCUCCCCUCCCCuACdTsdT antis
    1879-1898 5345 AAAGGAAGGACGGGGUUUG 5346 AAAGGAAGGAcGGGGuuuGdTsdT sense
    1879-1898 5347 CAAACCCCGUCCUUCCUUU 5348 cAAACCCCGUCCUUCCUUUdTsdT antis
    1880-1899 5349 AAGGAAGGACGGGGUUUGG 5350 AAGGAAGGAcGGGGuuuGGdTsdT sense
    1880-1899 5351 CCAAACCCCGUCCUUCCUU 5352 CcAAACCCCGUCCUUCCUUdTsdT antis
    1881-1900 5353 AGGAAGGACGGGGUUUGGG 5354 AGGAAGGAcGGGGuuuGGGdTsdT sense
    1881-1900 5355 CCCAAACCCCGUCCUUCCU 5356 CCcAAACCCCGUCCUUCCUdTsdT antis
    1906-1925 5357 AGGACCUUCUACCCCCUUG 5358 AGGAccuucuAcccccuuGdTsdT sense
    1906-1925 5359 CAAGGGGGUAGAAGGUCCU 5360 cAAGGGGGuAGAAGGUCCUdTsdT antis
    1907-1926 5361 GGACCUUCUACCCCCUUGG 5362 GGAccuucuAcccccuuGGdTsdT sense
    1907-1926 5363 CCAAGGGGGUAGAAGGUCC 5364 CcAAGGGGGuAGAAGGUCCdTsdT antis
    1908-1927 5365 GACCUUCUACCCCCUUGGU 5366 GAccuucuAcccccuuGGudTsdT sense
    1908-1927 5367 ACCAAGGGGGUAGAAGGUC 5368 ACcAAGGGGGuAGAAGGUCdTsdT antis
    1909-1928 5369 ACCUUCUACCCCCUUGGUC 5370 AccuucuAcccccuuGGucdTsdT sense
    1909-1928 5371 GACCAAGGGGGUAGAAGGU 5372 GACcAAGGGGGuAGAAGGUdTsdT antis
    1910-1929 5373 CCUUCUACCCCCUUGGUCC 5374 ccuucuAcccccuuGGuccdTsdT sense
    1910-1929 5375 GGACCAAGGGGGUAGAAGG 5376 GGACcAAGGGGGuAGAAGGdTsdT antis
    1911-1930 5377 CUUCUACCCCCUUGGUCCC 5378 cuucuAcccccuuGGucccdTsdT sense
    1911-1930 5379 GGGACCAAGGGGGUAGAAG 5380 GGGACcAAGGGGGuAGAAGdTsdT antis
    1932-1951 5381 CCCCUCCCCCAGGCUACCA 5382 ccccucccccAGGcuAccAdTsdT sense
    1932-1951 5383 UGGUAGCCUGGGGGAGGGG 5384 UGGuAGCCUGGGGGAGGGGdTsdT antis
    1942-1961 5385 AGGCUACCACUCCUUCCCU 5386 AGGcuAccAcuccuucccudTsdT sense
    1942-1961 5387 AGGGAAGGAGUGGUAGCCU 5388 AGGGAAGGAGUGGuAGCCUdTsdT antis
    1943-1962 5389 GGCUACCACUCCUUCCCUC 5390 GGcuAccAcuccuucccucdTsdT sense
    1943-1962 5391 GAGGGAAGGAGUGGUAGCC 5392 GAGGGAAGGAGUGGuAGCCdTsdT antis
    1958-1977 5393 CCUCCCCCCCUCUCCCAGG 5394 ccucccccccucucccAGGdTsdT sense
    1958-1977 5395 CCUGGGAGAGGGGGGGAGG 5396 CCUGGGAGAGGGGGGGAGGdTsdT antis
    1961-1980 5397 CCCCCCCUCUCCCAGGUCC 5398 cccccccucucccAGGuccdTsdT sense
    1961-1980 5399 GGACCUGGGAGAGGGGGGG 5400 GGACCUGGGAGAGGGGGGGdTsdT antis
    1966-1985 5401 CCUCUCCCAGGUCCCUUGU 5402 ccucucccAGGucccuuGudTsdT sense
    1966-1985 5403 ACAAGGGACCUGGGAGAGG 5404 AcAAGGGACCUGGGAGAGGdTsdT antis
    1972-1991 5405 CCAGGUCCCUUGUAAAUAG 5406 ccAGGucccuuGuAAAuAGdTsdT sense
    1972-1991 5407 CUAUUUACAAGGGACCUGG 5408 CuAUUuAcAAGGGACCUGGdTsdT antis
    1989-2008 5409 AGAACCAGCCCAGCCCAUC 5410 AGAAccAGcccAGcccAucdTsdT sense
    1989-2008 5411 GAUGGGCUGGGCUGGUUCU 5412 GAUGGGCUGGGCUGGUUCUdTsdT antis
    1990-2009 5413 GAACCAGCCCAGCCCAUCU 5414 GAAccAGcccAGcccAucudTsdT sense
    1990-2009 5415 AGAUGGGCUGGGCUGGUUC 5416 AGAUGGGCUGGGCUGGUUCdTsdT antis
    1991-2010 5417 AACCAGCCCAGCCCAUCUC 5418 AAccAGcccAGcccAucucdTsdT sense
    1991-2010 5419 GAGAUGGGCUGGGCUGGUU 5420 GAGAUGGGCUGGGCUGGUUdTsdT antis
    1992-2011 5421 ACCAGCCCAGCCCAUCUCU 5422 AccAGcccAGcccAucucudTsdT sense
    1992-2011 5423 AGAGAUGGGCUGGGCUGGU 5424 AGAGAUGGGCUGGGCUGGUdTsdT antis
    1993-2012 5425 CCAGCCCAGCCCAUCUCUC 5426 ccAGcccAGcccAucucucdTsdT sense
    1993-2012 5427 GAGAGAUGGGCUGGGCUGG 5428 GAGAGAUGGGCUGGGCUGGdTsdT antis
    2007-2026 5429 CUCUCGUCUUCCCUUCCCU 5430 cucucGucuucccuucccudTsdT sense
    2007-2026 5431 AGGGAAGGGAAGACGAGAG 5432 AGGGAAGGGAAGACGAGAGdTsdT antis
    2008-2027 5433 UCUCGUCUUCCCUUCCCUG 5434 ucucGucuucccuucccuGdTsdT sense
    2008-2027 5435 CAGGGAAGGGAAGACGAGA 5436 cAGGGAAGGGAAGACGAGAdTsdT antis
    2013-2032 5437 UCUUCCCUUCCCUGGCCCC 5438 ucuucccuucccuGGccccdTsdT sense
    2013-2032 5439 GGGGCCAGGGAAGGGAAGA 5440 GGGGCcAGGGAAGGGAAGAdTsdT antis
    2074-2033 5441 CUUCCCUUCCCUGGCCCCC 5442 cuucccuucccuGGcccccdTsdT sense
    2074-2033 5443 GGGGGCCAGGGAAGGGAAG 5444 GGGGGCcAGGGAAGGGAAGdTsdT antis
    2021-2040 5445 UCCCUGGCCCCCUGGGUGU 5446 ucccuGGcccccuGGGuGudTsdT sense
    2021-2040 5447 ACACCCAGGGGGCCAGGGA 5448 AcACCcAGGGGGCcAGGGAdTsdT antis
    2038-2057 5449 GUAAAUAGAUUGUUAUAAU 5450 GuAAAuAGAuuGuuAuAAudTsdT sense
    2038-2057 5451 AUUAUAACAAUCUAUUUAC 5452 AUuAuAAcAAUCuAUUuACdTsdT antis
    2048-2067 5453 UGUUAUAAUUUUUUCUUAA 5454 uGuuAuAAuuuuuucuuAAdTsdT sense
    2048-2067 5455 UUAAGAAAAAAUUAUAACA 5456 UuAAGAAAAAAUuAuAAcAdTsdT antis
    2106-2125 5457 GCUGUACCCCUUCUUGUCC 5458 GcuGuAccccuucuuGuccdTsdT sense
    2106-2125 5459 GGACAAGAAGGGGUACAGC 5460 GGAcAAGAAGGGGuAcAGCdTsdT antis
    2109-2128 5461 GUACCCCUUCUUGUCCUCU 5462 GuAccccuucuuGuccucudTsdT sense
    2109-2128 5463 AGAGGACAAGAAGGGGUAC 5464 AGAGGAcAAGAAGGGGuACdTsdT antis
    2120-2139 5465 UGUCCUCUGCUCCCAAGGC 5466 uGuccucuGcucccAAGGcdTsdT sense
    2120-2139 5467 GCCUUGGGAGCAGAGGACA 5468 GCCUUGGGAGcAGAGGAcAdTsdT antis
    2170-2189 5469 AGUAGAGAGAGUCCCUGGU 5470 AGuAGAGAGAGucccuGGudTsdT sense
    2170-2189 5471 ACCAGGGACUCUCUCUACU 5472 ACcAGGGACUCUCUCuACUdTsdT antis
    2180-2199 5473 GUCCCUGGUGUCUUAGUUU 5474 GucccuGGuGucuuAGuuudTsdT sense
    2180-2199 5475 AAACUAAGACACCAGGGAC 5476 AAACuAAGAcACcAGGGACdTsdT antis
    2187-2206 5477 GUGUCUUAGUUUCCACAGU 5478 GuGucuuAGuuuccAcAGudTsdT sense
    2187-2206 5479 ACUGUGGAAACUAAGACAC 5480 ACUGUGGAAACuAAGAcACdTsdT antis
    2189-2208 5481 GUCUUAGUUUCCACAGUAA 5482 GucuuAGuuuccAcAGuAAdTsdT sense
    2189-2208 5483 UUACUGUGGAAACUAAGAC 5484 UuACUGUGGAAACuAAGACdTsdT antis
    2190-2209 5485 UCUUAGUUUCCACAGUAAG 5486 ucuuAGuuuccAcAGuAAGdTsdT sense
    2190-2209 5487 CUUACUGUGGAAACUAAGA 5488 CUuACUGUGGAAACuAAGAdTsdT antis
    2225-2244 5489 ACCUCUGUUCAAUAAAUUA 5490 AccucuGuucAAuAAAuuAdTsdT sense
    2225-2244 5491 UAAUUUAUUGAACAGAGGU 5492 uAAUUuAUUGAAcAGAGGUdTsdT antis
    2238-2257 5493 AAAUUAUUGGCAUGAAACC 5494 AAAuuAuuGGcAuGAAAccdTsdT sense
    2238-2257 5495 GGUUUCAUGCCAAUAAUUU 5496 GGUUUcAUGCcAAuAAUUUdTsdT antis
    2239-2258 5497 AAUUAUUGGCAUGAAACCC 5498 AAuuAuuGGcAuGAAAcccdTsdT sense
    2239-2258 5499 GGGUUUCAUGCCAAUAAUU 5500 GGGUUUcAUGCcAAuAAUUdTsdT antis
    2241-2260 5501 UUAUUGGCAUGAAACCCUU 5502 uuAuuGGcAuGAAAcccuudTsdT sense
    2241-2260 5503 AAGGGUUUCAUGCCAAUAA 5504 AAGGGUUUcAUGCcAAuAAdTsdT antis
    34-53 5505 CAUCUCCCGGCGUGCCCCG 5506 cAucucccGGcGuGccccGdTsdT sense
    34-53 5507 CGGGGCACGCCGGGAGAUG 5508 CGGGGcACGCCGGGAGAUGdTsdT antis
    35-54 5509 AUCUCCCGGCGUGCCCCGC 5510 AucucccGGcGuGccccGcdTsdT sense
    35-54 5511 GCGGGGCACGCCGGGAGAU 5512 GCGGGGcACGCCGGGAGAUdTsdT antis
     97-116 5513 GAAGAGGCCGGAGCCCAGG 5514 GAAGAGGccGGAGcccAGGdTsdT sense
     97-116 5515 CCUGGGCUCCGGCCUCUUC 5516 CCUGGGCUCCGGCCUCUUCdTsdT antis
    163-182 5517 CCCCGCGGCCUGGGCCUGC 5518 ccccGcGGccuGGGccuGcdTsdT sense
    163-182 5519 GCAGGCCCAGGCCGCGGGG 5520 GcAGGCCcAGGCCGCGGGGdTsdT antis
    164-183 5521 CCCGCGGCCUGGGCCUGCG 5522 cccGcGGccuGGGccuGcGdTsdT sense
    164-183 5523 CGCAGGCCCAGGCCGCGGG 5524 CGcAGGCCcAGGCCGCGGGdTsdT antis
    228-247 5525 GGCUCGGGCCGGGCGCGGA 5526 GGcucGGGccGGGcGcGGAdTsdT sense
    228-247 5527 UCCGCGCCCGGCCCGAGCC 5528 UCCGCGCCCGGCCCGAGCCdTsdT antis
    235-254 5529 GCCGGGCGCGGACCAGCUC 5530 GccGGGcGcGGAccAGcucdTsdT sense
    235-254 5531 GAGCUGGUCCGCGCCCGGC 5532 GAGCUGGUCCGCGCCCGGCdTsdT antis
    247-266 5533 CCAGCUCGUUCGCGGAGCC 5534 ccAGcucGuucGcGGAGccdTsdT sense
    247-266 5535 GGCUCCGCGAACGAGCUGG 5536 GGCUCCGCGAACGAGCUGGdTsdT antis
    262-281 5537 AGCCAGGAGGCGGAGGCGG 5538 AGccAGGAGGcGGAGGcGGdTsdT sense
    262-281 5539 CCGCCUCCGCCUCCUGGCU 5540 CCGCCUCCGCCUCCUGGCUdTsdT antis
    301-320 5541 GGGGCUCGGCCUCUGGCCC 5542 GGGGcucGGccucuGGcccdTsdT sense
    301-320 5543 GGGCCAGAGGCCGAGCCCC 5544 GGGCcAGAGGCCGAGCCCCdTsdT antis
    393-412 5545 GGCCCCAGCGGCAGCGGCG 5546 GGccccAGcGGcAGcGGcGdTsdT sense
    393-412 5547 CGCCGCUGCCGCUGGGGCC 5548 CGCCGCUGCCGCUGGGGCCdTsdT antis
    403-422 5549 GCAGCGGCGGAGGAGGCAG 5550 GcAGcGGcGGAGGAGGcAGdTsdT sense
    403-422 5551 CUGCCUCCUCCGCCGCUGC 5552 CUGCCUCCUCCGCCGCUGCdTsdT antis
    420-439 5553 AGCGGUGGCCCCGGCGCGG 5554 AGcGGuGGccccGGcGcGGdTsdT sense
    420-439 5555 CCGCGCCGGGGCCACCGCU 5556 CCGCGCCGGGGCcACCGCUdTsdT antis
    502-521 5557 UAGCCACUGUAGGCCAAGG 5558 uAGccAcuGuAGGccAAGGdTsdT sense
    502-521 5559 CCUUGGCCUACAGUGGCUA 5560 CCUUGGCCuAcAGUGGCuAdTsdT antis
    531-550 5561 UCCCAAGAAGUGGCUUACA 5562 ucccAAGAAGuGGcuuAcAdTsdT sense
    531-550 5563 UGUAAGCCACUUCUUGGGA 5564 UGuAAGCcACUUCUUGGGAdTsdT antis
    665-684 5565 CCGAGAACUGCAGAUUAUG 5566 ccGAGAAcuGcAGAuuAuGdTsdT sense
    665-684 5567 CAUAAUCUGCAGUUCUCGG 5568 cAuAAUCUGcAGUUCUCGGdTsdT antis
    1148-1167 5569 CUUCCCUGGGGACAGUGGG 5570 cuucccuGGGGAcAGuGGGdTsdT sense
    1148-1167 5571 CCCACUGUCCCCAGGGAAG 5572 CCcACUGUCCCcAGGGAAGdTsdT antis
    1356-1375 5573 CCAUCCUCAAGGCUCUCCC 5574 ccAuccucAAGGcucucccdTsdT sense
    1356-1375 5575 GGGAGAGCCUUGAGGAUGG 5576 GGGAGAGCCUUGAGGAUGGdTsdT antis
    1358-1377 5577 AUCCUCAAGGCUCUCCCCA 5578 AuccucAAGGcucuccccAdTsdT sense
    1358-1377 5579 UGGGGAGAGCCUUGAGGAU 5580 UGGGGAGAGCCUUGAGGAUdTsdT antis
    1485-1504 5581 UCCAUCCAACCAUCUCUCA 5582 uccAuccAAccAucucucAdTsdT sense
    1485-1504 5583 UGAGAGAUGGUUGGAUGGA 5584 UGAGAGAUGGUUGGAUGGAdTsdT antis
    1620-1639 5585 CAGCCAUCUGAUGCCACAA 5586 cAGccAucuGAuGccAcAAdTsdT sense
    1620-1639 5587 UUGUGGCAUCAGAUGGCUG 5588 UUGUGGcAUcAGAUGGCUGdTsdT antis
    1813-1832 5589 UCAGCAGCCUAACCUCUGU 5590 ucAGcAGccuAAccucuGudTsdT sense
    1813-1832 5591 ACAGAGGUUAGGCUGCUGA 5592 AcAGAGGUuAGGCUGCUGAdTsdT antis
    1954-1973 5593 CUUCCCUCCCCCCCUCUCC 5594 cuucccucccccccucuccdTsdT sense
    1954-1973 5595 GGAGAGGGGGGGAGGGAAG 5596 GGAGAGGGGGGGAGGGAAGdTsdT antis
    1957-1976 5597 CCCUCCCCCCCUCUCCCAG 5598 cccucccccccucucccAGdTsdT sense
    1957-1976 5599 CUGGGAGAGGGGGGGAGGG 5600 CUGGGAGAGGGGGGGAGGGdTsdT antis
    2103-2122 5601 CCAGCUGUACCCCUUCUUG 5602 ccAGcuGuAccccuucuuGdTsdT sense
    2103-2122 5603 CAAGAAGGGGUACAGCUGG 5604 cAAGAAGGGGuAcAGCUGGdTsdT antis
    2119-2138 5605 UUGUCCUCUGCUCCCAAGG 5606 uuGuccucuGcucccAAGGdTsdT sense
    2119-2138 5607 CCUUGGGAGCAGAGGACAA 5608 CCUUGGGAGcAGAGGAcAAdTsdT antis
    2122-2141 5609 UCCUCUGCUCCCAAGGCUU 5610 uccucuGcucccAAGGcuudTsdT sense
    2122-2141 5611 AAGCCUUGGGAGCAGAGGA 5612 AAGCCUUGGGAGcAGAGGAdTsdT antis
    2125-2144 5613 UCUGCUCCCAAGGCUUCCU 5614 ucuGcucccAAGGcuuccudTsdT sense
    2125-2144 5615 AGGAAGCCUUGGGAGCAGA 5616 AGGAAGCCUUGGGAGcAGAdTsdT antis
    2154-2173 5617 AUCCUGGAAGGAGGGGAGU 5618 AuccuGGAAGGAGGGGAGudTsdT sense
    2154-2173 5619 ACUCCCCUCCUUCCAGGAU 5620 ACUCCCCUCCUUCcAGGAUdTsdT antis
    33-52 5621 UCAUCUCCCGGCGUGCCCC 5622 ucAucucccGGcGuGccccdTsdT sense
    33-52 5623 GGGGCACGCCGGGAGAUGA 5624 GGGGcACGCCGGGAGAUGAdTsdT antis
    46-65 5625 UGCCCCGCGGCGGGCGCUG 5626 uGccccGcGGcGGGcGcuGdTsdT sense
    46-65 5627 CAGCGCCCGCCGCGGGGCA 5628 cAGCGCCCGCCGCGGGGcAdTsdT antis
    47-66 5629 GCCCCGCGGCGGGCGCUGG 5630 GccccGcGGcGGGcGcuGGdTsdT sense
    47-66 5631 CCAGCGCCCGCCGCGGGGC 5632 CcAGCGCCCGCCGCGGGGCdTsdT antis
    53-72 5633 CGGCGGGCGCUGGGCCGGA 5634 cGGcGGGcGcuGGGccGGAdTsdT sense
    53-72 5635 UCCGGCCCAGCGCCCGCCG 5636 UCCGGCCcAGCGCCCGCCGdTsdT antis
    54-73 5637 GGCGGGCGCUGGGCCGGAG 5638 GGcGGGcGcuGGGccGGAGdTsdT sense
    54-73 5639 CUCCGGCCCAGCGCCCGCC 5640 CUCCGGCCcAGCGCCCGCCdTsdT antis
    55-74 5641 GCGGGCGCUGGGCCGGAGC 5642 GcGGGcGcuGGGccGGAGcdTsdT sense
    55-74 5643 GCUCCGGCCCAGCGCCCGC 5644 GCUCCGGCCcAGCGCCCGCdTsdT antis
    61-80 5645 GCUGGGCCGGAGCCGGAGC 5646 GcuGGGccGGAGccGGAGcdTsdT sense
    61-80 5647 GCUCCGGCUCCGGCCCAGC 5648 GCUCCGGCUCCGGCCcAGCdTsdT antis
    64-83 5649 GGGCCGGAGCCGGAGCCCG 5650 GGGccGGAGccGGAGcccGdTsdT sense
    64-83 5651 CGGGCUCCGGCUCCGGCCC 5652 CGGGCUCCGGCUCCGGCCCdTsdT antis
    67-86 5653 CCGGAGCCGGAGCCCGAAC 5654 ccGGAGccGGAGcccGAAcdTsdT sense
    67-86 5655 GUUCGGGCUCCGGCUCCGG 5656 GUUCGGGCUCCGGCUCCGGdTsdT antis
     92-111 5657 GCCUGGAAGAGGCCGGAGC 5658 GccuGGAAGAGGccGGAGcdTsdT sense
     92-111 5659 GCUCCGGCCUCUUCCAGGC 5660 GCUCCGGCCUCUUCcAGGCdTsdT antis
     93-112 5661 CCUGGAAGAGGCCGGAGCC 5662 ccuGGAAGAGGccGGAGccdTsdT sense
     93-112 5663 GGCUCCGGCCUCUUCCAGG 5664 GGCUCCGGCCUCUUCcAGGdTsdT antis
    101-120 5665 AGGCCGGAGCCCAGGGGAG 5666 AGGccGGAGcccAGGGGAGdTsdT sense
    101-120 5667 CUCCCCUGGGCUCCGGCCU 5668 CUCCCCUGGGCUCCGGCCUdTsdT antis
    102-121 5669 GGCCGGAGCCCAGGGGAGG 5670 GGccGGAGcccAGGGGAGGdTsdT sense
    102-121 5671 CCUCCCCUGGGCUCCGGCC 5672 CCUCCCCUGGGCUCCGGCCdTsdT antis
    106-125 5673 GGAGCCCAGGGGAGGCGGC 5674 GGAGcccAGGGGAGGcGGcdTsdT sense
    106-125 5675 GCCGCCUCCCCUGGGCUCC 5676 GCCGCCUCCCCUGGGCUCCdTsdT antis
    110-129 5677 CCCAGGGGAGGCGGCGGCA 5678 cccAGGGGAGGcGGcGGcAdTsdT sense
    110-129 5679 UGCCGCCGCCUCCCCUGGG 5680 UGCCGCCGCCUCCCCUGGGdTsdT antis
    111-130 5681 CCAGGGGAGGCGGCGGCAG 5682 ccAGGGGAGGcGGcGGcAGdTsdT sense
    111-130 5683 CUGCCGCCGCCUCCCCUGG 5684 CUGCCGCCGCCUCCCCUGGdTsdT antis
    122-141 5685 GGCGGCAGAGGCAGCGGCG 5686 GGcGGcAGAGGcAGcGGcGdTsdT sense
    122-141 5687 CGCCGCUGCCUCUGCCGCC 5688 CGCCGCUGCCUCUGCCGCCdTsdT antis
    123-142 5689 GCGGCAGAGGCAGCGGCGG 5690 GcGGcAGAGGcAGcGGcGGdTsdT sense
    123-142 5691 CCGCCGCUGCCUCUGCCGC 5692 CCGCCGCUGCCUCUGCCGCdTsdT antis
    124-143 5693 CGGCAGAGGCAGCGGCGGG 5694 cGGcAGAGGcAGcGGcGGGdTsdT sense
    124-143 5695 CCCGCCGCUGCCUCUGCCG 5696 CCCGCCGCUGCCUCUGCCGdTsdT antis
    125-144 5697 GGCAGAGGCAGCGGCGGGG 5698 GGcAGAGGcAGcGGcGGGGdTsdT sense
    125-144 5699 CCCCGCCGCUGCCUCUGCC 5700 CCCCGCCGCUGCCUCUGCCdTsdT antis
    132-151 5701 GCAGCGGCGGGGGCAGCCC 5702 GcAGcGGcGGGGGcAGcccdTsdT sense
    132-151 5703 GGGCUGCCCCCGCCGCUGC 5704 GGGCUGCCCCCGCCGCUGCdTsdT antis
    139-158 5705 CGGGGGCAGCCCAGGCAGC 5706 cGGGGGcAGcccAGGcAGcdTsdT sense
    139-158 5707 GCUGCCUGGGCUGCCCCCG 5708 GCUGCCUGGGCUGCCCCCGdTsdT antis
    143-162 5709 GGCAGCCCAGGCAGCCCGA 5710 GGcAGcccAGGcAGcccGAdTsdT sense
    143-162 5711 UCGGGCUGCCUGGGCUGCC 5712 UCGGGCUGCCUGGGCUGCCdTsdT antis
    146-165 5713 AGCCCAGGCAGCCCGAGCC 5714 AGcccAGGcAGcccGAGccdTsdT sense
    146-165 5715 GGCUCGGGCUGCCUGGGCU 5716 GGCUCGGGCUGCCUGGGCUdTsdT antis
    152-171 5717 GGCAGCCCGAGCCCCGCGG 5718 GGcAGcccGAGccccGcGGdTsdT sense
    152-171 5719 CCGCGGGGCUCGGGCUGCC 5720 CCGCGGGGCUCGGGCUGCCdTsdT antis
    154-173 5721 CAGCCCGAGCCCCGCGGCC 5722 cAGcccGAGccccGcGGccdTsdT sense
    154-173 5723 GGCCGCGGGGCUCGGGCUG 5724 GGCCGCGGGGCUCGGGCUGdTsdT antis
    155-174 5725 AGCCCGAGCCCCGCGGCCU 5726 AGcccGAGccccGcGGccudTsdT sense
    155-174 5727 AGGCCGCGGGGCUCGGGCU 5728 AGGCCGCGGGGCUCGGGCUdTsdT antis
    156-175 5729 GCCCGAGCCCCGCGGCCUG 5730 GcccGAGccccGcGGccuGdTsdT sense
    156-175 5731 CAGGCCGCGGGGCUCGGGC 5732 cAGGCCGCGGGGCUCGGGCdTsdT antis
    159-178 5733 CGAGCCCCGCGGCCUGGGC 5734 cGAGccccGcGGccuGGGcdTsdT sense
    159-178 5735 GCCCAGGCCGCGGGGCUCG 5736 GCCcAGGCCGCGGGGCUCGdTsdT antis
    160-179 5737 GAGCCCCGCGGCCUGGGCC 5738 GAGccccGcGGccuGGGccdTsdT sense
    160-179 5739 GGCCCAGGCCGCGGGGCUC 5740 GGCCcAGGCCGCGGGGCUCdTsdT antis
    161-180 5741 AGCCCCGCGGCCUGGGCCU 5742 AGccccGcGGccuGGGccudTsdT sense
    161-180 5743 AGGCCCAGGCCGCGGGGCU 5744 AGGCCcAGGCCGCGGGGCUdTsdT antis
    162-181 5745 GCCCCGCGGCCUGGGCCUG 5746 GccccGcGGccuGGGccuGdTsdT sense
    162-181 5747 CAGGCCCAGGCCGCGGGGC 5748 cAGGCCcAGGCCGCGGGGCdTsdT antis
    174-193 5749 GGGCCUGCGCUCGGCGCCA 5750 GGGccuGcGcucGGcGccAdTsdT sense
    174-193 5751 UGGCGCCGAGCGCAGGCCC 5752 UGGCGCCGAGCGcAGGCCCdTsdT antis
    210-229 5753 UCGGGAGGCGGCCCUGGGG 5754 ucGGGAGGcGGcccuGGGGdTsdT sense
    210-229 5755 CCCCAGGGCCGCCUCCCGA 5756 CCCcAGGGCCGCCUCCCGAdTsdT antis
    211-230 5757 CGGGAGGCGGCCCUGGGGG 5758 cGGGAGGcGGcccuGGGGGdTsdT sense
    211-230 5759 CCCCCAGGGCCGCCUCCCG 5760 CCCCcAGGGCCGCCUCCCGdTsdT antis
    212-231 5761 GGGAGGCGGCCCUGGGGGC 5762 GGGAGGcGGcccuGGGGGcdTsdT sense
    212-231 5763 GCCCCCAGGGCCGCCUCCC 5764 GCCCCcAGGGCCGCCUCCCdTsdT antis
    217-236 5765 GCGGCCCUGGGGGCUCGGG 5766 GcGGcccuGGGGGcucGGGdTsdT sense
    217-236 5767 CCCGAGCCCCCAGGGCCGC 5768 CCCGAGCCCCcAGGGCCGCdTsdT antis
    218-237 5769 CGGCCCUGGGGGCUCGGGC 5770 cGGcccuGGGGGcucGGGcdTsdT sense
    218-237 5771 GCCCGAGCCCCCAGGGCCG 5772 GCCCGAGCCCCcAGGGCCGdTsdT antis
    225-244 5773 GGGGGCUCGGGCCGGGCGC 5774 GGGGGcucGGGccGGGcGcdTsdT sense
    225-244 5775 GCGCCCGGCCCGAGCCCCC 5776 GCGCCCGGCCCGAGCCCCCdTsdT antis
    226-245 5777 GGGGCUCGGGCCGGGCGCG 5778 GGGGcucGGGccGGGcGcGdTsdT sense
    226-245 5779 CGCGCCCGGCCCGAGCCCC 5780 CGCGCCCGGCCCGAGCCCCdTsdT antis
    232-251 5781 CGGGCCGGGCGCGGACCAG 5782 cGGGccGGGcGcGGAccAGdTsdT sense
    232-251 5783 CUGGUCCGCGCCCGGCCCG 5784 CUGGUCCGCGCCCGGCCCGdTsdT antis
    260-279 5785 GGAGCCAGGAGGCGGAGGC 5786 GGAGccAGGAGGcGGAGGcdTsdT sense
    260-279 5787 GCCUCCGCCUCCUGGCUCC 5788 GCCUCCGCCUCCUGGCUCCdTsdT antis
    263-282 5789 GCCAGGAGGCGGAGGCGGA 5790 GccAGGAGGcGGAGGcGGAdTsdT sense
    263-282 5791 UCCGCCUCCGCCUCCUGGC 5792 UCCGCCUCCGCCUCCUGGCdTsdT antis
    264-283 5793 CCAGGAGGCGGAGGCGGAG 5794 ccAGGAGGcGGAGGcGGAGdTsdT sense
    264-283 5795 CUCCGCCUCCGCCUCCUGG 5796 CUCCGCCUCCGCCUCCUGGdTsdT antis
    270-289 5797 GGCGGAGGCGGAGGUGGUG 5798 GGcGGAGGcGGAGGuGGuGdTsdT sense
    270-289 5799 CACCACCUCCGCCUCCGCC 5800 cACcACCUCCGCCUCCGCCdTsdT antis
    280-299 5801 GAGGUGGUGGCGGCGGCCC 5802 GAGGuGGuGGcGGcGGcccdTsdT sense
    280-299 5803 GGGCCGCCGCCACCACCUC 5804 GGGCCGCCGCcACcACCUCdTsdT antis
    281-300 5805 AGGUGGUGGCGGCGGCCCC 5806 AGGuGGuGGcGGcGGccccdTsdT sense
    281-300 5807 GGGGCCGCCGCCACCACCU 5808 GGGGCCGCCGCcACcACCUdTsdT antis
    282-301 5809 GGUGGUGGCGGCGGCCCCG 5810 GGuGGuGGcGGcGGccccGdTsdT sense
    282-301 5811 CGGGGCCGCCGCCACCACC 5812 CGGGGCCGCCGCcACcACCdTsdT antis
    283-302 5813 GUGGUGGCGGCGGCCCCGG 5814 GuGGuGGcGGcGGccccGGdTsdT sense
    283-302 5815 CCGGGGCCGCCGCCACCAC 5816 CCGGGGCCGCCGCcACcACdTsdT antis
    289-308 5817 GCGGCGGCCCCGGGGGCUC 5818 GcGGcGGccccGGGGGcucdTsdT sense
    289-308 5819 GAGCCCCCGGGGCCGCCGC 5820 GAGCCCCCGGGGCCGCCGCdTsdT antis
    291-310 5821 GGCGGCCCCGGGGGCUCGG 5822 GGcGGccccGGGGGcucGGdTsdT sense
    291-310 5823 CCGAGCCCCCGGGGCCGCC 5824 CCGAGCCCCCGGGGCCGCCdTsdT antis
    296-315 5825 CCCCGGGGGCUCGGCCUCU 5826 ccccGGGGGcucGGccucudTsdT sense
    296-315 5827 AGAGGCCGAGCCCCCGGGG 5828 AGAGGCCGAGCCCCCGGGGdTsdT antis
    303-322 5829 GGCUCGGCCUCUGGCCCAG 5830 GGcucGGccucuGGcccAGdTsdT sense
    303-322 5831 CUGGGCCAGAGGCCGAGCC 5832 CUGGGCcAGAGGCCGAGCCdTsdT antis
    320-339 5833 AGGAGGCACUGGCGGCGGG 5834 AGGAGGcAcuGGcGGcGGGdTsdT sense
    320-339 5835 CCCGCCGCCAGUGCCUCCU 5836 CCCGCCGCcAGUGCCUCCUdTsdT antis
    382-401 5837 GCUCCGGGGGUGGCCCCAG 5838 GcuccGGGGGuGGccccAGdTsdT sense
    382-401 5839 CUGGGGCCACCCCCGGAGC 5840 CUGGGGCcACCCCCGGAGCdTsdT antis
    383-402 5841 CUCCGGGGGUGGCCCCAGC 5842 cuccGGGGGuGGccccAGcdTsdT sense
    383-402 5843 GCUGGGGCCACCCCCGGAG 5844 GCUGGGGCcACCCCCGGAGdTsdT antis
    395-414 5845 CCCCAGCGGCAGCGGCGGA 5846 ccccAGcGGcAGcGGcGGAdTsdT sense
    395-414 5847 UCCGCCGCUGCCGCUGGGG 5848 UCCGCCGCUGCCGCUGGGGdTsdT antis
    396-415 5849 CCCAGCGGCAGCGGCGGAG 5850 cccAGcGGcAGcGGcGGAGdTsdT sense
    396-415 5851 CUCCGCCGCUGCCGCUGGG 5852 CUCCGCCGCUGCCGCUGGGdTsdT antis
    397-416 5853 CCAGCGGCAGCGGCGGAGG 5854 ccAGcGGcAGcGGcGGAGGdTsdT sense
    397-416 5855 CCUCCGCCGCUGCCGCUGG 5856 CCUCCGCCGCUGCCGCUGGdTsdT antis
    398-417 5857 CAGCGGCAGCGGCGGAGGA 5858 cAGcGGcAGcGGcGGAGGAdTsdT sense
    398-417 5859 UCCUCCGCCGCUGCCGCUG 5860 UCCUCCGCCGCUGCCGCUGdTsdT antis
    400-419 5861 GCGGCAGCGGCGGAGGAGG 5862 GcGGcAGcGGcGGAGGAGGdTsdT sense
    400-419 5863 CCUCCUCCGCCGCUGCCGC 5864 CCUCCUCCGCCGCUGCCGCdTsdT antis
    405-424 5865 AGCGGCGGAGGAGGCAGCG 5866 AGcGGcGGAGGAGGcAGcGdTsdT sense
    405-424 5867 CGCUGCCUCCUCCGCCGCU 5868 CGCUGCCUCCUCCGCCGCUdTsdT antis
    406-425 5869 GCGGCGGAGGAGGCAGCGG 5870 GcGGcGGAGGAGGcAGcGGdTsdT sense
    406-425 5871 CCGCUGCCUCCUCCGCCGC 5872 CCGCUGCCUCCUCCGCCGCdTsdT antis
    407-426 5873 CGGCGGAGGAGGCAGCGGU 5874 cGGcGGAGGAGGcAGcGGudTsdT sense
    407-426 5875 ACCGCUGCCUCCUCCGCCG 5876 ACCGCUGCCUCCUCCGCCGdTsdT antis
    408-427 5877 GGCGGAGGAGGCAGCGGUG 5878 GGcGGAGGAGGcAGcGGuGdTsdT sense
    408-427 5879 CACCGCUGCCUCCUCCGCC 5880 cACCGCUGCCUCCUCCGCCdTsdT antis
    444-463 5881 AGCUUCCCGCCGCCGGGAG 5882 AGcuucccGccGccGGGAGdTsdT sense
    444-463 5883 CUCCCGGCGGCGGGAAGCU 5884 CUCCCGGCGGCGGGAAGCUdTsdT antis
    461-480 5885 AGUGAAGCUGGGCCGUGAC 5886 AGuGAAGcuGGGccGuGAcdTsdT sense
    461-480 5887 GUCACGGCCCAGCUUCACU 5888 GUcACGGCCcAGCUUcACUdTsdT antis
    493-512 5889 CCACAGUGGUAGCCACUGU 5890 ccAcAGuGGuAGccAcuGudTsdT sense
    493-512 5891 ACAGUGGCUACCACUGUGG 5892 AcAGUGGCuACcACUGUGGdTsdT antis
    513-532 5893 GGCCAAGGCCCAGAGCGUU 5894 GGccAAGGcccAGAGcGuudTsdT sense
    513-532 5895 AACGCUCUGGGCCUUGGCC 5896 AACGCUCUGGGCCUUGGCCdTsdT antis
    606-625 5897 GCAGAGACGAGGGAACUGG 5898 GcAGAGAcGAGGGAAcuGGdTsdT sense
    606-625 5899 CCAGUUCCCUCGUCUCUGC 5900 CcAGUUCCCUCGUCUCUGCdTsdT antis
    616-635 5901 GGGAACUGGUGGCCAUCAA 5902 GGGAAcuGGuGGccAucAAdTsdT sense
    616-635 5903 UUGAUGGCCACCAGUUCCC 5904 UUGAUGGCcACcAGUUCCCdTsdT antis
    620-639 5905 ACUGGUGGCCAUCAAGAAG 5906 AcuGGuGGccAucAAGAAGdTsdT sense
    620-639 5907 CUUCUUGAUGGCCACCAGU 5908 CUUCUUGAUGGCcACcAGUdTsdT antis
    621-640 5909 CUGGUGGCCAUCAAGAAGG 5910 cuGGuGGccAucAAGAAGGdTsdT sense
    621-640 5911 CCUUCUUGAUGGCCACCAG 5912 CCUUCUUGAUGGCcACcAGdTsdT antis
    711-730 5913 AGGCUGCGGUACUUUUUCU 5914 AGGcuGcGGuAcuuuuucudTsdT sense
    711-730 5915 AGAAAAAGUACCGCAGCCU 5916 AGAAAAAGuACCGcAGCCUdTsdT antis
    712-731 5917 GGCUGCGGUACUUUUUCUA 5918 GGcuGcGGuAcuuuuucuAdTsdT sense
    712-731 5919 UAGAAAAAGUACCGCAGCC 5920 uAGAAAAAGuACCGcAGCCdTsdT antis
    716-735 5921 GCGGUACUUUUUCUACUCC 5922 GcGGuAcuuuuucuAcuccdTsdT sense
    716-735 5923 GGAGUAGAAAAAGUACCGC 5924 GGAGuAGAAAAAGuACCGCdTsdT antis
    851-870 5925 CAUCAAGGUGUACAUGUAC 5926 cAucAAGGuGuAcAuGuAcdTsdT sense
    851-870 5927 GUACAUGUACACCUUGAUG 5928 GuAcAUGuAcACCUUGAUGdTsdT antis
    891-910 5929 UACAUCCACUCCCAAGGUG 5930 uAcAuccAcucccAAGGuGdTsdT sense
    891-910 5931 CACCUUGGGAGUGGAUGUA 5932 cACCUUGGGAGUGGAUGuAdTsdT antis
    948-967 5933 GACCCUGACACUGCUGUCC 5934 GAcccuGAcAcuGcuGuccdTsdT sense
    948-967 5935 GGACAGCAGUGUCAGGGUC 5936 GGAcAGcAGUGUcAGGGUCdTsdT antis
    951-970 5937 CCUGACACUGCUGUCCUCA 5938 ccuGAcAcuGcuGuccucAdTsdT sense
    951-970 5939 UGAGGACAGCAGUGUCAGG 5940 UGAGGAcAGcAGUGUcAGGdTsdT antis
    955-974 5941 ACACUGCUGUCCUCAAGCU 5942 AcAcuGcuGuccucAAGcudTsdT sense
    955-974 5943 AGCUUGAGGACAGCAGUGU 5944 AGCUUGAGGAcAGcAGUGUdTsdT antis
    956-975 5945 CACUGCUGUCCUCAAGCUC 5946 cAcuGcuGuccucAAGcucdTsdT sense
    956-975 5947 GAGCUUGAGGACAGCAGUG 5948 GAGCUUGAGGAcAGcAGUGdTsdT antis
    958-977 5949 CUGCUGUCCUCAAGCUCUG 5950 cuGcuGuccucAAGcucuGdTsdT sense
    958-977 5951 CAGAGCUUGAGGACAGCAG 5952 cAGAGCUUGAGGAcAGcAGdTsdT antis
    959-978 5953 UGCUGUCCUCAAGCUCUGC 5954 uGcuGuccucAAGcucuGcdTsdT sense
    959-978 5955 GCAGAGCUUGAGGACAGCA 5956 GcAGAGCUUGAGGAcAGcAdTsdT antis
    1028-1047 5957 CAUCUGCUCUCGGUACUAC 5958 cAucuGcucucGGuAcuAcdTsdT sense
    1028-1047 5959 GUAGUACCGAGAGCAGAUG 5960 GuAGuACCGAGAGcAGAUGdTsdT antis
    1052-1071 5961 UCCAGAACUCAUCUUUGGA 5962 uccAGAAcucAucuuuGGAdTsdT sense
    1052-1071 5963 UCCAAAGAUGAGUUCUGGA 5964 UCcAAAGAUGAGUUCUGGAdTsdT antis
    1084-1103 5965 CCUCGUCCAUCGAUGUGUG 5966 ccucGuccAucGAuGuGuGdTsdT sense
    1084-1103 5967 CACACAUCGAUGGACGAGG 5968 cAcAcAUCGAUGGACGAGGdTsdT antis
    1103-1122 5969 GUCGGCUGGCUGUGUACUU 5970 GucGGcuGGcuGuGuAcuudTsdT sense
    1103-1122 5971 AAGUACACAGCCAGCCGAC 5972 AAGuAcAcAGCcAGCCGACdTsdT antis
    1111-1130 5973 GCUGUGUACUUGCUGAGCU 5974 GcuGuGuAcuuGcuGAGcudTsdT sense
    1111-1130 5975 AGCUCAGCAAGUACACAGC 5976 AGCUcAGcAAGuAcAcAGCdTsdT antis
    1116-1135 5977 GUACUUGCUGAGCUACUUC 5978 GuAcuuGcuGAGcuAcuucdTsdT sense
    1116-1135 5979 GAAGUAGCUCAGCAAGUAC 5980 GAAGuAGCUcAGcAAGuACdTsdT antis
    1132-1151 5981 UUCUCGGCCAGCCCAUCUU 5982 uucucGGccAGcccAucuudTsdT sense
    1132-1151 5983 AAGAUGGGCUGGCCGAGAA 5984 AAGAUGGGCUGGCCGAGAAdTsdT antis
    1133-1152 5985 UCUCGGCCAGCCCAUCUUC 5986 ucucGGccAGcccAucuucdTsdT sense
    1133-1152 5987 GAAGAUGGGCUGGCCGAGA 5988 GAAGAUGGGCUGGCCGAGAdTsdT antis
    1136-1155 5989 CGGCCAGCCCAUCUUCCCU 5990 cGGccAGcccAucuucccudTsdT sense
    1136-1155 5991 AGGGAAGAUGGGCUGGCCG 5992 AGGGAAGAUGGGCUGGCCGdTsdT antis
    1143-1162 5993 CCCAUCUUCCCUGGGGACA 5994 cccAucuucccuGGGGAcAdTsdT sense
    1143-1162 5995 UGUCCCCAGGGAAGAUGGG 5996 UGUCCCcAGGGAAGAUGGGdTsdT antis
    1147-1166 5997 UCUUCCCUGGGGACAGUGG 5998 ucuucccuGGGGAcAGuGGdTsdT sense
    1147-1166 5999 CCACUGUCCCCAGGGAAGA 6000 CcACUGUCCCcAGGGAAGAdTsdT antis
    1152-1171 6001 CCUGGGGACAGUGGGGUGG 6002 ccuGGGGAcAGuGGGGuGGdTsdT sense
    1152-1171 6003 CCACCCCACUGUCCCCAGG 6004 CcACCCcACUGUCCCcAGGdTsdT antis
    1161-1180 6005 AGUGGGGUGGACCAGCUUG 6006 AGuGGGGuGGAccAGcuuGdTsdT sense
    1161-1180 6007 CAAGCUGGUCCACCCCACU 6008 cAAGCUGGUCcACCCcACUdTsdT antis
    1277-1296 6009 CCCUUGGACAAAGGUGUUC 6010 cccuuGGAcAAAGGuGuucdTsdT sense
    1277-1296 6011 GAACACCUUUGUCCAAGGG 6012 GAAcACCUUUGUCcAAGGGdTsdT antis
    1298-1317 6013 AUCUUCAAAGACACCACCU 6014 AucuucAAAGAcAccAccudTsdT sense
    1298-1317 6015 AGGUGGUGUCUUUGAAGAU 6016 AGGUGGUGUCUUUGAAGAUdTsdT antis
    1300-1319 6017 CUUCAAAGACACCACCUGA 6018 cuucAAAGAcAccAccuGAdTsdT sense
    1300-1319 6019 UCAGGUGGUGUCUUUGAAG 6020 UcAGGUGGUGUCUUUGAAGdTsdT antis
    1301-1320 6021 UUCAAAGACACCACCUGAG 6022 uucAAAGAcAccAccuGAGdTsdT sense
    1301-1320 6023 CUCAGGUGGUGUCUUUGAA 6024 CUcAGGUGGUGUCUUUGAAdTsdT antis
    1357-1376 6025 CAUCCUCAAGGCUCUCCCC 6026 cAuccucAAGGcucuccccdTsdT sense
    1357-1376 6027 GGGGAGAGCCUUGAGGAUG 6028 GGGGAGAGCCUUGAGGAUGdTsdT antis
    1390-1409 6029 CCCACAGCUUCUUCGAUGA 6030 cccAcAGcuucuucGAuGAdTsdT sense
    1390-1409 6031 UCAUCGAAGAAGCUGUGGG 6032 UcAUCGAAGAAGCUGUGGGdTsdT antis
    1419-1438 6033 CUCGGAGCCCAGCUCCCCA 6034 cucGGAGcccAGcuccccAdTsdT sense
    1419-1438 6035 UGGGGAGCUGGGCUCCGAG 6036 UGGGGAGCUGGGCUCCGAGdTsdT antis
    1421-1440 6037 CGGAGCCCAGCUCCCCAAC 6038 cGGAGcccAGcuccccAAcdTsdT sense
    1421-1440 6039 GUUGGGGAGCUGGGCUCCG 6040 GUUGGGGAGCUGGGCUCCGdTsdT antis
    1497-1516 6041 UCUCUCAAUGCCAUUCUCA 6042 ucucucAAuGccAuucucAdTsdT sense
    1497-1516 6043 UGAGAAUGGCAUUGAGAGA 6044 UGAGAAUGGcAUUGAGAGAdTsdT antis
    1500-1519 6045 CUCAAUGCCAUUCUCAUCC 6046 cucAAuGccAuucucAuccdTsdT sense
    1500-1519 6047 GGAUGAGAAUGGCAUUGAG 6048 GGAUGAGAAUGGcAUUGAGdTsdT antis
    1501-1520 6049 UCAAUGCCAUUCUCAUCCC 6050 ucAAuGccAuucucAucccdTsdT sense
    1501-1520 6051 GGGAUGAGAAUGGCAUUGA 6052 GGGAUGAGAAUGGcAUUGAdTsdT antis
    1540-1559 6053 CAGGCCCUGCUUCUCCCCU 6054 cAGGcccuGcuucuccccudTsdT sense
    1540-1559 6055 AGGGGAGAAGCAGGGCCUG 6056 AGGGGAGAAGcAGGGCCUGdTsdT antis
    1547-1566 6057 UGCUUCUCCCCUCACCACU 6058 uGcuucuccccucAccAcudTsdT sense
    1547-1566 6059 AGUGGUGAGGGGAGAAGCA 6060 AGUGGUGAGGGGAGAAGcAdTsdT antis
    1586-1605 6061 AGCUUUAACUGAAGCUCAG 6062 AGcuuuAAcuGAAGcucAGdTsdT sense
    1586-1605 6063 CUGAGCUUCAGUUAAAGCU 6064 CUGAGCUUcAGUuAAAGCUdTsdT antis
    1621-1640 6065 AGCCAUCUGAUGCCACAAC 6066 AGccAucuGAuGccAcAAcdTsdT sense
    1621-1640 6067 GUUGUGGCAUCAGAUGGCU 6068 GUUGUGGcAUcAGAUGGCUdTsdT antis
    1818-1837 6069 AGCCUAACCUCUGUGGUGG 6070 AGccuAAccucuGuGGuGGdTsdT sense
    1818-1837 6071 CCACCACAGAGGUUAGGCU 6072 CcACcAcAGAGGUuAGGCUdTsdT antis
    1865-1884 6073 UAGGGGAGGGGAGAAAAGG 6074 uAGGGGAGGGGAGAAAAGGdTsdT sense
    1865-1884 6075 CCUUUUCUCCCCUCCCCUA 6076 CCUUUUCUCCCCUCCCCuAdTsdT antis
    1866-1885 6077 AGGGGAGGGGAGAAAAGGA 6078 AGGGGAGGGGAGAAAAGGAdTsdT sense
    1866-1885 6079 UCCUUUUCUCCCCUCCCCU 6080 UCCUUUUCUCCCCUCCCCUdTsdT antis
    1867-1886 6081 GGGGAGGGGAGAAAAGGAA 6082 GGGGAGGGGAGAAAAGGAAdTsdT sense
    1867-1886 6083 UUCCUUUUCUCCCCUCCCC 6084 UUCCUUUUCUCCCCUCCCCdTsdT antis
    1868-1887 6085 GGGAGGGGAGAAAAGGAAG 6086 GGGAGGGGAGAAAAGGAAGdTsdT sense
    1868-1887 6087 CUUCCUUUUCUCCCCUCCC 6088 CUUCCUUUUCUCCCCUCCCdTsdT antis
    1872-1891 6089 GGGGAGAAAAGGAAGGACG 6090 GGGGAGAAAAGGAAGGAcGdTsdT sense
    1872-1891 6091 CGUCCUUCCUUUUCUCCCC 6092 CGUCCUUCCUUUUCUCCCCdTsdT antis
    1901-1920 6093 GUGUGAGGACCUUCUACCC 6094 GuGuGAGGAccuucuAcccdTsdT sense
    1901-1920 6095 GGGUAGAAGGUCCUCACAC 6096 GGGuAGAAGGUCCUcAcACdTsdT antis
    1929-1948 6097 CCUCCCCUCCCCCAGGCUA 6098 ccuccccucccccAGGcuAdTsdT sense
    1929-1948 6099 UAGCCUGGGGGAGGGGAGG 6100 uAGCCUGGGGGAGGGGAGGdTsdT antis
    1930-1949 6101 CUCCCCUCCCCCAGGCUAC 6102 cuccccucccccAGGcuAcdTsdT sense
    1930-1949 6103 GUAGCCUGGGGGAGGGGAG 6104 GuAGCCUGGGGGAGGGGAGdTsdT antis
    1947-1966 6105 ACCACUCCUUCCCUCCCCC 6106 AccAcuccuucccucccccdTsdT sense
    1947-1966 6107 GGGGGAGGGAAGGAGUGGU 6108 GGGGGAGGGAAGGAGUGGUdTsdT antis
    1948-1967 6109 CCACUCCUUCCCUCCCCCC 6110 ccAcuccuucccuccccccdTsdT sense
    1948-1967 6111 GGGGGGAGGGAAGGAGUGG 6112 GGGGGGAGGGAAGGAGUGGdTsdT antis
    1949-1968 6113 CACUCCUUCCCUCCCCCCC 6114 cAcuccuucccucccccccdTsdT sense
    1949-1968 6115 GGGGGGGAGGGAAGGAGUG 6116 GGGGGGGAGGGAAGGAGUGdTsdT antis
    1950-1969 6117 ACUCCUUCCCUCCCCCCCU 6118 AcuccuucccucccccccudTsdT sense
    1950-1969 6119 AGGGGGGGAGGGAAGGAGU 6120 AGGGGGGGAGGGAAGGAGUdTsdT antis
    1951-1970 6121 CUCCUUCCCUCCCCCCCUC 6122 cuccuucccucccccccucdTsdT sense
    1951-1970 6123 GAGGGGGGGAGGGAAGGAG 6124 GAGGGGGGGAGGGAAGGAGdTsdT antis
    1955-1974 6125 UUCCCUCCCCCCCUCUCCC 6126 uucccucccccccucucccdTsdT sense
    1955-1974 6127 GGGAGAGGGGGGGAGGGAA 6128 GGGAGAGGGGGGGAGGGAAdTsdT antis
    1956-1975 6129 UCCCUCCCCCCCUCUCCCA 6130 ucccucccccccucucccAdTsdT sense
    1956-1975 6131 UGGGAGAGGGGGGGAGGGA 6132 UGGGAGAGGGGGGGAGGGAdTsdT antis
    1965-1984 6133 CCCUCUCCCAGGUCCCUUG 6134 cccucucccAGGucccuuGdTsdT sense
    1965-1984 6135 CAAGGGACCUGGGAGAGGG 6136 cAAGGGACCUGGGAGAGGGdTsdT antis
    1971-1990 6137 CCCAGGUCCCUUGUAAAUA 6138 cccAGGucccuuGuAAAuAdTsdT sense
    1971-1990 6139 UAUUUACAAGGGACCUGGG 6140 uAUUuAcAAGGGACCUGGGdTsdT antis
    1988-2007 6141 UAGAACCAGCCCAGCCCAU 6142 uAGAAccAGcccAGcccAudTsdT sense
    1988-2007 6143 AUGGGCUGGGCUGGUUCUA 6144 AUGGGCUGGGCUGGUUCuAdTsdT antis
    2005-2024 6145 AUCUCUCGUCUUCCCUUCC 6146 AucucucGucuucccuuccdTsdT sense
    2005-2024 6147 GGAAGGGAAGACGAGAGAU 6148 GGAAGGGAAGACGAGAGAUdTsdT antis
    2006-2025 6149 UCUCUCGUCUUCCCUUCCC 6150 ucucucGucuucccuucccdTsdT sense
    2006-2025 6151 GGGAAGGGAAGACGAGAGA 6152 GGGAAGGGAAGACGAGAGAdTsdT antis
    2020-2039 6153 UUCCCUGGCCCCCUGGGUG 6154 uucccuGGcccccuGGGuGdTsdT sense
    2020-2039 6155 CACCCAGGGGGCCAGGGAA 6156 cACCcAGGGGGCcAGGGAAdTsdT antis
    2039-2058 6157 UAAAUAGAUUGUUAUAAUU 6158 uAAAuAGAuuGuuAuAAuudTsdT sense
    2039-2058 6159 AAUUAUAACAAUCUAUUUA 6160 AAUuAuAAcAAUCuAUUuAdTsdT antis
    2050-2069 6161 UUAUAAUUUUUUCUUAAAG 6162 uuAuAAuuuuuucuuAAAGdTsdT sense
    2050-2069 6163 CUUUAAGAAAAAAUUAUAA 6164 CUUuAAGAAAAAAUuAuAAdTsdT antis
    2052-2071 6165 AUAAUUUUUUCUUAAAGAA 6166 AuAAuuuuuucuuAAAGAAdTsdT sense
    2052-2071 6167 UUCUUUAAGAAAAAAUUAU 6168 UUCUUuAAGAAAAAAUuAUdTsdT antis
    2053-2072 6169 UAAUUUUUUCUUAAAGAAA 6170 uAAuuuuuucuuAAAGAAAdTsdT sense
    2053-2072 6171 UUUCUUUAAGAAAAAAUUA 6172 UUUCUUuAAGAAAAAAUuAdTsdT antis
    2054-2073 6173 AAUUUUUUCUUAAAGAAAA 6174 AAuuuuuucuuAAAGAAAAdTsdT sense
    2054-2073 6175 UUUUCUUUAAGAAAAAAUU 6176 UUUUCUUuAAGAAAAAAUUdTsdT antis
    2110-2129 6177 UACCCCUUCUUGUCCUCUG 6178 uAccccuucuuGuccucuGdTsdT sense
    2110-2129 6179 CAGAGGACAAGAAGGGGUA 6180 cAGAGGAcAAGAAGGGGuAdTsdT antis
    2112-2131 6181 CCCCUUCUUGUCCUCUGCU 6182 ccccuucuuGuccucuGcudTsdT sense
    2112-2131 6183 AGCAGAGGACAAGAAGGGG 6184 AGcAGAGGAcAAGAAGGGGdTsdT antis
    2113-2132 6185 CCCUUCUUGUCCUCUGCUC 6186 cccuucuuGuccucuGcucdTsdT sense
    2113-2132 6187 GAGCAGAGGACAAGAAGGG 6188 GAGcAGAGGAcAAGAAGGGdTsdT antis
    2114-2133 6189 CCUUCUUGUCCUCUGCUCC 6190 ccuucuuGuccucuGcuccdTsdT sense
    2114-2133 6191 GGAGCAGAGGACAAGAAGG 6192 GGAGcAGAGGAcAAGAAGGdTsdT antis
    2115-2134 6193 CUUCUUGUCCUCUGCUCCC 6194 cuucuuGuccucuGcucccdTsdT sense
    2115-2134 6195 GGGAGCAGAGGACAAGAAG 6196 GGGAGcAGAGGAcAAGAAGdTsdT antis
    2126-2145 6197 CUGCUCCCAAGGCUUCCUC 6198 cuGcucccAAGGcuuccucdTsdT sense
    2126-2145 6199 GAGGAAGCCUUGGGAGCAG 6200 GAGGAAGCCUUGGGAGcAGdTsdT antis
    2131-2150 6201 CCCAAGGCUUCCUCCCUCU 6202 cccAAGGcuuccucccucudTsdT sense
    2131-2150 6203 AGAGGGAGGAAGCCUUGGG 6204 AGAGGGAGGAAGCCUUGGGdTsdT antis
    2137-2156 6205 GCUUCCUCCCUCUCCCCAU 6206 GcuuccucccucuccccAudTsdT sense
    2137-2156 6207 AUGGGGAGAGGGAGGAAGC 6208 AUGGGGAGAGGGAGGAAGCdTsdT antis
    2138-2157 6209 CUUCCUCCCUCUCCCCAUC 6210 cuuccucccucuccccAucdTsdT sense
    2138-2157 6211 GAUGGGGAGAGGGAGGAAG 6212 GAUGGGGAGAGGGAGGAAGdTsdT antis
    2140-2159 6213 UCCUCCCUCUCCCCAUCCU 6214 uccucccucuccccAuccudTsdT sense
    2140-2159 6215 AGGAUGGGGAGAGGGAGGA 6216 AGGAUGGGGAGAGGGAGGAdTsdT antis
    2141-2160 6217 CCUCCCUCUCCCCAUCCUG 6218 ccucccucuccccAuccuGdTsdT sense
    2141-2160 6219 CAGGAUGGGGAGAGGGAGG 6220 cAGGAUGGGGAGAGGGAGGdTsdT antis
    2145-2164 6221 CCUCUCCCCAUCCUGGAAG 6222 ccucuccccAuccuGGAAGdTsdT sense
    2145-2164 6223 CUUCCAGGAUGGGGAGAGG 6224 CUUCcAGGAUGGGGAGAGGdTsdT antis
    2153-2172 6225 CAUCCUGGAAGGAGGGGAG 6226 cAuccuGGAAGGAGGGGAGdTsdT sense
    2153-2172 6227 CUCCCCUCCUUCCAGGAUG 6228 CUCCCCUCCUUCcAGGAUGdTsdT antis
    2172-2191 6229 UAGAGAGAGUCCCUGGUGU 6230 uAGAGAGAGucccuGGuGudTsdT sense
    2172-2191 6231 ACACCAGGGACUCUCUCUA 6232 AcACcAGGGACUCUCUCuAdTsdT antis
    2186-2205 6233 GGUGUCUUAGUUUCCACAG 6234 GGuGucuuAGuuuccAcAGdTsdT sense
    2186-2205 6235 CUGUGGAAACUAAGACACC 6236 CUGUGGAAACuAAGAcACCdTsdT antis
    2193-2212 6237 UAGUUUCCACAGUAAGGUU 6238 uAGuuuccAcAGuAAGGuudTsdT sense
    2193-2212 6239 AACCUUACUGUGGAAACUA 6240 AACCUuACUGUGGAAACuAdTsdT antis
    2240-2259 6241 AUUAUUGGCAUGAAACCCU 6242 AuuAuuGGcAuGAAAcccudTsdT sense
    2240-2259 6243 AGGGUUUCAUGCCAAUAAU 6244 AGGGUUUcAUGCcAAuAAUdTsdT antis
    62-81 6245 CUGGGCCGGAGCCGGAGCC 6246 cuGGGccGGAGccGGAGccdTsdT sense
    62-81 6247 GGCUCCGGCUCCGGCCCAG 6248 GGCUCCGGCUCCGGCCcAGdTsdT antis
    120-139 6249 GCGGCGGCAGAGGCAGCGG 6250 GcGGcGGcAGAGGcAGcGGdTsdT sense
    120-139 6251 CCGCUGCCUCUGCCGCCGC 6252 CCGCUGCCUCUGCCGCCGCdTsdT antis
    121-140 6253 CGGCGGCAGAGGCAGCGGC 6254 cGGcGGcAGAGGcAGcGGcdTsdT sense
    121-140 6255 GCCGCUGCCUCUGCCGCCG 6256 GCCGCUGCCUCUGCCGCCGdTsdT antis
    127-146 6257 CAGAGGCAGCGGCGGGGGC 6258 cAGAGGcAGcGGcGGGGGcdTsdT sense
    127-146 6259 GCCCCCGCCGCUGCCUCUG 6260 GCCCCCGCCGCUGCCUCUGdTsdT antis
    142-161 6261 GGGCAGCCCAGGCAGCCCG 6262 GGGcAGcccAGGcAGcccGdTsdT sense
    142-161 6263 CGGGCUGCCUGGGCUGCCC 6264 CGGGCUGCCUGGGCUGCCCdTsdT antis
    267-286 6265 GGAGGCGGAGGCGGAGGUG 6266 GGAGGcGGAGGcGGAGGuGdTsdT sense
    267-286 6267 CACCUCCGCCUCCGCCUCC 6268 cACCUCCGCCUCCGCCUCCdTsdT antis
    268-287 6269 GAGGCGGAGGCGGAGGUGG 6270 GAGGcGGAGGcGGAGGuGGdTsdT sense
    268-287 6271 CCACCUCCGCCUCCGCCUC 6272 CcACCUCCGCCUCCGCCUCdTsdT antis
    271-290 6273 GCGGAGGCGGAGGUGGUGG 6274 GcGGAGGcGGAGGuGGuGGdTsdT sense
    271-290 6275 CCACCACCUCCGCCUCCGC 6276 CcACcACCUCCGCCUCCGCdTsdT antis
    284-303 6277 UGGUGGCGGCGGCCCCGGG 6278 uGGuGGcGGcGGccccGGGdTsdT sense
    284-303 6279 CCCGGGGCCGCCGCCACCA 6280 CCCGGGGCCGCCGCcACcAdTsdT antis
    591-610 6281 UACCAGGCACGGCUGGCAG 6282 uAccAGGcAcGGcuGGcAGdTsdT sense
    591-610 6283 CUGCCAGCCGUGCCUGGUA 6284 CUGCcAGCCGUGCCUGGuAdTsdT antis
    1131-1150 6285 CUUCUCGGCCAGCCCAUCU 6286 cuucucGGccAGcccAucudTsdT sense
    1131-1150 6287 AGAUGGGCUGGCCGAGAAG 6288 AGAUGGGCUGGCCGAGAAGdTsdT antis
    1299-1318 6289 UCUUCAAAGACACCACCUG 6290 ucuucAAAGAcAccAccuGdTsdT sense
    1299-1318 6291 CAGGUGGUGUCUUUGAAGA 6292 cAGGUGGUGUCUUUGAAGAdTsdT antis
    1558-1577 6293 UCACCACUUCCUACAACCC 6294 ucAccAcuuccuAcAAcccdTsdT sense
    1558-1577 6295 GGGUUGUAGGAAGUGGUGA 6296 GGGUUGuAGGAAGUGGUGAdTsdT antis
    1927-1946 6297 CCCCUCCCCUCCCCCAGGC 6298 ccccuccccucccccAGGcdTsdT sense
    1927-1946 6299 GCCUGGGGGAGGGGAGGGG 6300 GCCUGGGGGAGGGGAGGGGdTsdT antis
    1928-1947 6301 CCCUCCCCUCCCCCAGGCU 6302 cccuccccucccccAGGcudTsdT sense
    1928-1947 6303 AGCCUGGGGGAGGGGAGGG 6304 AGCCUGGGGGAGGGGAGGGdTsdT antis
    2111-2130 6305 ACCCCUUCUUGUCCUCUGC 6306 AccccuucuuGuccucuGcdTsdT sense
    2111-2130 6307 GCAGAGGACAAGAAGGGGU 6308 GcAGAGGAcAAGAAGGGGUdTsdT antis
    2142-2161 6309 CUCCCUCUCCCCAUCCUGG 6310 cucccucuccccAuccuGGdTsdT sense
    2142-2161 6311 CCAGGAUGGGGAGAGGGAG 6312 CcAGGAUGGGGAGAGGGAGdTsdT antis
    2144-2163 6313 CCCUCUCCCCAUCCUGGAA 6314 cccucuccccAuccuGGAAdTsdT sense
    2144-2163 6315 UUCCAGGAUGGGGAGAGGG 6316 UUCcAGGAUGGGGAGAGGGdTsdT antis
    1671-1690 6317 CACCGACUACCCCUCCACG 6318 cAccGAcuAccccuccAcGdTsdT sense
    1671-1690 6319 CGUGGAGGGGUAGUCGGUG 6320 CGUGGAGGGGuAGUCGGUGdTsdT antis
    1673-1692 6321 CCGACUACCCCUCCACGUC 6322 ccGAcuAccccuccAcGucdTsdT sense
    1673-1692 6323 GACGUGGAGGGGUAGUCGG 6324 GACGUGGAGGGGuAGUCGGdTsdT antis
    1036-1055 6325 CUCGGUACUACCGUGCUCC 6326 cucGGuAcuAccGuGcuccdTsdT sense
    1036-1055 6327 GGAGCACGGUAGUACCGAG 6328 GGAGcACGGuAGuACCGAGdTsdT antis
    1035-1054 6329 UCUCGGUACUACCGUGCUC 6330 ucucGGuAcuAccGuGcucdTsdT sense
    1035-1054 6331 GAGCACGGUAGUACCGAGA 6332 GAGcACGGuAGuACCGAGAdTsdT antis
    1042-1061 6333 ACUACCGUGCUCCAGAACU 6334 AcuAccGuGcuccAGAAcudTsdT sense
    1042-1061 6335 AGUUCUGGAGCACGGUAGU 6336 AGUUCUGGAGcACGGuAGUdTsdT antis
    1674-1693 6337 CGACUACCCCUCCACGUCC 6338 cGAcuAccccuccAcGuccdTsdT sense
    1674-1693 6339 GGACGUGGAGGGGUAGUCG 6340 GGACGUGGAGGGGuAGUCGdTsdT antis
    1787-1806 6341 AACUACCCCCAGCAUCUAG 6342 AAcuAcccccAGcAucuAGdTsdT sense
    1787-1806 6343 CUAGAUGCUGGGGGUAGUU 6344 CuAGAUGCUGGGGGuAGUUdTsdT antis
    1034-1053 6345 CUCUCGGUACUACCGUGCU 6346 cucucGGuAcuAccGuGcudTsdT sense
    1034-1053 6347 AGCACGGUAGUACCGAGAG 6348 AGcACGGuAGuACCGAGAGdTsdT antis
    1202-1221 6349 AACGCCAACCAGGGAACAA 6350 AAcGccAAccAGGGAAcAAdTsdT sense
    1202-1221 6351 UUGUUCCCUGGUUGGCGUU 6352 UUGUUCCCUGGUUGGCGUUdTsdT antis
    776-795 6353 GGAGUAUGUGCCCGAGACG 6354 GGAGuAuGuGcccGAGAcGdTsdT sense
    776-795 6355 CGUCUCGGGCACAUACUCC 6356 CGUCUCGGGcAcAuACUCCdTsdT antis
    779-798 6357 GUAUGUGCCCGAGACGGUG 6358 GuAuGuGcccGAGAcGGuGdTsdT sense
    779-798 6359 CACCGUCUCGGGCACAUAC 6360 cACCGUCUCGGGcAcAuACdTsdT antis
    780-799 6361 UAUGUGCCCGAGACGGUGU 6362 uAuGuGcccGAGAcGGuGudTsdT sense
    780-799 6363 ACACCGUCUCGGGCACAUA 6364 AcACCGUCUCGGGcAcAuAdTsdT antis
    973-992 6365 UCUGCGAUUUUGGCAGUGC 6366 ucuGcGAuuuuGGcAGuGcdTsdT sense
    973-992 6367 GCACUGCCAAAAUCGCAGA 6368 GcACUGCcAAAAUCGcAGAdTsdT antis
    1038-1057 6369 CGGUACUACCGUGCUCCAG 6370 cGGuAcuAccGuGcuccAGdTsdT sense
    1038-1057 6371 CUGGAGCACGGUAGUACCG 6372 CUGGAGcACGGuAGuACCGdTsdT antis
    1041-1060 6373 UACUACCGUGCUCCAGAAC 6374 uAcuAccGuGcuccAGAAcdTsdT sense
    1041-1060 6375 GUUCUGGAGCACGGUAGUA 6376 GUUCUGGAGcACGGuAGuAdTsdT antis
    1043-1062 6377 CUACCGUGCUCCAGAACUC 6378 cuAccGuGcuccAGAAcucdTsdT sense
    1043-1062 6379 GAGUUCUGGAGCACGGUAG 6380 GAGUUCUGGAGcACGGuAGdTsdT antis
    1189-1208 6381 UCAAGGUACUAGGAACGCC 6382 ucAAGGuAcuAGGAAcGccdTsdT sense
    1189-1208 6383 GGCGUUCCUAGUACCUUGA 6384 GGCGUUCCuAGuACCUUGAdTsdT antis
    1190-1209 6385 CAAGGUACUAGGAACGCCA 6386 cAAGGuAcuAGGAAcGccAdTsdT sense
    1190-1209 6387 UGGCGUUCCUAGUACCUUG 6388 UGGCGUUCCuAGuACCUUGdTsdT antis
    1191-1210 6389 AAGGUACUAGGAACGCCAA 6390 AAGGuAcuAGGAAcGccAAdTsdT sense
    1191-1210 6391 UUGGCGUUCCUAGUACCUU 6392 UUGGCGUUCCuAGuACCUUdTsdT antis
    1192-1211 6393 AGGUACUAGGAACGCCAAC 6394 AGGuAcuAGGAAcGccAAcdTsdT sense
    1192-1211 6395 GUUGGCGUUCCUAGUACCU 6396 GUUGGCGUUCCuAGuACCUdTsdT antis
    1197-1216 6397 CUAGGAACGCCAACCAGGG 6398 cuAGGAAcGccAAccAGGGdTsdT sense
    1197-1216 6399 CCCUGGUUGGCGUUCCUAG 6400 CCCUGGUUGGCGUUCCuAGdTsdT antis
    1203-1222 6401 ACGCCAACCAGGGAACAAA 6402 AcGccAAccAGGGAAcAAAdTsdT sense
    1203-1222 6403 UUUGUUCCCUGGUUGGCGU 6404 UUUGUUCCCUGGUUGGCGUdTsdT antis
    1670-1689 6405 CCACCGACUACCCCUCCAC 6406 ccAccGAcuAccccuccAcdTsdT sense
    1670-1689 6407 GUGGAGGGGUAGUCGGUGG 6408 GUGGAGGGGuAGUCGGUGGdTsdT antis
    1672-1691 6409 ACCGACUACCCCUCCACGU 6410 AccGAcuAccccuccAcGudTsdT sense
    1672-1691 6411 ACGUGGAGGGGUAGUCGGU 6412 ACGUGGAGGGGuAGUCGGUdTsdT antis
    1780-1799 6413 GUAAAUGAACUACCCCCAG 6414 GuAAAuGAAcuAcccccAGdTsdT sense
    1780-1799 6415 CUGGGGGUAGUUCAUUUAC 6416 CUGGGGGuAGUUcAUUuACdTsdT antis
    1786-1805 6417 GAACUACCCCCAGCAUCUA 6418 GAAcuAcccccAGcAucuAdTsdT sense
    1786-1805 6419 UAGAUGCUGGGGGUAGUUC 6420 uAGAUGCUGGGGGuAGUUCdTsdT antis
    352-371 6421 GGGCUAUGGGUGGGGGCGU 6422 GGGcuAuGGGuGGGGGcGudTsdT sense
    352-371 6423 ACGCCCCCACCCAUAGCCC 6424 ACGCCCCcACCcAuAGCCCdTsdT antis
    354-373 6425 GCUAUGGGUGGGGGCGUGG 6426 GcuAuGGGuGGGGGcGuGGdTsdT sense
    354-373 6427 CCACGCCCCCACCCAUAGC 6428 CcACGCCCCcACCcAuAGCdTsdT antis
    521-540 6429 CCCAGAGCGUUCCCAAGAA 6430 cccAGAGcGuucccAAGAAdTsdT sense
    521-540 6431 UUCUUGGGAACGCUCUGGG 6432 UUCUUGGGAACGCUCUGGGdTsdT antis
    523-542 6433 CAGAGCGUUCCCAAGAAGU 6434 cAGAGcGuucccAAGAAGudTsdT sense
    523-542 6435 ACUUCUUGGGAACGCUCUG 6436 ACUUCUUGGGAACGCUCUGdTsdT antis
    524-543 6437 AGAGCGUUCCCAAGAAGUG 6438 AGAGcGuucccAAGAAGuGdTsdT sense
    524-543 6439 CACUUCUUGGGAACGCUCU 6440 cACUUCUUGGGAACGCUCUdTsdT antis
    527-546 6441 GCGUUCCCAAGAAGUGGCU 6442 GcGuucccAAGAAGuGGcudTsdT sense
    527-546 6443 AGCCACUUCUUGGGAACGC 6444 AGCcACUUCUUGGGAACGCdTsdT antis
    550-569 6445 CUGACAUCAAAGUGAUUGG 6446 cuGAcAucAAAGuGAuuGGdTsdT sense
    550-569 6447 CCAAUCACUUUGAUGUCAG 6448 CcAAUcACUUUGAUGUcAGdTsdT antis
    568-587 6449 GUAAUGGCUCAUUCGGAGU 6450 GuAAuGGcucAuucGGAGudTsdT sense
    568-587 6451 ACUCCGAAUGAGCCAUUAC 6452 ACUCCGAAUGAGCcAUuACdTsdT antis
    569-588 6453 UAAUGGCUCAUUCGGAGUA 6454 uAAuGGcucAuucGGAGuAdTsdT sense
    569-588 6455 UACUCCGAAUGAGCCAUUA 6456 uACUCCGAAUGAGCcAUuAdTsdT antis
    570-589 6457 AAUGGCUCAUUCGGAGUAG 6458 AAuGGcucAuucGGAGuAGdTsdT sense
    570-589 6459 CUACUCCGAAUGAGCCAUU 6460 CuACUCCGAAUGAGCcAUUdTsdT antis
    572-591 6461 UGGCUCAUUCGGAGUAGUA 6462 uGGcucAuucGGAGuAGuAdTsdT sense
    572-591 6463 UACUACUCCGAAUGAGCCA 6464 uACuACUCCGAAUGAGCcAdTsdT antis
    626-645 6465 GGCCAUCAAGAAGGUUCUU 6466 GGccAucAAGAAGGuucuudTsdT sense
    626-645 6467 AAGAACCUUCUUGAUGGCC 6468 AAGAACCUUCUUGAUGGCCdTsdT antis
    688-707 6469 AGCUGGACCACUGCAAUAU 6470 AGcuGGAccAcuGcAAuAudTsdT sense
    688-707 6471 AUAUUGCAGUGGUCCAGCU 6472 AuAUUGcAGUGGUCcAGCUdTsdT antis
    693-712 6473 GACCACUGCAAUAUUGUGA 6474 GAccAcuGcAAuAuuGuGAdTsdT sense
    693-712 6475 UCACAAUAUUGCAGUGGUC 6476 UcAcAAuAUUGcAGUGGUCdTsdT antis
    697-716 6477 ACUGCAAUAUUGUGAGGCU 6478 AcuGcAAuAuuGuGAGGcudTsdT sense
    697-716 6479 AGCCUCACAAUAUUGCAGU 6480 AGCCUcAcAAuAUUGcAGUdTsdT antis
    724-743 6481 UUUUCUACUCCAGUGGGGA 6482 uuuucuAcuccAGuGGGGAdTsdT sense
    724-743 6483 UCCCCACUGGAGUAGAAAA 6484 UCCCcACUGGAGuAGAAAAdTsdT antis
    725-744 6485 UUUCUACUCCAGUGGGGAG 6486 uuucuAcuccAGuGGGGAGdTsdT sense
    725-744 6487 CUCCCCACUGGAGUAGAAA 6488 CUCCCcACUGGAGuAGAAAdTsdT antis
    726-745 6489 UUCUACUCCAGUGGGGAGA 6490 uucuAcuccAGuGGGGAGAdTsdT sense
    726-745 6491 UCUCCCCACUGGAGUAGAA 6492 UCUCCCcACUGGAGuAGAAdTsdT antis
    727-746 6493 UCUACUCCAGUGGGGAGAA 6494 ucuAcuccAGuGGGGAGAAdTsdT sense
    727-746 6495 UUCUCCCCACUGGAGUAGA 6496 UUCUCCCcACUGGAGuAGAdTsdT antis
    757-776 6497 UGUAUUUGAAUCUGGUGCU 6498 uGuAuuuGAAucuGGuGcudTsdT sense
    757-776 6499 AGCACCAGAUUCAAAUACA 6500 AGcACcAGAUUcAAAuAcAdTsdT antis
    759-778 6501 UAUUUGAAUCUGGUGCUGG 6502 uAuuuGAAucuGGuGcuGGdTsdT sense
    759-778 6503 CCAGCACCAGAUUCAAAUA 6504 CcAGcACcAGAUUcAAAuAdTsdT antis
    760-779 6505 AUUUGAAUCUGGUGCUGGA 6506 AuuuGAAucuGGuGcuGGAdTsdT sense
    760-779 6507 UCCAGCACCAGAUUCAAAU 6508 UCcAGcACcAGAUUcAAAUdTsdT antis
    762-781 6509 UUGAAUCUGGUGCUGGAGU 6510 uuGAAucuGGuGcuGGAGudTsdT sense
    762-781 6511 ACUCCAGCACCAGAUUCAA 6512 ACUCcAGcACcAGAUUcAAdTsdT antis
    763-782 6513 UGAAUCUGGUGCUGGAGUA 6514 uGAAucuGGuGcuGGAGuAdTsdT sense
    763-782 6515 UACUCCAGCACCAGAUUCA 6516 uACUCcAGcACcAGAUUcAdTsdT antis
    775-794 6517 UGGAGUAUGUGCCCGAGAC 6518 uGGAGuAuGuGcccGAGAcdTsdT sense
    775-794 6519 GUCUCGGGCACAUACUCCA 6520 GUCUCGGGcAcAuACUCcAdTsdT antis
    778-797 6521 AGUAUGUGCCCGAGACGGU 6522 AGuAuGuGcccGAGAcGGudTsdT sense
    778-797 6523 ACCGUCUCGGGCACAUACU 6524 ACCGUCUCGGGcAcAuACUdTsdT antis
    854-873 6525 CAAGGUGUACAUGUACCAG 6526 cAAGGuGuAcAuGuAccAGdTsdT sense
    854-873 6527 CUGGUACAUGUACACCUUG 6528 CUGGuAcAUGuAcACCUUGdTsdT antis
    855-874 6529 AAGGUGUACAUGUACCAGC 6530 AAGGuGuAcAuGuAccAGcdTsdT sense
    855-874 6531 GCUGGUACAUGUACACCUU 6532 GCUGGuAcAUGuAcACCUUdTsdT antis
    856-875 6533 AGGUGUACAUGUACCAGCU 6534 AGGuGuAcAuGuAccAGcudTsdT sense
    856-875 6535 AGCUGGUACAUGUACACCU 6536 AGCUGGuAcAUGuAcACCUdTsdT antis
    857-876 6537 GGUGUACAUGUACCAGCUC 6538 GGuGuAcAuGuAccAGcucdTsdT sense
    857-876 6539 GAGCUGGUACAUGUACACC 6540 GAGCUGGuAcAUGuAcACCdTsdT antis
    915-934 6541 CACCGUGACAUCAAGCCCC 6542 cAccGuGAcAucAAGccccdTsdT sense
    915-934 6543 GGGGCUUGAUGUCACGGUG 6544 GGGGCUUGAUGUcACGGUGdTsdT antis
    938-957 6545 UUUGCUUGUGGACCCUGAC 6546 uuuGcuuGuGGAcccuGAcdTsdT sense
    938-957 6547 GUCAGGGUCCACAAGCAAA 6548 GUcAGGGUCcAcAAGcAAAdTsdT antis
    945-964 6549 GUGGACCCUGACACUGCUG 6550 GuGGAcccuGAcAcuGcuGdTsdT sense
    945-964 6551 CAGCAGUGUCAGGGUCCAC 6552 cAGcAGUGUcAGGGUCcACdTsdT antis
    971-990 6553 GCUCUGCGAUUUUGGCAGU 6554 GcucuGcGAuuuuGGcAGudTsdT sense
    971-990 6555 ACUGCCAAAAUCGCAGAGC 6556 ACUGCcAAAAUCGcAGAGCdTsdT antis
    972-991 6557 CUCUGCGAUUUUGGCAGUG 6558 cucuGcGAuuuuGGcAGuGdTsdT sense
    972-991 6559 CACUGCCAAAAUCGCAGAG 6560 cACUGCcAAAAUCGcAGAGdTsdT antis
    975-994 6561 UGCGAUUUUGGCAGUGCAA 6562 uGcGAuuuuGGcAGuGcAAdTsdT sense
    975-994 6563 UUGCACUGCCAAAAUCGCA 6564 UUGcACUGCcAAAAUCGcAdTsdT antis
    979-998 6565 AUUUUGGCAGUGCAAAGCA 6566 AuuuuGGcAGuGcAAAGcAdTsdT sense
    979-998 6567 UGCUUUGCACUGCCAAAAU 6568 UGCUUUGcACUGCcAAAAUdTsdT antis
    1037-1056 6569 UCGGUACUACCGUGCUCCA 6570 ucGGuAcuAccGuGcuccAdTsdT sense
    1037-1056 6571 UGGAGCACGGUAGUACCGA 6572 UGGAGcACGGuAGuACCGAdTsdT antis
    1040-1059 6573 GUACUACCGUGCUCCAGAA 6574 GuAcuAccGuGcuccAGAAdTsdT sense
    1040-1059 6575 UUCUGGAGCACGGUAGUAC 6576 UUCUGGAGcACGGuAGuACdTsdT antis
    1169-1188 6577 GGACCAGCUUGUGGAGAUC 6578 GGAccAGcuuGuGGAGAucdTsdT sense
    1169-1188 6579 GAUCUCCACAAGCUGGUCC 6580 GAUCUCcAcAAGCUGGUCCdTsdT antis
    1174-1193 6581 AGCUUGUGGAGAUCAUCAA 6582 AGcuuGuGGAGAucAucAAdTsdT sense
    1174-1193 6583 UUGAUGAUCUCCACAAGCU 6584 UUGAUGAUCUCcAcAAGCUdTsdT antis
    1178-1197 6585 UGUGGAGAUCAUCAAGGUA 6586 uGuGGAGAucAucAAGGuAdTsdT sense
    1178-1197 6587 UACCUUGAUGAUCUCCACA 6588 uACCUUGAUGAUCUCcAcAdTsdT antis
    1183-1202 6589 AGAUCAUCAAGGUACUAGG 6590 AGAucAucAAGGuAcuAGGdTsdT sense
    1183-1202 6591 CCUAGUACCUUGAUGAUCU 6592 CCuAGuACCUUGAUGAUCUdTsdT antis
    1193-1212 6593 GGUACUAGGAACGCCAACC 6594 GGuAcuAGGAAcGccAAccdTsdT sense
    1193-1212 6595 GGUUGGCGUUCCUAGUACC 6596 GGUUGGCGUUCCuAGuACCdTsdT antis
    1194-1213 6597 GUACUAGGAACGCCAACCA 6598 GuAcuAGGAAcGccAAccAdTsdT sense
    1194-1213 6599 UGGUUGGCGUUCCUAGUAC 6600 UGGUUGGCGUUCCuAGuACdTsdT antis
    1195-1214 6601 UACUAGGAACGCCAACCAG 6602 uAcuAGGAAcGccAAccAGdTsdT sense
    1195-1214 6603 CUGGUUGGCGUUCCUAGUA 6604 CUGGUUGGCGUUCCuAGuAdTsdT antis
    1198-1217 6605 UAGGAACGCCAACCAGGGA 6606 uAGGAAcGccAAccAGGGAdTsdT sense
    1198-1217 6607 UCCCUGGUUGGCGUUCCUA 6608 UCCCUGGUUGGCGUUCCuAdTsdT antis
    1199-1218 6609 AGGAACGCCAACCAGGGAA 6610 AGGAAcGccAAccAGGGAAdTsdT sense
    1199-1218 6611 UUCCCUGGUUGGCGUUCCU 6612 UUCCCUGGUUGGCGUUCCUdTsdT antis
    1200-1219 6613 GGAACGCCAACCAGGGAAC 6614 GGAAcGccAAccAGGGAAcdTsdT sense
    1200-1219 6615 GUUCCCUGGUUGGCGUUCC 6616 GUUCCCUGGUUGGCGUUCCdTsdT antis
    1201-1220 6617 GAACGCCAACCAGGGAACA 6618 GAAcGccAAccAGGGAAcAdTsdT sense
    1201-1220 6619 UGUUCCCUGGUUGGCGUUC 6620 UGUUCCCUGGUUGGCGUUCdTsdT antis
    1206-1225 6621 CCAACCAGGGAACAAAUCC 6622 ccAAccAGGGAAcAAAuccdTsdT sense
    1206-1225 6623 GGAUUUGUUCCCUGGUUGG 6624 GGAUUUGUUCCCUGGUUGGdTsdT antis
    1208-1227 6625 AACCAGGGAACAAAUCCGA 6626 AAccAGGGAAcAAAuccGAdTsdT sense
    1208-1227 6627 UCGGAUUUGUUCCCUGGUU 6628 UCGGAUUUGUUCCCUGGUUdTsdT antis
    1218-1237 6629 CAAAUCCGAGAGAUGAACC 6630 cAAAuccGAGAGAuGAAccdTsdT sense
    1218-1237 6631 GGUUCAUCUCUCGGAUUUG 6632 GGUUcAUCUCUCGGAUUUGdTsdT antis
    1220-1239 6633 AAUCCGAGAGAUGAACCCU 6634 AAuccGAGAGAuGAAcccudTsdT sense
    1220-1239 6635 AGGGUUCAUCUCUCGGAUU 6636 AGGGUUcAUCUCUCGGAUUdTsdT antis
    1221-1240 6637 AUCCGAGAGAUGAACCCUA 6638 AuccGAGAGAuGAAcccuAdTsdT sense
    1221-1240 6639 UAGGGUUCAUCUCUCGGAU 6640 uAGGGUUcAUCUCUCGGAUdTsdT antis
    1453-1472 6641 CCCCCCUGUUCAACUUCAG 6642 ccccccuGuucAAcuucAGdTsdT sense
    1453-1472 6643 CUGAAGUUGAACAGGGGGG 6644 CUGAAGUUGAAcAGGGGGGdTsdT antis
    1675-1694 6645 GACUACCCCUCCACGUCCA 6646 GAcuAccccuccAcGuccAdTsdT sense
    1675-1694 6647 UGGACGUGGAGGGGUAGUC 6648 UGGACGUGGAGGGGuAGUCdTsdT antis
    1676-1695 6649 ACUACCCCUCCACGUCCAU 6650 AcuAccccuccAcGuccAudTsdT sense
    1676-1695 6651 AUGGACGUGGAGGGGUAGU 6652 AUGGACGUGGAGGGGuAGUdTsdT antis
    1677-1696 6653 CUACCCCUCCACGUCCAUC 6654 cuAccccuccAcGuccAucdTsdT sense
    1677-1696 6655 GAUGGACGUGGAGGGGUAG 6656 GAUGGACGUGGAGGGGuAGdTsdT antis
    1703-1722 6657 GCCCAAGUGGCGCUGGGAA 6658 GcccAAGuGGcGcuGGGAAdTsdT sense
    1703-1722 6659 UUCCCAGCGCCACUUGGGC 6660 UUCCcAGCGCcACUUGGGCdTsdT antis
    1706-1725 6661 CAAGUGGCGCUGGGAAGGG 6662 cAAGuGGcGcuGGGAAGGGdTsdT sense
    1706-1725 6663 CCCUUCCCAGCGCCACUUG 6664 CCCUUCCcAGCGCcACUUGdTsdT antis
    1752-1771 6665 GGCUGGGCCCCUAGACUAG 6666 GGcuGGGccccuAGAcuAGdTsdT sense
    1752-1771 6667 CUAGUCUAGGGGCCCAGCC 6668 CuAGUCuAGGGGCCcAGCCdTsdT antis
    1755-1774 6669 UGGGCCCCUAGACUAGAGG 6670 uGGGccccuAGAcuAGAGGdTsdT sense
    1755-1774 6671 CCUCUAGUCUAGGGGCCCA 6672 CCUCuAGUCuAGGGGCCcAdTsdT antis
    1758-1777 6673 GCCCCUAGACUAGAGGGCA 6674 GccccuAGAcuAGAGGGcAdTsdT sense
    1758-1777 6675 UGCCCUCUAGUCUAGGGGC 6676 UGCCCUCuAGUCuAGGGGCdTsdT antis
    1761-1780 6677 CCUAGACUAGAGGGCAGAG 6678 ccuAGAcuAGAGGGcAGAGdTsdT sense
    1761-1780 6679 CUCUGCCCUCUAGUCUAGG 6680 CUCUGCCCUCuAGUCuAGGdTsdT antis
    1765-1784 6681 GACUAGAGGGCAGAGGUAA 6682 GAcuAGAGGGcAGAGGuAAdTsdT sense
    1765-1784 6683 UUACCUCUGCCCUCUAGUC 6684 UuACCUCUGCCCUCuAGUCdTsdT antis
    1777-1796 6685 GAGGUAAAUGAACUACCCC 6686 GAGGuAAAuGAAcuAccccdTsdT sense
    1777-1796 6687 GGGGUAGUUCAUUUACCUC 6688 GGGGuAGUUcAUUuACCUCdTsdT antis
    1778-1797 6689 AGGUAAAUGAACUACCCCC 6690 AGGuAAAuGAAcuAcccccdTsdT sense
    1778-1797 6691 GGGGGUAGUUCAUUUACCU 6692 GGGGGuAGUUcAUUuACCUdTsdT antis
    1779-1798 6693 GGUAAAUGAACUACCCCCA 6694 GGuAAAuGAAcuAcccccAdTsdT sense
    1779-1798 6695 UGGGGGUAGUUCAUUUACC 6696 UGGGGGuAGUUcAUUuACCdTsdT antis
    1781-1800 6697 UAAAUGAACUACCCCCAGC 6698 uAAAuGAAcuAcccccAGcdTsdT sense
    1781-1800 6699 GCUGGGGGUAGUUCAUUUA 6700 GCUGGGGGuAGUUcAUUuAdTsdT antis
    1792-1811 6701 CCCCCAGCAUCUAGGCCUC 6702 cccccAGcAucuAGGccucdTsdT sense
    1792-1811 6703 GAGGCCUAGAUGCUGGGGG 6704 GAGGCCuAGAUGCUGGGGGdTsdT antis
    1796-1815 6705 CAGCAUCUAGGCCUCCCUC 6706 cAGcAucuAGGccucccucdTsdT sense
    1796-1815 6707 GAGGGAGGCCUAGAUGCUG 6708 GAGGGAGGCCuAGAUGCUGdTsdT antis
    1885-1904 6709 AGGACGGGGUUUGGGGGUG 6710 AGGAcGGGGuuuGGGGGuGdTsdT sense
    1885-1904 6711 CACCCCCAAACCCCGUCCU 6712 cACCCCcAAACCCCGUCCUdTsdT antis
    522-541 6713 CCAGAGCGUUCCCAAGAAG 6714 ccAGAGcGuucccAAGAAGdTsdT sense
    522-541 6715 CUUCUUGGGAACGCUCUGG 6716 CUUCUUGGGAACGCUCUGGdTsdT antis
    526-545 6717 AGCGUUCCCAAGAAGUGGC 6718 AGcGuucccAAGAAGuGGcdTsdT sense
    526-545 6719 GCCACUUCUUGGGAACGCU 6720 GCcACUUCUUGGGAACGCUdTsdT antis
    700-719 6721 GCAAUAUUGUGAGGCUGCG 6722 GcAAuAuuGuGAGGcuGcGdTsdT sense
    700-719 6723 CGCAGCCUCACAAUAUUGC 6724 CGcAGCCUcAcAAuAUUGCdTsdT antis
    873-892 6725 CUCUUCCGGAGCUUGGCCU 6726 cucuuccGGAGcuuGGccudTsdT sense
    873-892 6727 AGGCCAAGCUCCGGAAGAG 6728 AGGCcAAGCUCCGGAAGAGdTsdT antis
    1256-1275 6729 GUUCCCCCAGAUCAAAGCU 6730 GuucccccAGAucAAAGcudTsdT sense
    1256-1275 6731 AGCUUUGAUCUGGGGGAAC 6732 AGCUUUGAUCUGGGGGAACdTsdT antis
    1317-1336 6733 GAGGCCAUUGCACUCUGCU 6734 GAGGccAuuGcAcucuGcudTsdT sense
    1317-1336 6735 AGCAGAGUGCAAUGGCCUC 6736 AGcAGAGUGcAAUGGCCUCdTsdT antis
    1512-1531 6737 CUCAUCCCUCCUCACUUGA 6738 cucAucccuccucAcuuGAdTsdT sense
    1512-1531 6739 UCAAGUGAGGAGGGAUGAG 6740 UcAAGUGAGGAGGGAUGAGdTsdT antis
    1764-1783 6741 AGACUAGAGGGCAGAGGUA 6742 AGAcuAGAGGGcAGAGGuAdTsdT sense
    1764-1783 6743 UACCUCUGCCCUCUAGUCU 6744 uACCUCUGCCCUCuAGUCUdTsdT antis
    236-255 6745 CCGGGCGCGGACCAGCUCG 6746 ccGGGcGcGGAccAGcucGdTsdT sense
    236-255 6747 CGAGCUGGUCCGCGCCCGG 6748 CGAGCUGGUCCGCGCCCGGdTsdT antis
    914-933 6749 UCACCGUGACAUCAAGCCC 6750 ucAccGuGAcAucAAGcccdTsdT sense
    914-933 6751 GGGCUUGAUGUCACGGUGA 6752 GGGCUUGAUGUcACGGUGAdTsdT antis
    234-253 6753 GGCCGGGCGCGGACCAGCU 6754 GGccGGGcGcGGAccAGcudTsdT sense
    234-253 6755 AGCUGGUCCGCGCCCGGCC 6756 AGCUGGUCCGCGCCCGGCCdTsdT antis
    520-539 6757 GCCCAGAGCGUUCCCAAGA 6758 GcccAGAGcGuucccAAGAdTsdT sense
    520-539 6759 UCUUGGGAACGCUCUGGGC 6760 UCUUGGGAACGCUCUGGGCdTsdT antis
    525-544 6761 GAGCGUUCCCAAGAAGUGG 6762 GAGcGuucccAAGAAGuGGdTsdT sense
    525-544 6763 CCACUUCUUGGGAACGCUC 6764 CcACUUCUUGGGAACGCUCdTsdT antis
    549-568 6765 ACUGACAUCAAAGUGAUUG 6766 AcuGAcAucAAAGuGAuuGdTsdT sense
    549-568 6767 CAAUCACUUUGAUGUCAGU 6768 cAAUcACUUUGAUGUcAGUdTsdT antis
    555-574 6769 AUCAAAGUGAUUGGUAAUG 6770 AucAAAGuGAuuGGuAAuGdTsdT sense
    555-574 6771 CAUUACCAAUCACUUUGAU 6772 cAUuACcAAUcACUUUGAUdTsdT antis
    558-577 6773 AAAGUGAUUGGUAAUGGCU 6774 AAAGuGAuuGGuAAuGGcudTsdT sense
    558-577 6775 AGCCAUUACCAAUCACUUU 6776 AGCcAUuACcAAUcACUUUdTsdT antis
    567-586 6777 GGUAAUGGCUCAUUCGGAG 6778 GGuAAuGGcucAuucGGAGdTsdT sense
    567-586 6779 CUCCGAAUGAGCCAUUACC 6780 CUCCGAAUGAGCcAUuACCdTsdT antis
    571-590 6781 AUGGCUCAUUCGGAGUAGU 6782 AuGGcucAuucGGAGuAGudTsdT sense
    571-590 6783 ACUACUCCGAAUGAGCCAU 6784 ACuACUCCGAAUGAGCcAUdTsdT antis
    685-704 6785 GUAAGCUGGACCACUGCAA 6786 GuAAGcuGGAccAcuGcAAdTsdT sense
    685-704 6787 UUGCAGUGGUCCAGCUUAC 6788 UUGcAGUGGUCcAGCUuACdTsdT antis
    764-783 6789 GAAUCUGGUGCUGGAGUAU 6790 GAAucuGGuGcuGGAGuAudTsdT sense
    764-783 6791 AUACUCCAGCACCAGAUUC 6792 AuACUCcAGcACcAGAUUCdTsdT antis
    777-796 6793 GAGUAUGUGCCCGAGACGG 6794 GAGuAuGuGcccGAGAcGGdTsdT sense
    777-796 6795 CCGUCUCGGGCACAUACUC 6796 CCGUCUCGGGcAcAuACUCdTsdT antis
    783-802 6797 GUGCCCGAGACGGUGUACC 6798 GuGcccGAGAcGGuGuAccdTsdT sense
    783-802 6799 GGUACACCGUCUCGGGCAC 6800 GGuAcACCGUCUCGGGcACdTsdT antis
    802-821 6801 GAGUGGCCCGCCACUUCAC 6802 GAGuGGcccGccAcuucAcdTsdT sense
    802-821 6803 GUGAAGUGGCGGGCCACUC 6804 GUGAAGUGGCGGGCcACUCdTsdT antis
    818-837 6805 CACCAAGGCCAAGCUGAUC 6806 cAccAAGGccAAGcuGAucdTsdT sense
    818-837 6807 GAUCAGCUUGGCCUUGGUG 6808 GAUcAGCUUGGCCUUGGUGdTsdT antis
    852-871 6809 AUCAAGGUGUACAUGUACC 6810 AucAAGGuGuAcAuGuAccdTsdT sense
    852-871 6811 GGUACAUGUACACCUUGAU 6812 GGuAcAUGuAcACCUUGAUdTsdT antis
    853-872 6813 UCAAGGUGUACAUGUACCA 6814 ucAAGGuGuAcAuGuAccAdTsdT sense
    853-872 6815 UGGUACAUGUACACCUUGA 6816 UGGuAcAUGuAcACCUUGAdTsdT antis
    937-956 6817 AUUUGCUUGUGGACCCUGA 6818 AuuuGcuuGuGGAcccuGAdTsdT sense
    937-956 6819 UCAGGGUCCACAAGCAAAU 6820 UcAGGGUCcAcAAGcAAAUdTsdT antis
    942-961 6821 CUUGUGGACCCUGACACUG 6822 cuuGuGGAcccuGAcAcuGdTsdT sense
    942-961 6823 CAGUGUCAGGGUCCACAAG 6824 cAGUGUcAGGGUCcAcAAGdTsdT antis
    967-986 6825 UCAAGCUCUGCGAUUUUGG 6826 ucAAGcucuGcGAuuuuGGdTsdT sense
    967-986 6827 CCAAAAUCGCAGAGCUUGA 6828 CcAAAAUCGcAGAGCUUGAdTsdT antis
    968-987 6829 CAAGCUCUGCGAUUUUGGC 6830 cAAGcucuGcGAuuuuGGcdTsdT sense
    968-987 6831 GCCAAAAUCGCAGAGCUUG 6832 GCcAAAAUCGcAGAGCUUGdTsdT antis
    976-995 6833 GCGAUUUUGGCAGUGCAAA 6834 GcGAuuuuGGcAGuGcAAAdTsdT sense
    976-995 6835 UUUGCACUGCCAAAAUCGC 6836 UUUGcACUGCcAAAAUCGCdTsdT antis
     984-1003 6837 GGCAGUGCAAAGCAGCUGG 6838 GGcAGuGcAAAGcAGcuGGdTsdT sense
     984-1003 6839 CCAGCUGCUUUGCACUGCC 6840 CcAGCUGCUUUGcACUGCCdTsdT antis
    1039-1058 6841 GGUACUACCGUGCUCCAGA 6842 GGuAcuAccGuGcuccAGAdTsdT sense
    1039-1058 6843 UCUGGAGCACGGUAGUACC 6844 UCUGGAGcACGGuAGuACCdTsdT antis
    1044-1063 6845 UACCGUGCUCCAGAACUCA 6846 uAccGuGcuccAGAAcucAdTsdT sense
    1044-1063 6847 UGAGUUCUGGAGCACGGUA 6848 UGAGUUCUGGAGcACGGuAdTsdT antis
    1185-1204 6849 AUCAUCAAGGUACUAGGAA 6850 AucAucAAGGuAcuAGGAAdTsdT sense
    1185-1204 6851 UUCCUAGUACCUUGAUGAU 6852 UUCCuAGuACCUUGAUGAUdTsdT antis
    1188-1207 6853 AUCAAGGUACUAGGAACGC 6854 AucAAGGuAcuAGGAAcGcdTsdT sense
    1188-1207 6855 GCGUUCCUAGUACCUUGAU 6856 GCGUUCCuAGuACCUUGAUdTsdT antis
    1196-1215 6857 ACUAGGAACGCCAACCAGG 6858 AcuAGGAAcGccAAccAGGdTsdT sense
    1196-1215 6859 CCUGGUUGGCGUUCCUAGU 6860 CCUGGUUGGCGUUCCuAGUdTsdT antis
    1204-1223 6861 CGCCAACCAGGGAACAAAU 6862 cGccAAccAGGGAAcAAAudTsdT sense
    1204-1223 6863 AUUUGUUCCCUGGUUGGCG 6864 AUUUGUUCCCUGGUUGGCGdTsdT antis
    1213-1232 6865 GGGAACAAAUCCGAGAGAU 6866 GGGAAcAAAuccGAGAGAudTsdT sense
    1213-1232 6867 AUCUCUCGGAUUUGUUCCC 6868 AUCUCUCGGAUUUGUUCCCdTsdT antis
    1215-1234 6869 GAACAAAUCCGAGAGAUGA 6870 GAAcAAAuccGAGAGAuGAdTsdT sense
    1215-1234 6871 UCAUCUCUCGGAUUUGUUC 6872 UcAUCUCUCGGAUUUGUUCdTsdT antis
    1216-1235 6873 AACAAAUCCGAGAGAUGAA 6874 AAcAAAuccGAGAGAuGAAdTsdT sense
    1216-1235 6875 UUCAUCUCUCGGAUUUGUU 6876 UUcAUCUCUCGGAUUUGUUdTsdT antis
    1217-1236 6877 ACAAAUCCGAGAGAUGAAC 6878 AcAAAuccGAGAGAuGAAcdTsdT sense
    1217-1236 6879 GUUCAUCUCUCGGAUUUGU 6880 GUUcAUCUCUCGGAUUUGUdTsdT antis
    1429-1448 6881 AGCUCCCCAACGACCGCCC 6882 AGcuccccAAcGAccGcccdTsdT sense
    1429-1448 6883 GGGCGGUCGUUGGGGAGCU 6884 GGGCGGUCGUUGGGGAGCUdTsdT antis
    1430-1449 6885 GCUCCCCAACGACCGCCCG 6886 GcuccccAAcGAccGcccGdTsdT sense
    1430-1449 6887 CGGGCGGUCGUUGGGGAGC 6888 CGGGCGGUCGUUGGGGAGCdTsdT antis
    1580-1599 6889 CUCACAAGCUUUAACUGAA 6890 cucAcAAGcuuuAAcuGAAdTsdT sense
    1580-1599 6891 UUCAGUUAAAGCUUGUGAG 6892 UUcAGUuAAAGCUUGUGAGdTsdT antis
    1667-1686 6893 GCCCCACCGACUACCCCUC 6894 GccccAccGAcuAccccucdTsdT sense
    1667-1686 6895 GAGGGGUAGUCGGUGGGGC 6896 GAGGGGuAGUCGGUGGGGCdTsdT antis
    1669-1688 6897 CCCACCGACUACCCCUCCA 6898 cccAccGAcuAccccuccAdTsdT sense
    1669-1688 6899 UGGAGGGGUAGUCGGUGGG 6900 UGGAGGGGuAGUCGGUGGGdTsdT antis
    1682-1701 6901 CCUCCACGUCCAUCUGGGA 6902 ccuccAcGuccAucuGGGAdTsdT sense
    1682-1701 6903 UCCCAGAUGGACGUGGAGG 6904 UCCcAGAUGGACGUGGAGGdTsdT antis
    1685-1704 6905 CCACGUCCAUCUGGGAAGG 6906 ccAcGuccAucuGGGAAGGdTsdT sense
    1685-1704 6907 CCUUCCCAGAUGGACGUGG 6908 CCUUCCcAGAUGGACGUGGdTsdT antis
    1704-1723 6909 CCCAAGUGGCGCUGGGAAG 6910 cccAAGuGGcGcuGGGAAGdTsdT sense
    1704-1723 6911 CUUCCCAGCGCCACUUGGG 6912 CUUCCcAGCGCcACUUGGGdTsdT antis
    1705-1724 6913 CCAAGUGGCGCUGGGAAGG 6914 ccAAGuGGcGcuGGGAAGGdTsdT sense
    1705-1724 6915 CCUUCCCAGCGCCACUUGG 6916 CCUUCCcAGCGCcACUUGGdTsdT antis
    1730-1749 6917 CAGCCCAUCAAGCUCCUGC 6918 cAGcccAucAAGcuccuGcdTsdT sense
    1730-1749 6919 GCAGGAGCUUGAUGGGCUG 6920 GcAGGAGCUUGAUGGGCUGdTsdT antis
    1753-1772 6921 GCUGGGCCCCUAGACUAGA 6922 GcuGGGccccuAGAcuAGAdTsdT sense
    1753-1772 6923 UCUAGUCUAGGGGCCCAGC 6924 UCuAGUCuAGGGGCCcAGCdTsdT antis
    1759-1778 6925 CCCCUAGACUAGAGGGCAG 6926 ccccuAGAcuAGAGGGcAGdTsdT sense
    1759-1778 6927 CUGCCCUCUAGUCUAGGGG 6928 CUGCCCUCuAGUCuAGGGGdTsdT antis
    1760-1779 6929 CCCUAGACUAGAGGGCAGA 6930 cccuAGAcuAGAGGGcAGAdTsdT sense
    1760-1779 6931 UCUGCCCUCUAGUCUAGGG 6932 UCUGCCCUCuAGUCuAGGGdTsdT antis
    1763-1782 6933 UAGACUAGAGGGCAGAGGU 6934 uAGAcuAGAGGGcAGAGGudTsdT sense
    1763-1782 6935 ACCUCUGCCCUCUAGUCUA 6936 ACCUCUGCCCUCuAGUCuAdTsdT antis
    1773-1792 6937 GGCAGAGGUAAAUGAACUA 6938 GGcAGAGGuAAAuGAAcuAdTsdT sense
    1773-1792 6939 UAGUUCAUUUACCUCUGCC 6940 uAGUUcAUUuACCUCUGCCdTsdT antis
    1774-1793 6941 GCAGAGGUAAAUGAACUAC 6942 GcAGAGGuAAAuGAAcuAcdTsdT sense
    1774-1793 6943 GUAGUUCAUUUACCUCUGC 6944 GuAGUUcAUUuACCUCUGCdTsdT antis
    1782-1801 6945 AAAUGAACUACCCCCAGCA 6946 AAAuGAAcuAcccccAGcAdTsdT sense
    1782-1801 6947 UGCUGGGGGUAGUUCAUUU 6948 UGCUGGGGGuAGUUcAUUUdTsdT antis
    1784-1803 6949 AUGAACUACCCCCAGCAUC 6950 AuGAAcuAcccccAGcAucdTsdT sense
    1784-1803 6951 GAUGCUGGGGGUAGUUCAU 6952 GAUGCUGGGGGuAGUUcAUdTsdT antis
    1785-1804 6953 UGAACUACCCCCAGCAUCU 6954 uGAAcuAcccccAGcAucudTsdT sense
    1785-1804 6955 AGAUGCUGGGGGUAGUUCA 6956 AGAUGCUGGGGGuAGUUcAdTsdT antis
    1790-1809 6957 UACCCCCAGCAUCUAGGCC 6958 uAcccccAGcAucuAGGccdTsdT sense
    1790-1809 6959 GGCCUAGAUGCUGGGGGUA 6960 GGCCuAGAUGCUGGGGGuAdTsdT antis
    1794-1813 6961 CCCAGCAUCUAGGCCUCCC 6962 cccAGcAucuAGGccucccdTsdT sense
    1794-1813 6963 GGGAGGCCUAGAUGCUGGG 6964 GGGAGGCCuAGAUGCUGGGdTsdT antis
    1795-1814 6965 CCAGCAUCUAGGCCUCCCU 6966 ccAGcAucuAGGccucccudTsdT sense
    1795-1814 6967 AGGGAGGCCUAGAUGCUGG 6968 AGGGAGGCCuAGAUGCUGGdTsdT antis
    1882-1901 6969 GGAAGGACGGGGUUUGGGG 6970 GGAAGGAcGGGGuuuGGGGdTsdT sense
    1882-1901 6971 CCCCAAACCCCGUCCUUCC 6972 CCCcAAACCCCGUCCUUCCdTsdT antis
    1883-1902 6973 GAAGGACGGGGUUUGGGGG 6974 GAAGGAcGGGGuuuGGGGGdTsdT sense
    1883-1902 6975 CCCCCAAACCCCGUCCUUC 6976 CCCCcAAACCCCGUCCUUCdTsdT antis
    1913-1932 6977 UCUACCCCCUUGGUCCCCU 6978 ucuAcccccuuGGuccccudTsdT sense
    1913-1932 6979 AGGGGACCAAGGGGGUAGA 6980 AGGGGACcAAGGGGGuAGAdTsdT antis
    68-87 6981 CGGAGCCGGAGCCCGAACG 6982 cGGAGccGGAGcccGAAcGdTsdT sense
    68-87 6983 CGUUCGGGCUCCGGCUCCG 6984 CGUUCGGGCUCCGGCUCCGdTsdT antis
    117-136 6985 GAGGCGGCGGCAGAGGCAG 6986 GAGGcGGcGGcAGAGGcAGdTsdT sense
    117-136 6987 CUGCCUCUGCCGCCGCCUC 6988 CUGCCUCUGCCGCCGCCUCdTsdT antis
    188-207 6989 CGCCAUGAGCGGCGGCGGG 6990 cGccAuGAGcGGcGGcGGGdTsdT sense
    188-207 6991 CCCGCCGCCGCUCAUGGCG 6992 CCCGCCGCCGCUcAUGGCGdTsdT antis
    219-238 6993 GGCCCUGGGGGCUCGGGCC 6994 GGcccuGGGGGcucGGGccdTsdT sense
    219-238 6995 GGCCCGAGCCCCCAGGGCC 6996 GGCCCGAGCCCCcAGGGCCdTsdT antis
    220-239 6997 GCCCUGGGGGCUCGGGCCG 6998 GcccuGGGGGcucGGGccGdTsdT sense
    220-239 6999 CGGCCCGAGCCCCCAGGGC 7000 CGGCCCGAGCCCCcAGGGCdTsdT antis
    233-252 7001 GGGCCGGGCGCGGACCAGC 7002 GGGccGGGcGcGGAccAGcdTsdT sense
    233-252 7003 GCUGGUCCGCGCCCGGCCC 7004 GCUGGUCCGCGCCCGGCCCdTsdT antis
    237-256 7005 CGGGCGCGGACCAGCUCGU 7006 cGGGcGcGGAccAGcucGudTsdT sense
    237-256 7007 ACGAGCUGGUCCGCGCCCG 7008 ACGAGCUGGUCCGCGCCCGdTsdT antis
    308-327 7009 GGCCUCUGGCCCAGGAGGC 7010 GGccucuGGcccAGGAGGcdTsdT sense
    308-327 7011 GCCUCCUGGGCCAGAGGCC 7012 GCCUCCUGGGCcAGAGGCCdTsdT antis
    311-330 7013 CUCUGGCCCAGGAGGCACU 7014 cucuGGcccAGGAGGcAcudTsdT sense
    311-330 7015 AGUGCCUCCUGGGCCAGAG 7016 AGUGCCUCCUGGGCcAGAGdTsdT antis
    351-370 7017 GGGGCUAUGGGUGGGGGCG 7018 GGGGcuAuGGGuGGGGGcGdTsdT sense
    351-370 7019 CGCCCCCACCCAUAGCCCC 7020 CGCCCCcACCcAuAGCCCCdTsdT antis
    353-372 7021 GGCUAUGGGUGGGGGCGUG 7022 GGcuAuGGGuGGGGGcGuGdTsdT sense
    353-372 7023 CACGCCCCCACCCAUAGCC 7024 cACGCCCCcACCcAuAGCCdTsdT antis
    355-374 7025 CUAUGGGUGGGGGCGUGGG 7026 cuAuGGGuGGGGGcGuGGGdTsdT sense
    355-374 7027 CCCACGCCCCCACCCAUAG 7028 CCcACGCCCCcACCcAuAGdTsdT antis
    357-376 7029 AUGGGUGGGGGCGUGGGAG 7030 AuGGGuGGGGGcGuGGGAGdTsdT sense
    357-376 7031 CUCCCACGCCCCCACCCAU 7032 CUCCcACGCCCCcACCcAUdTsdT antis
    361-380 7033 GUGGGGGCGUGGGAGCCUC 7034 GuGGGGGcGuGGGAGccucdTsdT sense
    361-380 7035 GAGGCUCCCACGCCCCCAC 7036 GAGGCUCCcACGCCCCcACdTsdT antis
    363-382 7037 GGGGGCGUGGGAGCCUCGA 7038 GGGGGcGuGGGAGccucGAdTsdT sense
    363-382 7039 UCGAGGCUCCCACGCCCCC 7040 UCGAGGCUCCcACGCCCCCdTsdT antis
    364-383 7041 GGGGCGUGGGAGCCUCGAG 7042 GGGGcGuGGGAGccucGAGdTsdT sense
    364-383 7043 CUCGAGGCUCCCACGCCCC 7044 CUCGAGGCUCCcACGCCCCdTsdT antis
    365-384 7045 GGGCGUGGGAGCCUCGAGC 7046 GGGcGuGGGAGccucGAGcdTsdT sense
    365-384 7047 GCUCGAGGCUCCCACGCCC 7048 GCUCGAGGCUCCcACGCCCdTsdT antis
    366-385 7049 GGCGUGGGAGCCUCGAGCU 7050 GGcGuGGGAGccucGAGcudTsdT sense
    366-385 7051 AGCUCGAGGCUCCCACGCC 7052 AGCUCGAGGCUCCcACGCCdTsdT antis
    368-387 7053 CGUGGGAGCCUCGAGCUCC 7054 cGuGGGAGccucGAGcuccdTsdT sense
    368-387 7055 GGAGCUCGAGGCUCCCACG 7056 GGAGCUCGAGGCUCCcACGdTsdT antis
    485-504 7057 GAAGGUGACCACAGUGGUA 7058 GAAGGuGAccAcAGuGGuAdTsdT sense
    485-504 7059 UACCACUGUGGUCACCUUC 7060 uACcACUGUGGUcACCUUCdTsdT antis
    487-506 7061 AGGUGACCACAGUGGUAGC 7062 AGGuGAccAcAGuGGuAGcdTsdT sense
    487-506 7063 GCUACCACUGUGGUCACCU 7064 GCuACcACUGUGGUcACCUdTsdT antis
    488-507 7065 GGUGACCACAGUGGUAGCC 7066 GGuGAccAcAGuGGuAGccdTsdT sense
    488-507 7067 GGCUACCACUGUGGUCACC 7068 GGCuACcACUGUGGUcACCdTsdT antis
    547-566 7069 ACACUGACAUCAAAGUGAU 7070 AcAcuGAcAucAAAGuGAudTsdT sense
    547-566 7071 AUCACUUUGAUGUCAGUGU 7072 AUcACUUUGAUGUcAGUGUdTsdT antis
    548-567 7073 CACUGACAUCAAAGUGAUU 7074 cAcuGAcAucAAAGuGAuudTsdT sense
    548-567 7075 AAUCACUUUGAUGUCAGUG 7076 AAUcACUUUGAUGUcAGUGdTsdT antis
    551-570 7077 UGACAUCAAAGUGAUUGGU 7078 uGAcAucAAAGuGAuuGGudTsdT sense
    551-570 7079 ACCAAUCACUUUGAUGUCA 7080 ACcAAUcACUUUGAUGUcAdTsdT antis
    552-571 7081 GACAUCAAAGUGAUUGGUA 7082 GAcAucAAAGuGAuuGGuAdTsdT sense
    552-571 7083 UACCAAUCACUUUGAUGUC 7084 uACcAAUcACUUUGAUGUCdTsdT antis
    553-572 7085 ACAUCAAAGUGAUUGGUAA 7086 AcAucAAAGuGAuuGGuAAdTsdT sense
    553-572 7087 UUACCAAUCACUUUGAUGU 7088 UuACcAAUcACUUUGAUGUdTsdT antis
    554-573 7089 CAUCAAAGUGAUUGGUAAU 7090 cAucAAAGuGAuuGGuAAudTsdT sense
    554-573 7091 AUUACCAAUCACUUUGAUG 7092 AUuACcAAUcACUUUGAUGdTsdT antis
    556-575 7093 UCAAAGUGAUUGGUAAUGG 7094 ucAAAGuGAuuGGuAAuGGdTsdT sense
    556-575 7095 CCAUUACCAAUCACUUUGA 7096 CcAUuACcAAUcACUUUGAdTsdT antis
    557-576 7097 CAAAGUGAUUGGUAAUGGC 7098 cAAAGuGAuuGGuAAuGGcdTsdT sense
    557-576 7099 GCCAUUACCAAUCACUUUG 7100 GCcAUuACcAAUcACUUUGdTsdT antis
    562-581 7101 UGAUUGGUAAUGGCUCAUU 7102 uGAuuGGuAAuGGcucAuudTsdT sense
    562-581 7103 AAUGAGCCAUUACCAAUCA 7104 AAUGAGCcAUuACcAAUcAdTsdT antis
    563-582 7105 GAUUGGUAAUGGCUCAUUC 7106 GAuuGGuAAuGGcucAuucdTsdT sense
    563-582 7107 GAAUGAGCCAUUACCAAUC 7108 GAAUGAGCcAUuACcAAUCdTsdT antis
    564-583 7109 AUUGGUAAUGGCUCAUUCG 7110 AuuGGuAAuGGcucAuucGdTsdT sense
    564-583 7111 CGAAUGAGCCAUUACCAAU 7112 CGAAUGAGCcAUuACcAAUdTsdT antis
    565-584 7113 UUGGUAAUGGCUCAUUCGG 7114 uuGGuAAuGGcucAuucGGdTsdT sense
    565-584 7115 CCGAAUGAGCCAUUACCAA 7116 CCGAAUGAGCcAUuACcAAdTsdT antis
    566-585 7117 UGGUAAUGGCUCAUUCGGA 7118 uGGuAAuGGcucAuucGGAdTsdT sense
    566-585 7119 UCCGAAUGAGCCAUUACCA 7120 UCCGAAUGAGCcAUuACcAdTsdT antis
    627-646 7121 GCCAUCAAGAAGGUUCUUC 7122 GccAucAAGAAGGuucuucdTsdT sense
    627-646 7123 GAAGAACCUUCUUGAUGGC 7124 GAAGAACCUUCUUGAUGGCdTsdT antis
    631-650 7125 UCAAGAAGGUUCUUCAGGA 7126 ucAAGAAGGuucuucAGGAdTsdT sense
    631-650 7127 UCCUGAAGAACCUUCUUGA 7128 UCCUGAAGAACCUUCUUGAdTsdT antis
    632-651 7129 CAAGAAGGUUCUUCAGGAC 7130 cAAGAAGGuucuucAGGAcdTsdT sense
    632-651 7131 GUCCUGAAGAACCUUCUUG 7132 GUCCUGAAGAACCUUCUUGdTsdT antis
    634-653 7133 AGAAGGUUCUUCAGGACAA 7134 AGAAGGuucuucAGGAcAAdTsdT sense
    634-653 7135 UUGUCCUGAAGAACCUUCU 7136 UUGUCCUGAAGAACCUUCUdTsdT antis
    635-654 7137 GAAGGUUCUUCAGGACAAA 7138 GAAGGuucuucAGGAcAAAdTsdT sense
    635-654 7139 UUUGUCCUGAAGAACCUUC 7140 UUUGUCCUGAAGAACCUUCdTsdT antis
    638-657 7141 GGUUCUUCAGGACAAAAGG 7142 GGuucuucAGGAcAAAAGGdTsdT sense
    638-657 7143 CCUUUUGUCCUGAAGAACC 7144 CCUUUUGUCCUGAAGAACCdTsdT antis
    639-658 7145 GUUCUUCAGGACAAAAGGU 7146 GuucuucAGGAcAAAAGGudTsdT sense
    639-658 7147 ACCUUUUGUCCUGAAGAAC 7148 ACCUUUUGUCCUGAAGAACdTsdT antis
    640-659 7149 UUCUUCAGGACAAAAGGUU 7150 uucuucAGGAcAAAAGGuudTsdT sense
    640-659 7151 AACCUUUUGUCCUGAAGAA 7152 AACCUUUUGUCCUGAAGAAdTsdT antis
    641-660 7153 UCUUCAGGACAAAAGGUUC 7154 ucuucAGGAcAAAAGGuucdTsdT sense
    641-660 7155 GAACCUUUUGUCCUGAAGA 7156 GAACCUUUUGUCCUGAAGAdTsdT antis
    642-661 7157 CUUCAGGACAAAAGGUUCA 7158 cuucAGGAcAAAAGGuucAdTsdT sense
    642-661 7159 UGAACCUUUUGUCCUGAAG 7160 UGAACCUUUUGUCCUGAAGdTsdT antis
    643-662 7161 UUCAGGACAAAAGGUUCAA 7162 uucAGGAcAAAAGGuucAAdTsdT sense
    643-662 7163 UUGAACCUUUUGUCCUGAA 7164 UUGAACCUUUUGUCCUGAAdTsdT antis
    644-663 7165 UCAGGACAAAAGGUUCAAG 7166 ucAGGAcAAAAGGuucAAGdTsdT sense
    644-663 7167 CUUGAACCUUUUGUCCUGA 7168 CUUGAACCUUUUGUCCUGAdTsdT antis
    645-664 7169 CAGGACAAAAGGUUCAAGA 7170 cAGGAcAAAAGGuucAAGAdTsdT sense
    645-664 7171 UCUUGAACCUUUUGUCCUG 7172 UCUUGAACCUUUUGUCCUGdTsdT antis
    686-705 7173 UAAGCUGGACCACUGCAAU 7174 uAAGcuGGAccAcuGcAAudTsdT sense
    686-705 7175 AUUGCAGUGGUCCAGCUUA 7176 AUUGcAGUGGUCcAGCUuAdTsdT antis
    687-706 7177 AAGCUGGACCACUGCAAUA 7178 AAGcuGGAccAcuGcAAuAdTsdT sense
    687-706 7179 UAUUGCAGUGGUCCAGCUU 7180 uAUUGcAGUGGUCcAGCUUdTsdT antis
    689-708 7181 GCUGGACCACUGCAAUAUU 7182 GcuGGAccAcuGcAAuAuudTsdT sense
    689-708 7183 AAUAUUGCAGUGGUCCAGC 7184 AAuAUUGcAGUGGUCcAGCdTsdT antis
    690-709 7185 CUGGACCACUGCAAUAUUG 7186 cuGGAccAcuGcAAuAuuGdTsdT sense
    690-709 7187 CAAUAUUGCAGUGGUCCAG 7188 cAAuAUUGcAGUGGUCcAGdTsdT antis
    691-710 7189 UGGACCACUGCAAUAUUGU 7190 uGGAccAcuGcAAuAuuGudTsdT sense
    691-710 7191 ACAAUAUUGCAGUGGUCCA 7192 AcAAuAUUGcAGUGGUCcAdTsdT antis
    692-711 7193 GGACCACUGCAAUAUUGUG 7194 GGAccAcuGcAAuAuuGuGdTsdT sense
    692-711 7195 CACAAUAUUGCAGUGGUCC 7196 cAcAAuAUUGcAGUGGUCCdTsdT antis
    694-713 7197 ACCACUGCAAUAUUGUGAG 7198 AccAcuGcAAuAuuGuGAGdTsdT sense
    694-713 7199 CUCACAAUAUUGCAGUGGU 7200 CUcAcAAuAUUGcAGUGGUdTsdT antis
    696-715 7201 CACUGCAAUAUUGUGAGGC 7202 cAcuGcAAuAuuGuGAGGcdTsdT sense
    696-715 7203 GCCUCACAAUAUUGCAGUG 7204 GCCUcAcAAuAUUGcAGUGdTsdT antis
    698-717 7205 CUGCAAUAUUGUGAGGCUG 7206 cuGcAAuAuuGuGAGGcuGdTsdT sense
    698-717 7207 CAGCCUCACAAUAUUGCAG 7208 cAGCCUcAcAAuAUUGcAGdTsdT antis
    699-718 7209 UGCAAUAUUGUGAGGCUGC 7210 uGcAAuAuuGuGAGGcuGcdTsdT sense
    699-718 7211 GCAGCCUCACAAUAUUGCA 7212 GcAGCCUcAcAAuAUUGcAdTsdT antis
    718-737 7213 GGUACUUUUUCUACUCCAG 7214 GGuAcuuuuucuAcuccAGdTsdT sense
    718-737 7215 CUGGAGUAGAAAAAGUACC 7216 CUGGAGuAGAAAAAGuACCdTsdT antis
    720-739 7217 UACUUUUUCUACUCCAGUG 7218 uAcuuuuucuAcuccAGuGdTsdT sense
    720-739 7219 CACUGGAGUAGAAAAAGUA 7220 cACUGGAGuAGAAAAAGuAdTsdT antis
    721-740 7221 ACUUUUUCUACUCCAGUGG 7222 AcuuuuucuAcuccAGuGGdTsdT sense
    721-740 7223 CCACUGGAGUAGAAAAAGU 7224 CcACUGGAGuAGAAAAAGUdTsdT antis
    723-742 7225 UUUUUCUACUCCAGUGGGG 7226 uuuuucuAcuccAGuGGGGdTsdT sense
    723-742 7227 CCCCACUGGAGUAGAAAAA 7228 CCCcACUGGAGuAGAAAAAdTsdT antis
    729-748 7229 UACUCCAGUGGGGAGAAGA 7230 uAcuccAGuGGGGAGAAGAdTsdT sense
    729-748 7231 UCUUCUCCCCACUGGAGUA 7232 UCUUCUCCCcACUGGAGuAdTsdT antis
    730-749 7233 ACUCCAGUGGGGAGAAGAA 7234 AcuccAGuGGGGAGAAGAAdTsdT sense
    730-749 7235 UUCUUCUCCCCACUGGAGU 7236 UUCUUCUCCCcACUGGAGUdTsdT antis
    736-755 7237 GUGGGGAGAAGAAGGACGA 7238 GuGGGGAGAAGAAGGAcGAdTsdT sense
    736-755 7239 UCGUCCUUCUUCUCCCCAC 7240 UCGUCCUUCUUCUCCCcACdTsdT antis
    737-756 7241 UGGGGAGAAGAAGGACGAG 7242 uGGGGAGAAGAAGGAcGAGdTsdT sense
    737-756 7243 CUCGUCCUUCUUCUCCCCA 7244 CUCGUCCUUCUUCUCCCcAdTsdT antis
    755-774 7245 GCUGUAUUUGAAUCUGGUG 7246 GcuGuAuuuGAAucuGGuGdTsdT sense
    755-774 7247 CACCAGAUUCAAAUACAGC 7248 cACcAGAUUcAAAuAcAGCdTsdT antis
    756-775 7249 CUGUAUUUGAAUCUGGUGC 7250 cuGuAuuuGAAucuGGuGcdTsdT sense
    756-775 7251 GCACCAGAUUCAAAUACAG 7252 GcACcAGAUUcAAAuAcAGdTsdT antis
    758-777 7253 GUAUUUGAAUCUGGUGCUG 7254 GuAuuuGAAucuGGuGcuGdTsdT sense
    758-777 7255 CAGCACCAGAUUCAAAUAC 7256 cAGcACcAGAUUcAAAuACdTsdT antis
    761-780 7257 UUUGAAUCUGGUGCUGGAG 7258 uuuGAAucuGGuGcuGGAGdTsdT sense
    761-780 7259 CUCCAGCACCAGAUUCAAA 7260 CUCcAGcACcAGAUUcAAAdTsdT antis
    765-784 7261 AAUCUGGUGCUGGAGUAUG 7262 AAucuGGuGcuGGAGuAuGdTsdT sense
    765-784 7263 CAUACUCCAGCACCAGAUU 7264 cAuACUCcAGcACcAGAUUdTsdT antis
    769-788 7265 UGGUGCUGGAGUAUGUGCC 7266 uGGuGcuGGAGuAuGuGccdTsdT sense
    769-788 7267 GGCACAUACUCCAGCACCA 7268 GGcAcAuACUCcAGcACcAdTsdT antis
    770-789 7269 GGUGCUGGAGUAUGUGCCC 7270 GGuGcuGGAGuAuGuGcccdTsdT sense
    770-789 7271 GGGCACAUACUCCAGCACC 7272 GGGcAcAuACUCcAGcACCdTsdT antis
    771-790 7273 GUGCUGGAGUAUGUGCCCG 7274 GuGcuGGAGuAuGuGcccGdTsdT sense
    771-790 7275 CGGGCACAUACUCCAGCAC 7276 CGGGcAcAuACUCcAGcACdTsdT antis
    772-791 7277 UGCUGGAGUAUGUGCCCGA 7278 uGcuGGAGuAuGuGcccGAdTsdT sense
    772-791 7279 UCGGGCACAUACUCCAGCA 7280 UCGGGcAcAuACUCcAGcAdTsdT antis
    773-792 7281 GCUGGAGUAUGUGCCCGAG 7282 GcuGGAGuAuGuGcccGAGdTsdT sense
    773-792 7283 CUCGGGCACAUACUCCAGC 7284 CUCGGGcAcAuACUCcAGCdTsdT antis
    774-793 7285 CUGGAGUAUGUGCCCGAGA 7286 cuGGAGuAuGuGcccGAGAdTsdT sense
    774-793 7287 UCUCGGGCACAUACUCCAG 7288 UCUCGGGcAcAuACUCcAGdTsdT antis
    781-800 7289 AUGUGCCCGAGACGGUGUA 7290 AuGuGcccGAGAcGGuGuAdTsdT sense
    781-800 7291 UACACCGUCUCGGGCACAU 7292 uAcACCGUCUCGGGcAcAUdTsdT antis
    782-801 7293 UGUGCCCGAGACGGUGUAC 7294 uGuGcccGAGAcGGuGuAcdTsdT sense
    782-801 7295 GUACACCGUCUCGGGCACA 7296 GuAcACCGUCUCGGGcAcAdTsdT antis
    803-822 7297 AGUGGCCCGCCACUUCACC 7298 AGuGGcccGccAcuucAccdTsdT sense
    803-822 7299 GGUGAAGUGGCGGGCCACU 7300 GGUGAAGUGGCGGGCcACUdTsdT antis
    804-823 7301 GUGGCCCGCCACUUCACCA 7302 GuGGcccGccAcuucAccAdTsdT sense
    804-823 7303 UGGUGAAGUGGCGGGCCAC 7304 UGGUGAAGUGGCGGGCcACdTsdT antis
    805-824 7305 UGGCCCGCCACUUCACCAA 7306 uGGcccGccAcuucAccAAdTsdT sense
    805-824 7307 UUGGUGAAGUGGCGGGCCA 7308 UUGGUGAAGUGGCGGGCcAdTsdT antis
    806-825 7309 GGCCCGCCACUUCACCAAG 7310 GGcccGccAcuucAccAAGdTsdT sense
    806-825 7311 CUUGGUGAAGUGGCGGGCC 7312 CUUGGUGAAGUGGCGGGCCdTsdT antis
    807-826 7313 GCCCGCCACUUCACCAAGG 7314 GcccGccAcuucAccAAGGdTsdT sense
    807-826 7315 CCUUGGUGAAGUGGCGGGC 7316 CCUUGGUGAAGUGGCGGGCdTsdT antis
    808-827 7317 CCCGCCACUUCACCAAGGC 7318 cccGccAcuucAccAAGGcdTsdT sense
    808-827 7319 GCCUUGGUGAAGUGGCGGG 7320 GCCUUGGUGAAGUGGCGGGdTsdT antis
    809-828 7321 CCGCCACUUCACCAAGGCC 7322 ccGccAcuucAccAAGGccdTsdT sense
    809-828 7323 GGCCUUGGUGAAGUGGCGG 7324 GGCCUUGGUGAAGUGGCGGdTsdT antis
    810-829 7325 CGCCACUUCACCAAGGCCA 7326 cGccAcuucAccAAGGccAdTsdT sense
    810-829 7327 UGGCCUUGGUGAAGUGGCG 7328 UGGCCUUGGUGAAGUGGCGdTsdT antis
    811-830 7329 GCCACUUCACCAAGGCCAA 7330 GccAcuucAccAAGGccAAdTsdT sense
    811-830 7331 UUGGCCUUGGUGAAGUGGC 7332 UUGGCCUUGGUGAAGUGGCdTsdT antis
    813-832 7333 CACUUCACCAAGGCCAAGC 7334 cAcuucAccAAGGccAAGcdTsdT sense
    813-832 7335 GCUUGGCCUUGGUGAAGUG 7336 GCUUGGCCUUGGUGAAGUGdTsdT antis
    815-834 7337 CUUCACCAAGGCCAAGCUG 7338 cuucAccAAGGccAAGcuGdTsdT sense
    815-834 7339 CAGCUUGGCCUUGGUGAAG 7340 cAGCUUGGCCUUGGUGAAGdTsdT antis
    817-836 7341 UCACCAAGGCCAAGCUGAU 7342 ucAccAAGGccAAGcuGAudTsdT sense
    817-836 7343 AUCAGCUUGGCCUUGGUGA 7344 AUcAGCUUGGCCUUGGUGAdTsdT antis
    858-877 7345 GUGUACAUGUACCAGCUCU 7346 GuGuAcAuGuAccAGcucudTsdT sense
    858-877 7347 AGAGCUGGUACAUGUACAC 7348 AGAGCUGGuAcAUGuAcACdTsdT antis
    860-879 7349 GUACAUGUACCAGCUCUUC 7350 GuAcAuGuAccAGcucuucdTsdT sense
    860-879 7351 GAAGAGCUGGUACAUGUAC 7352 GAAGAGCUGGuAcAUGuACdTsdT antis
    861-880 7353 UACAUGUACCAGCUCUUCC 7354 uAcAuGuAccAGcucuuccdTsdT sense
    861-880 7355 GGAAGAGCUGGUACAUGUA 7356 GGAAGAGCUGGuAcAUGuAdTsdT antis
    862-881 7357 ACAUGUACCAGCUCUUCCG 7358 AcAuGuAccAGcucuuccGdTsdT sense
    862-881 7359 CGGAAGAGCUGGUACAUGU 7360 CGGAAGAGCUGGuAcAUGUdTsdT antis
    863-882 7361 CAUGUACCAGCUCUUCCGG 7362 cAuGuAccAGcucuuccGGdTsdT sense
    863-882 7363 CCGGAAGAGCUGGUACAUG 7364 CCGGAAGAGCUGGuAcAUGdTsdT antis
    865-884 7365 UGUACCAGCUCUUCCGGAG 7366 uGuAccAGcucuuccGGAGdTsdT sense
    865-884 7367 CUCCGGAAGAGCUGGUACA 7368 CUCCGGAAGAGCUGGuAcAdTsdT antis
    866-885 7369 GUACCAGCUCUUCCGGAGC 7370 GuAccAGcucuuccGGAGcdTsdT sense
    866-885 7371 GCUCCGGAAGAGCUGGUAC 7372 GCUCCGGAAGAGCUGGuACdTsdT antis
    867-886 7373 UACCAGCUCUUCCGGAGCU 7374 uAccAGcucuuccGGAGcudTsdT sense
    867-886 7375 AGCUCCGGAAGAGCUGGUA 7376 AGCUCCGGAAGAGCUGGuAdTsdT antis
    868-887 7377 ACCAGCUCUUCCGGAGCUU 7378 AccAGcucuuccGGAGcuudTsdT sense
    868-887 7379 AAGCUCCGGAAGAGCUGGU 7380 AAGCUCCGGAAGAGCUGGUdTsdT antis
    869-888 7381 CCAGCUCUUCCGGAGCUUG 7382 ccAGcucuuccGGAGcuuGdTsdT sense
    869-888 7383 CAAGCUCCGGAAGAGCUGG 7384 cAAGCUCCGGAAGAGCUGGdTsdT antis
    870-889 7385 CAGCUCUUCCGGAGCUUGG 7386 cAGcucuuccGGAGcuuGGdTsdT sense
    870-889 7387 CCAAGCUCCGGAAGAGCUG 7388 CcAAGCUCCGGAAGAGCUGdTsdT antis
    871-890 7389 AGCUCUUCCGGAGCUUGGC 7390 AGcucuuccGGAGcuuGGcdTsdT sense
    871-890 7391 GCCAAGCUCCGGAAGAGCU 7392 GCcAAGCUCCGGAAGAGCUdTsdT antis
    872-891 7393 GCUCUUCCGGAGCUUGGCC 7394 GcucuuccGGAGcuuGGccdTsdT sense
    872-891 7395 GGCCAAGCUCCGGAAGAGC 7396 GGCcAAGCUCCGGAAGAGCdTsdT antis
    874-893 7397 UCUUCCGGAGCUUGGCCUA 7398 ucuuccGGAGcuuGGccuAdTsdT sense
    874-893 7399 UAGGCCAAGCUCCGGAAGA 7400 uAGGCcAAGCUCCGGAAGAdTsdT antis
    876-895 7401 UUCCGGAGCUUGGCCUACA 7402 uuccGGAGcuuGGccuAcAdTsdT sense
    876-895 7403 UGUAGGCCAAGCUCCGGAA 7404 UGuAGGCcAAGCUCCGGAAdTsdT antis
    877-896 7405 UCCGGAGCUUGGCCUACAU 7406 uccGGAGcuuGGccuAcAudTsdT sense
    877-896 7407 AUGUAGGCCAAGCUCCGGA 7408 AUGuAGGCcAAGCUCCGGAdTsdT antis
    878-897 7409 CCGGAGCUUGGCCUACAUC 7410 ccGGAGcuuGGccuAcAucdTsdT sense
    878-897 7411 GAUGUAGGCCAAGCUCCGG 7412 GAUGuAGGCcAAGCUCCGGdTsdT antis
    911-930 7413 GUGUCACCGUGACAUCAAG 7414 GuGucAccGuGAcAucAAGdTsdT sense
    911-930 7415 CUUGAUGUCACGGUGACAC 7416 CUUGAUGUcACGGUGAcACdTsdT antis
    935-954 7417 GAAUUUGCUUGUGGACCCU 7418 GAAuuuGcuuGuGGAcccudTsdT sense
    935-954 7419 AGGGUCCACAAGCAAAUUC 7420 AGGGUCcAcAAGcAAAUUCdTsdT antis
    939-958 7421 UUGCUUGUGGACCCUGACA 7422 uuGcuuGuGGAcccuGAcAdTsdT sense
    939-958 7423 UGUCAGGGUCCACAAGCAA 7424 UGUcAGGGUCcAcAAGcAAdTsdT antis
    940-959 7425 UGCUUGUGGACCCUGACAC 7426 uGcuuGuGGAcccuGAcAcdTsdT sense
    940-959 7427 GUGUCAGGGUCCACAAGCA 7428 GUGUcAGGGUCcAcAAGcAdTsdT antis
    941-960 7429 GCUUGUGGACCCUGACACU 7430 GcuuGuGGAcccuGAcAcudTsdT sense
    941-960 7431 AGUGUCAGGGUCCACAAGC 7432 AGUGUcAGGGUCcAcAAGCdTsdT antis
    943-962 7433 UUGUGGACCCUGACACUGC 7434 uuGuGGAcccuGAcAcuGcdTsdT sense
    943-962 7435 GCAGUGUCAGGGUCCACAA 7436 GcAGUGUcAGGGUCcAcAAdTsdT antis
    949-968 7437 ACCCUGACACUGCUGUCCU 7438 AcccuGAcAcuGcuGuccudTsdT sense
    949-968 7439 AGGACAGCAGUGUCAGGGU 7440 AGGAcAGcAGUGUcAGGGUdTsdT antis
    952-971 7441 CUGACACUGCUGUCCUCAA 7442 cuGAcAcuGcuGuccucAAdTsdT sense
    952-971 7443 UUGAGGACAGCAGUGUCAG 7444 UUGAGGAcAGcAGUGUcAGdTsdT antis
    970-989 7445 AGCUCUGCGAUUUUGGCAG 7446 AGcucuGcGAuuuuGGcAGdTsdT sense
    970-989 7447 CUGCCAAAAUCGCAGAGCU 7448 CUGCcAAAAUCGcAGAGCUdTsdT antis
    974-993 7449 CUGCGAUUUUGGCAGUGCA 7450 cuGcGAuuuuGGcAGuGcAdTsdT sense
    974-993 7451 UGCACUGCCAAAAUCGCAG 7452 UGcACUGCcAAAAUCGcAGdTsdT antis
    977-996 7453 CGAUUUUGGCAGUGCAAAG 7454 cGAuuuuGGcAGuGcAAAGdTsdT sense
    977-996 7455 CUUUGCACUGCCAAAAUCG 7456 CUUUGcACUGCcAAAAUCGdTsdT antis
    978-997 7457 GAUUUUGGCAGUGCAAAGC 7458 GAuuuuGGcAGuGcAAAGcdTsdT sense
    978-997 7459 GCUUUGCACUGCCAAAAUC 7460 GCUUUGcACUGCcAAAAUCdTsdT antis
     986-1005 7461 CAGUGCAAAGCAGCUGGUU 7462 cAGuGcAAAGcAGcuGGuudTsdT sense
     986-1005 7463 AACCAGCUGCUUUGCACUG 7464 AACcAGCUGCUUUGcACUGdTsdT antis
     987-1006 7465 AGUGCAAAGCAGCUGGUUC 7466 AGuGcAAAGcAGcuGGuucdTsdT sense
     987-1006 7467 GAACCAGCUGCUUUGCACU 7468 GAACcAGCUGCUUUGcACUdTsdT antis
     988-1007 7469 GUGCAAAGCAGCUGGUUCG 7470 GuGcAAAGcAGcuGGuucGdTsdT sense
     988-1007 7471 CGAACCAGCUGCUUUGCAC 7472 CGAACcAGCUGCUUUGcACdTsdT antis
    1162-1181 7473 GUGGGGUGGACCAGCUUGU 7474 GuGGGGuGGAccAGcuuGudTsdT sense
    1162-1181 7475 ACAAGCUGGUCCACCCCAC 7476 AcAAGCUGGUCcACCCcACdTsdT antis
    1163-1182 7477 UGGGGUGGACCAGCUUGUG 7478 uGGGGuGGAccAGcuuGuGdTsdT sense
    1163-1182 7479 CACAAGCUGGUCCACCCCA 7480 cAcAAGCUGGUCcACCCcAdTsdT antis
    1164-1183 7481 GGGGUGGACCAGCUUGUGG 7482 GGGGuGGAccAGcuuGuGGdTsdT sense
    1164-1183 7483 CCACAAGCUGGUCCACCCC 7484 CcAcAAGCUGGUCcACCCCdTsdT antis
    1165-1184 7485 GGGUGGACCAGCUUGUGGA 7486 GGGuGGAccAGcuuGuGGAdTsdT sense
    1165-1184 7487 UCCACAAGCUGGUCCACCC 7488 UCcAcAAGCUGGUCcACCCdTsdT antis
    1168-1187 7489 UGGACCAGCUUGUGGAGAU 7490 uGGAccAGcuuGuGGAGAudTsdT sense
    1168-1187 7491 AUCUCCACAAGCUGGUCCA 7492 AUCUCcAcAAGCUGGUCcAdTsdT antis
    1172-1191 7493 CCAGCUUGUGGAGAUCAUC 7494 ccAGcuuGuGGAGAucAucdTsdT sense
    1172-1191 7495 GAUGAUCUCCACAAGCUGG 7496 GAUGAUCUCcAcAAGCUGGdTsdT antis
    1173-1192 7497 CAGCUUGUGGAGAUCAUCA 7498 cAGcuuGuGGAGAucAucAdTsdT sense
    1173-1192 7499 UGAUGAUCUCCACAAGCUG 7500 UGAUGAUCUCcAcAAGCUGdTsdT antis
    1175-1194 7501 GCUUGUGGAGAUCAUCAAG 7502 GcuuGuGGAGAucAucAAGdTsdT sense
    1175-1194 7503 CUUGAUGAUCUCCACAAGC 7504 CUUGAUGAUCUCcAcAAGCdTsdT antis
    1176-1195 7505 CUUGUGGAGAUCAUCAAGG 7506 cuuGuGGAGAucAucAAGGdTsdT sense
    1176-1195 7507 CCUUGAUGAUCUCCACAAG 7508 CCUUGAUGAUCUCcAcAAGdTsdT antis
    1177-1196 7509 UUGUGGAGAUCAUCAAGGU 7510 uuGuGGAGAucAucAAGGudTsdT sense
    1177-1196 7511 ACCUUGAUGAUCUCCACAA 7512 ACCUUGAUGAUCUCcAcAAdTsdT antis
    1179-1198 7513 GUGGAGAUCAUCAAGGUAC 7514 GuGGAGAucAucAAGGuAcdTsdT sense
    1179-1198 7515 GUACCUUGAUGAUCUCCAC 7516 GuACCUUGAUGAUCUCcACdTsdT antis
    1180-1199 7517 UGGAGAUCAUCAAGGUACU 7518 uGGAGAucAucAAGGuAcudTsdT sense
    1180-1199 7519 AGUACCUUGAUGAUCUCCA 7520 AGuACCUUGAUGAUCUCcAdTsdT antis
    1181-1200 7521 GGAGAUCAUCAAGGUACUA 7522 GGAGAucAucAAGGuAcuAdTsdT sense
    1181-1200 7523 UAGUACCUUGAUGAUCUCC 7524 uAGuACCUUGAUGAUCUCCdTsdT antis
    1182-1201 7525 GAGAUCAUCAAGGUACUAG 7526 GAGAucAucAAGGuAcuAGdTsdT sense
    1182-1201 7527 CUAGUACCUUGAUGAUCUC 7528 CuAGuACCUUGAUGAUCUCdTsdT antis
    1184-1203 7529 GAUCAUCAAGGUACUAGGA 7530 GAucAucAAGGuAcuAGGAdTsdT sense
    1184-1203 7531 UCCUAGUACCUUGAUGAUC 7532 UCCuAGuACCUUGAUGAUCdTsdT antis
    1186-1205 7533 UCAUCAAGGUACUAGGAAC 7534 ucAucAAGGuAcuAGGAAcdTsdT sense
    1186-1205 7535 GUUCCUAGUACCUUGAUGA 7536 GUUCCuAGuACCUUGAUGAdTsdT antis
    1187-1206 7537 CAUCAAGGUACUAGGAACG 7538 cAucAAGGuAcuAGGAAcGdTsdT sense
    1187-1206 7539 CGUUCCUAGUACCUUGAUG 7540 CGUUCCuAGuACCUUGAUGdTsdT antis
    1205-1224 7541 GCCAACCAGGGAACAAAUC 7542 GccAAccAGGGAAcAAAucdTsdT sense
    1205-1224 7543 GAUUUGUUCCCUGGUUGGC 7544 GAUUUGUUCCCUGGUUGGCdTsdT antis
    1207-1226 7545 CAACCAGGGAACAAAUCCG 7546 cAAccAGGGAAcAAAuccGdTsdT sense
    1207-1226 7547 CGGAUUUGUUCCCUGGUUG 7548 CGGAUUUGUUCCCUGGUUGdTsdT antis
    1209-1228 7549 ACCAGGGAACAAAUCCGAG 7550 AccAGGGAAcAAAuccGAGdTsdT sense
    1209-1228 7551 CUCGGAUUUGUUCCCUGGU 7552 CUCGGAUUUGUUCCCUGGUdTsdT antis
    1212-1231 7553 AGGGAACAAAUCCGAGAGA 7554 AGGGAAcAAAuccGAGAGAdTsdT sense
    1212-1231 7555 UCUCUCGGAUUUGUUCCCU 7556 UCUCUCGGAUUUGUUCCCUdTsdT antis
    1214-1233 7557 GGAACAAAUCCGAGAGAUG 7558 GGAAcAAAuccGAGAGAuGdTsdT sense
    1214-1233 7559 CAUCUCUCGGAUUUGUUCC 7560 cAUCUCUCGGAUUUGUUCCdTsdT antis
    1219-1238 7561 AAAUCCGAGAGAUGAACCC 7562 AAAuccGAGAGAuGAAcccdTsdT sense
    1219-1238 7563 GGGUUCAUCUCUCGGAUUU 7564 GGGUUcAUCUCUCGGAUUUdTsdT antis
    1222-1241 7565 UCCGAGAGAUGAACCCUAA 7566 uccGAGAGAuGAAcccuAAdTsdT sense
    1222-1241 7567 UUAGGGUUCAUCUCUCGGA 7568 UuAGGGUUcAUCUCUCGGAdTsdT antis
    1223-1242 7569 CCGAGAGAUGAACCCUAAC 7570 ccGAGAGAuGAAcccuAAcdTsdT sense
    1223-1242 7571 GUUAGGGUUCAUCUCUCGG 7572 GUuAGGGUUcAUCUCUCGGdTsdT antis
    1247-1266 7573 GGAGUUCAAGUUCCCCCAG 7574 GGAGuucAAGuucccccAGdTsdT sense
    1247-1266 7575 CUGGGGGAACUUGAACUCC 7576 CUGGGGGAACUUGAACUCCdTsdT antis
    1248-1267 7577 GAGUUCAAGUUCCCCCAGA 7578 GAGuucAAGuucccccAGAdTsdT sense
    1248-1267 7579 UCUGGGGGAACUUGAACUC 7580 UCUGGGGGAACUUGAACUCdTsdT antis
    1249-1268 7581 AGUUCAAGUUCCCCCAGAU 7582 AGuucAAGuucccccAGAudTsdT sense
    1249-1268 7583 AUCUGGGGGAACUUGAACU 7584 AUCUGGGGGAACUUGAACUdTsdT antis
    1250-1269 7585 GUUCAAGUUCCCCCAGAUC 7586 GuucAAGuucccccAGAucdTsdT sense
    1250-1269 7587 GAUCUGGGGGAACUUGAAC 7588 GAUCUGGGGGAACUUGAACdTsdT antis
    1251-1270 7589 UUCAAGUUCCCCCAGAUCA 7590 uucAAGuucccccAGAucAdTsdT sense
    1251-1270 7591 UGAUCUGGGGGAACUUGAA 7592 UGAUCUGGGGGAACUUGAAdTsdT antis
    1252-1271 7593 UCAAGUUCCCCCAGAUCAA 7594 ucAAGuucccccAGAucAAdTsdT sense
    1252-1271 7595 UUGAUCUGGGGGAACUUGA 7596 UUGAUCUGGGGGAACUUGAdTsdT antis
    1253-1272 7597 CAAGUUCCCCCAGAUCAAA 7598 cAAGuucccccAGAucAAAdTsdT sense
    1253-1272 7599 UUUGAUCUGGGGGAACUUG 7600 UUUGAUCUGGGGGAACUUGdTsdT antis
    1255-1274 7601 AGUUCCCCCAGAUCAAAGC 7602 AGuucccccAGAucAAAGcdTsdT sense
    1255-1274 7603 GCUUUGAUCUGGGGGAACU 7604 GCUUUGAUCUGGGGGAACUdTsdT antis
    1257-1276 7605 UUCCCCCAGAUCAAAGCUC 7606 uucccccAGAucAAAGcucdTsdT sense
    1257-1276 7607 GAGCUUUGAUCUGGGGGAA 7608 GAGCUUUGAUCUGGGGGAAdTsdT antis
    1258-1277 7609 UCCCCCAGAUCAAAGCUCA 7610 ucccccAGAucAAAGcucAdTsdT sense
    1258-1277 7611 UGAGCUUUGAUCUGGGGGA 7612 UGAGCUUUGAUCUGGGGGAdTsdT antis
    1261-1280 7613 CCCAGAUCAAAGCUCACCC 7614 cccAGAucAAAGcucAcccdTsdT sense
    1261-1280 7615 GGGUGAGCUUUGAUCUGGG 7616 GGGUGAGCUUUGAUCUGGGdTsdT antis
    1262-1281 7617 CCAGAUCAAAGCUCACCCU 7618 ccAGAucAAAGcucAcccudTsdT sense
    1262-1281 7619 AGGGUGAGCUUUGAUCUGG 7620 AGGGUGAGCUUUGAUCUGGdTsdT antis
    1280-1299 7621 UUGGACAAAGGUGUUCAAA 7622 uuGGAcAAAGGuGuucAAAdTsdT sense
    1280-1299 7623 UUUGAACACCUUUGUCCAA 7624 UUUGAAcACCUUUGUCcAAdTsdT antis
    1282-1301 7625 GGACAAAGGUGUUCAAAUC 7626 GGAcAAAGGuGuucAAAucdTsdT sense
    1282-1301 7627 GAUUUGAACACCUUUGUCC 7628 GAUUUGAAcACCUUUGUCCdTsdT antis
    1283-1302 7629 GACAAAGGUGUUCAAAUCU 7630 GAcAAAGGuGuucAAAucudTsdT sense
    1283-1302 7631 AGAUUUGAACACCUUUGUC 7632 AGAUUUGAAcACCUUUGUCdTsdT antis
    1284-1303 7633 ACAAAGGUGUUCAAAUCUU 7634 AcAAAGGuGuucAAAucuudTsdT sense
    1284-1303 7635 AAGAUUUGAACACCUUUGU 7636 AAGAUUUGAAcACCUUUGUdTsdT antis
    1354-1373 7637 CGCCAUCCUCAAGGCUCUC 7638 cGccAuccucAAGGcucucdTsdT sense
    1354-1373 7639 GAGAGCCUUGAGGAUGGCG 7640 GAGAGCCUUGAGGAUGGCGdTsdT antis
    1361-1380 7641 CUCAAGGCUCUCCCCACUC 7642 cucAAGGcucuccccAcucdTsdT sense
    1361-1380 7643 GAGUGGGGAGAGCCUUGAG 7644 GAGUGGGGAGAGCCUUGAGdTsdT antis
    1379-1398 7645 CGAGGCUUGUGCCCACAGC 7646 cGAGGcuuGuGcccAcAGcdTsdT sense
    1379-1398 7647 GCUGUGGGCACAAGCCUCG 7648 GCUGUGGGcAcAAGCCUCGdTsdT antis
    1380-1399 7649 GAGGCUUGUGCCCACAGCU 7650 GAGGcuuGuGcccAcAGcudTsdT sense
    1380-1399 7651 AGCUGUGGGCACAAGCCUC 7652 AGCUGUGGGcAcAAGCCUCdTsdT antis
    1382-1401 7653 GGCUUGUGCCCACAGCUUC 7654 GGcuuGuGcccAcAGcuucdTsdT sense
    1382-1401 7655 GAAGCUGUGGGCACAAGCC 7656 GAAGCUGUGGGcAcAAGCCdTsdT antis
    1383-1402 7657 GCUUGUGCCCACAGCUUCU 7658 GcuuGuGcccAcAGcuucudTsdT sense
    1383-1402 7659 AGAAGCUGUGGGCACAAGC 7660 AGAAGCUGUGGGcAcAAGCdTsdT antis
    1384-1403 7661 CUUGUGCCCACAGCUUCUU 7662 cuuGuGcccAcAGcuucuudTsdT sense
    1384-1403 7663 AAGAAGCUGUGGGCACAAG 7664 AAGAAGCUGUGGGcAcAAGdTsdT antis
    1386-1405 7665 UGUGCCCACAGCUUCUUCG 7666 uGuGcccAcAGcuucuucGdTsdT sense
    1386-1405 7667 CGAAGAAGCUGUGGGCACA 7668 CGAAGAAGCUGUGGGcAcAdTsdT antis
    1424-1443 7669 AGCCCAGCUCCCCAACGAC 7670 AGcccAGcuccccAAcGAcdTsdT sense
    1424-1443 7671 GUCGUUGGGGAGCUGGGCU 7672 GUCGUUGGGGAGCUGGGCUdTsdT antis
    1425-1444 7673 GCCCAGCUCCCCAACGACC 7674 GcccAGcuccccAAcGAccdTsdT sense
    1425-1444 7675 GGUCGUUGGGGAGCUGGGC 7676 GGUCGUUGGGGAGCUGGGCdTsdT antis
    1426-1445 7677 CCCAGCUCCCCAACGACCG 7678 cccAGcuccccAAcGAccGdTsdT sense
    1426-1445 7679 CGGUCGUUGGGGAGCUGGG 7680 CGGUCGUUGGGGAGCUGGGdTsdT antis
    1427-1446 7681 CCAGCUCCCCAACGACCGC 7682 ccAGcuccccAAcGAccGcdTsdT sense
    1427-1446 7683 GCGGUCGUUGGGGAGCUGG 7684 GCGGUCGUUGGGGAGCUGGdTsdT antis
    1428-1447 7685 CAGCUCCCCAACGACCGCC 7686 cAGcuccccAAcGAccGccdTsdT sense
    1428-1447 7687 GGCGGUCGUUGGGGAGCUG 7688 GGCGGUCGUUGGGGAGCUGdTsdT antis
    1454-1473 7689 CCCCCUGUUCAACUUCAGU 7690 cccccuGuucAAcuucAGudTsdT sense
    1454-1473 7691 ACUGAAGUUGAACAGGGGG 7692 ACUGAAGUUGAAcAGGGGGdTsdT antis
    1459-1478 7693 UGUUCAACUUCAGUCCUGG 7694 uGuucAAcuucAGuccuGGdTsdT sense
    1459-1478 7695 CCAGGACUGAAGUUGAACA 7696 CcAGGACUGAAGUUGAAcAdTsdT antis
    1460-1479 7697 GUUCAACUUCAGUCCUGGU 7698 GuucAAcuucAGuccuGGudTsdT sense
    1460-1479 7699 ACCAGGACUGAAGUUGAAC 7700 ACcAGGACUGAAGUUGAACdTsdT antis
    1461-1480 7701 UUCAACUUCAGUCCUGGUG 7702 uucAAcuucAGuccuGGuGdTsdT sense
    1461-1480 7703 CACCAGGACUGAAGUUGAA 7704 cACcAGGACUGAAGUUGAAdTsdT antis
    1462-1481 7705 UCAACUUCAGUCCUGGUGA 7706 ucAAcuucAGuccuGGuGAdTsdT sense
    1462-1481 7707 UCACCAGGACUGAAGUUGA 7708 UcACcAGGACUGAAGUUGAdTsdT antis
    1463-1482 7709 CAACUUCAGUCCUGGUGAA 7710 cAAcuucAGuccuGGuGAAdTsdT sense
    1463-1482 7711 UUCACCAGGACUGAAGUUG 7712 UUcACcAGGACUGAAGUUGdTsdT antis
    1503-1522 7713 AAUGCCAUUCUCAUCCCUC 7714 AAuGccAuucucAucccucdTsdT sense
    1503-1522 7715 GAGGGAUGAGAAUGGCAUU 7716 GAGGGAUGAGAAUGGcAUUdTsdT antis
    1504-1523 7717 AUGCCAUUCUCAUCCCUCC 7718 AuGccAuucucAucccuccdTsdT sense
    1504-1523 7719 GGAGGGAUGAGAAUGGCAU 7720 GGAGGGAUGAGAAUGGcAUdTsdT antis
    1505-1524 7721 UGCCAUUCUCAUCCCUCCU 7722 uGccAuucucAucccuccudTsdT sense
    1505-1524 7723 AGGAGGGAUGAGAAUGGCA 7724 AGGAGGGAUGAGAAUGGcAdTsdT antis
    1506-1525 7725 GCCAUUCUCAUCCCUCCUC 7726 GccAuucucAucccuccucdTsdT sense
    1506-1525 7727 GAGGAGGGAUGAGAAUGGC 7728 GAGGAGGGAUGAGAAUGGCdTsdT antis
    1507-1526 7729 CCAUUCUCAUCCCUCCUCA 7730 ccAuucucAucccuccucAdTsdT sense
    1507-1526 7731 UGAGGAGGGAUGAGAAUGG 7732 UGAGGAGGGAUGAGAAUGGdTsdT antis
    1508-1527 7733 CAUUCUCAUCCCUCCUCAC 7734 cAuucucAucccuccucAcdTsdT sense
    1508-1527 7735 GUGAGGAGGGAUGAGAAUG 7736 GUGAGGAGGGAUGAGAAUGdTsdT antis
    1509-1528 7737 AUUCUCAUCCCUCCUCACU 7738 AuucucAucccuccucAcudTsdT sense
    1509-1528 7739 AGUGAGGAGGGAUGAGAAU 7740 AGUGAGGAGGGAUGAGAAUdTsdT antis
    1510-1529 7741 UUCUCAUCCCUCCUCACUU 7742 uucucAucccuccucAcuudTsdT sense
    1510-1529 7743 AAGUGAGGAGGGAUGAGAA 7744 AAGUGAGGAGGGAUGAGAAdTsdT antis
    1511-1530 7745 UCUCAUCCCUCCUCACUUG 7746 ucucAucccuccucAcuuGdTsdT sense
    1511-1530 7747 CAAGUGAGGAGGGAUGAGA 7748 cAAGUGAGGAGGGAUGAGAdTsdT antis
    1515-1534 7749 AUCCCUCCUCACUUGAGGU 7750 AucccuccucAcuuGAGGudTsdT sense
    1515-1534 7751 ACCUCAAGUGAGGAGGGAU 7752 ACCUcAAGUGAGGAGGGAUdTsdT antis
    1516-1535 7753 UCCCUCCUCACUUGAGGUC 7754 ucccuccucAcuuGAGGucdTsdT sense
    1516-1535 7755 GACCUCAAGUGAGGAGGGA 7756 GACCUcAAGUGAGGAGGGAdTsdT antis
    1520-1539 7757 UCCUCACUUGAGGUCCCCA 7758 uccucAcuuGAGGuccccAdTsdT sense
    1520-1539 7759 UGGGGACCUCAAGUGAGGA 7760 UGGGGACCUcAAGUGAGGAdTsdT antis
    1522-1541 7761 CUCACUUGAGGUCCCCAGC 7762 cucAcuuGAGGuccccAGcdTsdT sense
    1522-1541 7763 GCUGGGGACCUCAAGUGAG 7764 GCUGGGGACCUcAAGUGAGdTsdT antis
    1523-1542 7765 UCACUUGAGGUCCCCAGCA 7766 ucAcuuGAGGuccccAGcAdTsdT sense
    1523-1542 7767 UGCUGGGGACCUCAAGUGA 7768 UGCUGGGGACCUcAAGUGAdTsdT antis
    1524-1543 7769 CACUUGAGGUCCCCAGCAG 7770 cAcuuGAGGuccccAGcAGdTsdT sense
    1524-1543 7771 CUGCUGGGGACCUCAAGUG 7772 CUGCUGGGGACCUcAAGUGdTsdT antis
    1528-1547 7773 UGAGGUCCCCAGCAGGCCC 7774 uGAGGuccccAGcAGGcccdTsdT sense
    1528-1547 7775 GGGCCUGCUGGGGACCUCA 7776 GGGCCUGCUGGGGACCUcAdTsdT antis
    1529-1548 7777 GAGGUCCCCAGCAGGCCCU 7778 GAGGuccccAGcAGGcccudTsdT sense
    1529-1548 7779 AGGGCCUGCUGGGGACCUC 7780 AGGGCCUGCUGGGGACCUCdTsdT antis
    1539-1558 7781 GCAGGCCCUGCUUCUCCCC 7782 GcAGGcccuGcuucuccccdTsdT sense
    1539-1558 7783 GGGGAGAAGCAGGGCCUGC 7784 GGGGAGAAGcAGGGCCUGCdTsdT antis
    1577-1596 7785 AUCCUCACAAGCUUUAACU 7786 AuccucAcAAGcuuuAAcudTsdT sense
    1577-1596 7787 AGUUAAAGCUUGUGAGGAU 7788 AGUuAAAGCUUGUGAGGAUdTsdT antis
    1578-1597 7789 UCCUCACAAGCUUUAACUG 7790 uccucAcAAGcuuuAAcuGdTsdT sense
    1578-1597 7791 CAGUUAAAGCUUGUGAGGA 7792 cAGUuAAAGCUUGUGAGGAdTsdT antis
    1579-1598 7793 CCUCACAAGCUUUAACUGA 7794 ccucAcAAGcuuuAAcuGAdTsdT sense
    1579-1598 7795 UCAGUUAAAGCUUGUGAGG 7796 UcAGUuAAAGCUUGUGAGGdTsdT antis
    1582-1601 7797 CACAAGCUUUAACUGAAGC 7798 cAcAAGcuuuAAcuGAAGcdTsdT sense
    1582-1601 7799 GCUUCAGUUAAAGCUUGUG 7800 GCUUcAGUuAAAGCUUGUGdTsdT antis
    1587-1606 7801 GCUUUAACUGAAGCUCAGA 7802 GcuuuAAcuGAAGcucAGAdTsdT sense
    1587-1606 7803 UCUGAGCUUCAGUUAAAGC 7804 UCUGAGCUUcAGUuAAAGCdTsdT antis
    1623-1642 7805 CCAUCUGAUGCCACAACUG 7806 ccAucuGAuGccAcAAcuGdTsdT sense
    1623-1642 7807 CAGUUGUGGCAUCAGAUGG 7808 cAGUUGUGGcAUcAGAUGGdTsdT antis
    1624-1643 7809 CAUCUGAUGCCACAACUGC 7810 cAucuGAuGccAcAAcuGcdTsdT sense
    1624-1643 7811 GCAGUUGUGGCAUCAGAUG 7812 GcAGUUGUGGcAUcAGAUGdTsdT antis
    1625-1644 7813 AUCUGAUGCCACAACUGCU 7814 AucuGAuGccAcAAcuGcudTsdT sense
    1625-1644 7815 AGCAGUUGUGGCAUCAGAU 7816 AGcAGUUGUGGcAUcAGAUdTsdT antis
    1630-1649 7817 AUGCCACAACUGCUACCCU 7818 AuGccAcAAcuGcuAcccudTsdT sense
    1630-1649 7819 AGGGUAGCAGUUGUGGCAU 7820 AGGGuAGcAGUUGUGGcAUdTsdT antis
    1631-1650 7821 UGCCACAACUGCUACCCUC 7822 uGccAcAAcuGcuAcccucdTsdT sense
    1631-1650 7823 GAGGGUAGCAGUUGUGGCA 7824 GAGGGuAGcAGUUGUGGcAdTsdT antis
    1632-1651 7825 GCCACAACUGCUACCCUCG 7826 GccAcAAcuGcuAcccucGdTsdT sense
    1632-1651 7827 CGAGGGUAGCAGUUGUGGC 7828 CGAGGGuAGcAGUUGUGGCdTsdT antis
    1633-1652 7829 CCACAACUGCUACCCUCGC 7830 ccAcAAcuGcuAcccucGcdTsdT sense
    1633-1652 7831 GCGAGGGUAGCAGUUGUGG 7832 GCGAGGGuAGcAGUUGUGGdTsdT antis
    1668-1687 7833 CCCCACCGACUACCCCUCC 7834 ccccAccGAcuAccccuccdTsdT sense
    1668-1687 7835 GGAGGGGUAGUCGGUGGGG 7836 GGAGGGGuAGUCGGUGGGGdTsdT antis
    1678-1697 7837 UACCCCUCCACGUCCAUCU 7838 uAccccuccAcGuccAucudTsdT sense
    1678-1697 7839 AGAUGGACGUGGAGGGGUA 7840 AGAUGGACGUGGAGGGGuAdTsdT antis
    1681-1700 7841 CCCUCCACGUCCAUCUGGG 7842 cccuccAcGuccAucuGGGdTsdT sense
    1681-1700 7843 CCCAGAUGGACGUGGAGGG 7844 CCcAGAUGGACGUGGAGGGdTsdT antis
    1683-1702 7845 CUCCACGUCCAUCUGGGAA 7846 cuccAcGuccAucuGGGAAdTsdT sense
    1683-1702 7847 UUCCCAGAUGGACGUGGAG 7848 UUCCcAGAUGGACGUGGAGdTsdT antis
    1690-1709 7849 UCCAUCUGGGAAGGCCCAA 7850 uccAucuGGGAAGGcccAAdTsdT sense
    1690-1709 7851 UUGGGCCUUCCCAGAUGGA 7852 UUGGGCCUUCCcAGAUGGAdTsdT antis
    1691-1710 7853 CCAUCUGGGAAGGCCCAAG 7854 ccAucuGGGAAGGcccAAGdTsdT sense
    1691-1710 7855 CUUGGGCCUUCCCAGAUGG 7856 CUUGGGCCUUCCcAGAUGGdTsdT antis
    1692-1711 7857 CAUCUGGGAAGGCCCAAGU 7858 cAucuGGGAAGGcccAAGudTsdT sense
    1692-1711 7859 ACUUGGGCCUUCCCAGAUG 7860 ACUUGGGCCUUCCcAGAUGdTsdT antis
    1693-1712 7861 AUCUGGGAAGGCCCAAGUG 7862 AucuGGGAAGGcccAAGuGdTsdT sense
    1693-1712 7863 CACUUGGGCCUUCCCAGAU 7864 cACUUGGGCCUUCCcAGAUdTsdT antis
    1696-1715 7865 UGGGAAGGCCCAAGUGGCG 7866 uGGGAAGGcccAAGuGGcGdTsdT sense
    1696-1715 7867 CGCCACUUGGGCCUUCCCA 7868 CGCcACUUGGGCCUUCCcAdTsdT antis
    1697-1716 7869 GGGAAGGCCCAAGUGGCGC 7870 GGGAAGGcccAAGuGGcGcdTsdT sense
    1697-1716 7871 GCGCCACUUGGGCCUUCCC 7872 GCGCcACUUGGGCCUUCCCdTsdT antis
    1698-1717 7873 GGAAGGCCCAAGUGGCGCU 7874 GGAAGGcccAAGuGGcGcudTsdT sense
    1698-1717 7875 AGCGCCACUUGGGCCUUCC 7876 AGCGCcACUUGGGCCUUCCdTsdT antis
    1699-1718 7877 GAAGGCCCAAGUGGCGCUG 7878 GAAGGcccAAGuGGcGcuGdTsdT sense
    1699-1718 7879 CAGCGCCACUUGGGCCUUC 7880 cAGCGCcACUUGGGCCUUCdTsdT antis
    1700-1719 7881 AAGGCCCAAGUGGCGCUGG 7882 AAGGcccAAGuGGcGcuGGdTsdT sense
    1700-1719 7883 CCAGCGCCACUUGGGCCUU 7884 CcAGCGCcACUUGGGCCUUdTsdT antis
    1701-1720 7885 AGGCCCAAGUGGCGCUGGG 7886 AGGcccAAGuGGcGcuGGGdTsdT sense
    1701-1720 7887 CCCAGCGCCACUUGGGCCU 7888 CCcAGCGCcACUUGGGCCUdTsdT antis
    1702-1721 7889 GGCCCAAGUGGCGCUGGGA 7890 GGcccAAGuGGcGcuGGGAdTsdT sense
    1702-1721 7891 UCCCAGCGCCACUUGGGCC 7892 UCCcAGCGCcACUUGGGCCdTsdT antis
    1707-1726 7893 AAGUGGCGCUGGGAAGGGG 7894 AAGuGGcGcuGGGAAGGGGdTsdT sense
    1707-1726 7895 CCCCUUCCCAGCGCCACUU 7896 CCCCUUCCcAGCGCcACUUdTsdT antis
    1708-1727 7897 AGUGGCGCUGGGAAGGGGG 7898 AGuGGcGcuGGGAAGGGGGdTsdT sense
    1708-1727 7899 CCCCCUUCCCAGCGCCACU 7900 CCCCCUUCCcAGCGCcACUdTsdT antis
    1712-1731 7901 GCGCUGGGAAGGGGGCCAC 7902 GcGcuGGGAAGGGGGccAcdTsdT sense
    1712-1731 7903 GUGGCCCCCUUCCCAGCGC 7904 GUGGCCCCCUUCCcAGCGCdTsdT antis
    1713-1732 7905 CGCUGGGAAGGGGGCCACA 7906 cGcuGGGAAGGGGGccAcAdTsdT sense
    1713-1732 7907 UGUGGCCCCCUUCCCAGCG 7908 UGUGGCCCCCUUCCcAGCGdTsdT antis
    1715-1734 7909 CUGGGAAGGGGGCCACAGC 7910 cuGGGAAGGGGGccAcAGcdTsdT sense
    1715-1734 7911 GCUGUGGCCCCCUUCCCAG 7912 GCUGUGGCCCCCUUCCcAGdTsdT antis
    1716-1735 7913 UGGGAAGGGGGCCACAGCC 7914 uGGGAAGGGGGccAcAGccdTsdT sense
    1716-1735 7915 GGCUGUGGCCCCCUUCCCA 7916 GGCUGUGGCCCCCUUCCcAdTsdT antis
    1717-1736 7917 GGGAAGGGGGCCACAGCCC 7918 GGGAAGGGGGccAcAGcccdTsdT sense
    1717-1736 7919 GGGCUGUGGCCCCCUUCCC 7920 GGGCUGUGGCCCCCUUCCCdTsdT antis
    1718-1737 7921 GGAAGGGGGCCACAGCCCA 7922 GGAAGGGGGccAcAGcccAdTsdT sense
    1718-1737 7923 UGGGCUGUGGCCCCCUUCC 7924 UGGGCUGUGGCCCCCUUCCdTsdT antis
    1719-1738 7925 GAAGGGGGCCACAGCCCAU 7926 GAAGGGGGccAcAGcccAudTsdT sense
    1719-1738 7927 AUGGGCUGUGGCCCCCUUC 7928 AUGGGCUGUGGCCCCCUUCdTsdT antis
    1720-1739 7929 AAGGGGGCCACAGCCCAUC 7930 AAGGGGGccAcAGcccAucdTsdT sense
    1720-1739 7931 GAUGGGCUGUGGCCCCCUU 7932 GAUGGGCUGUGGCCCCCUUdTsdT antis
    1721-1740 7933 AGGGGGCCACAGCCCAUCA 7934 AGGGGGccAcAGcccAucAdTsdT sense
    1721-1740 7935 UGAUGGGCUGUGGCCCCCU 7936 UGAUGGGCUGUGGCCCCCUdTsdT antis
    1724-1743 7937 GGGCCACAGCCCAUCAAGC 7938 GGGccAcAGcccAucAAGcdTsdT sense
    1724-1743 7939 GCUUGAUGGGCUGUGGCCC 7940 GCUUGAUGGGCUGUGGCCCdTsdT antis
    1725-1744 7941 GGCCACAGCCCAUCAAGCU 7942 GGccAcAGcccAucAAGcudTsdT sense
    1725-1744 7943 AGCUUGAUGGGCUGUGGCC 7944 AGCUUGAUGGGCUGUGGCCdTsdT antis
    1727-1746 7945 CCACAGCCCAUCAAGCUCC 7946 ccAcAGcccAucAAGcuccdTsdT sense
    1727-1746 7947 GGAGCUUGAUGGGCUGUGG 7948 GGAGCUUGAUGGGCUGUGGdTsdT antis
    1728-1747 7949 CACAGCCCAUCAAGCUCCU 7950 cAcAGcccAucAAGcuccudTsdT sense
    1728-1747 7951 AGGAGCUUGAUGGGCUGUG 7952 AGGAGCUUGAUGGGCUGUGdTsdT antis
    1729-1748 7953 ACAGCCCAUCAAGCUCCUG 7954 AcAGcccAucAAGcuccuGdTsdT sense
    1729-1748 7955 CAGGAGCUUGAUGGGCUGU 7956 cAGGAGCUUGAUGGGCUGUdTsdT antis
    1733-1752 7957 CCCAUCAAGCUCCUGCCCU 7958 cccAucAAGcuccuGcccudTsdT sense
    1733-1752 7959 AGGGCAGGAGCUUGAUGGG 7960 AGGGcAGGAGCUUGAUGGGdTsdT antis
    1734-1753 7961 CCAUCAAGCUCCUGCCCUG 7962 ccAucAAGcuccuGcccuGdTsdT sense
    1734-1753 7963 CAGGGCAGGAGCUUGAUGG 7964 cAGGGcAGGAGCUUGAUGGdTsdT antis
    1735-1754 7965 CAUCAAGCUCCUGCCCUGG 7966 cAucAAGcuccuGcccuGGdTsdT sense
    1735-1754 7967 CCAGGGCAGGAGCUUGAUG 7968 CcAGGGcAGGAGCUUGAUGdTsdT antis
    1736-1755 7969 AUCAAGCUCCUGCCCUGGC 7970 AucAAGcuccuGcccuGGcdTsdT sense
    1736-1755 7971 GCCAGGGCAGGAGCUUGAU 7972 GCcAGGGcAGGAGCUUGAUdTsdT antis
    1738-1757 7973 CAAGCUCCUGCCCUGGCUG 7974 cAAGcuccuGcccuGGcuGdTsdT sense
    1738-1757 7975 CAGCCAGGGCAGGAGCUUG 7976 cAGCcAGGGcAGGAGCUUGdTsdT antis
    1739-1758 7977 AAGCUCCUGCCCUGGCUGG 7978 AAGcuccuGcccuGGcuGGdTsdT sense
    1739-1758 7979 CCAGCCAGGGCAGGAGCUU 7980 CcAGCcAGGGcAGGAGCUUdTsdT antis
    1742-1761 7981 CUCCUGCCCUGGCUGGGCC 7982 cuccuGcccuGGcuGGGccdTsdT sense
    1742-1761 7983 GGCCCAGCCAGGGCAGGAG 7984 GGCCcAGCcAGGGcAGGAGdTsdT antis
    1745-1764 7985 CUGCCCUGGCUGGGCCCCU 7986 cuGcccuGGcuGGGccccudTsdT sense
    1745-1764 7987 AGGGGCCCAGCCAGGGCAG 7988 AGGGGCCcAGCcAGGGcAGdTsdT antis
    1747-1766 7989 GCCCUGGCUGGGCCCCUAG 7990 GcccuGGcuGGGccccuAGdTsdT sense
    1747-1766 7991 CUAGGGGCCCAGCCAGGGC 7992 CuAGGGGCCcAGCcAGGGCdTsdT antis
    1749-1768 7993 CCUGGCUGGGCCCCUAGAC 7994 ccuGGcuGGGccccuAGAcdTsdT sense
    1749-1768 7995 GUCUAGGGGCCCAGCCAGG 7996 GUCuAGGGGCCcAGCcAGGdTsdT antis
    1750-1769 7997 CUGGCUGGGCCCCUAGACU 7998 cuGGcuGGGccccuAGAcudTsdT sense
    1750-1769 7999 AGUCUAGGGGCCCAGCCAG 8000 AGUCuAGGGGCCcAGCcAGdTsdT antis
    1751-1770 8001 UGGCUGGGCCCCUAGACUA 8002 uGGcuGGGccccuAGAcuAdTsdT sense
    1751-1770 8003 UAGUCUAGGGGCCCAGCCA 8004 uAGUCuAGGGGCCcAGCcAdTsdT antis
    1754-1773 8005 CUGGGCCCCUAGACUAGAG 8006 cuGGGccccuAGAcuAGAGdTsdT sense
    1754-1773 8007 CUCUAGUCUAGGGGCCCAG 8008 CUCuAGUCuAGGGGCCcAGdTsdT antis
    1756-1775 8009 GGGCCCCUAGACUAGAGGG 8010 GGGccccuAGAcuAGAGGGdTsdT sense
    1756-1775 8011 CCCUCUAGUCUAGGGGCCC 8012 CCCUCuAGUCuAGGGGCCCdTsdT antis
    1757-1776 8013 GGCCCCUAGACUAGAGGGC 8014 GGccccuAGAcuAGAGGGcdTsdT sense
    1757-1776 8015 GCCCUCUAGUCUAGGGGCC 8016 GCCCUCuAGUCuAGGGGCCdTsdT antis
    1762-1781 8017 CUAGACUAGAGGGCAGAGG 8018 cuAGAcuAGAGGGcAGAGGdTsdT sense
    1762-1781 8019 CCUCUGCCCUCUAGUCUAG 8020 CCUCUGCCCUCuAGUCuAGdTsdT antis
    1766-1785 8021 ACUAGAGGGCAGAGGUAAA 8022 AcuAGAGGGcAGAGGuAAAdTsdT sense
    1766-1785 8023 UUUACCUCUGCCCUCUAGU 8024 UUuACCUCUGCCCUCuAGUdTsdT antis
    1768-1787 8025 UAGAGGGCAGAGGUAAAUG 8026 uAGAGGGcAGAGGuAAAuGdTsdT sense
    1768-1787 8027 CAUUUACCUCUGCCCUCUA 8028 cAUUuACCUCUGCCCUCuAdTsdT antis
    1771-1790 8029 AGGGCAGAGGUAAAUGAAC 8030 AGGGcAGAGGuAAAuGAAcdTsdT sense
    1771-1790 8031 GUUCAUUUACCUCUGCCCU 8032 GUUcAUUuACCUCUGCCCUdTsdT antis
    1776-1795 8033 AGAGGUAAAUGAACUACCC 8034 AGAGGuAAAuGAAcuAcccdTsdT sense
    1776-1795 8035 GGGUAGUUCAUUUACCUCU 8036 GGGuAGUUcAUUuACCUCUdTsdT antis
    1783-1802 8037 AAUGAACUACCCCCAGCAU 8038 AAuGAAcuAcccccAGcAudTsdT sense
    1783-1802 8039 AUGCUGGGGGUAGUUCAUU 8040 AUGCUGGGGGuAGUUcAUUdTsdT antis
    1788-1807 8041 ACUACCCCCAGCAUCUAGG 8042 AcuAcccccAGcAucuAGGdTsdT sense
    1788-1807 8043 CCUAGAUGCUGGGGGUAGU 8044 CCuAGAUGCUGGGGGuAGUdTsdT antis
    1789-1808 8045 CUACCCCCAGCAUCUAGGC 8046 cuAcccccAGcAucuAGGcdTsdT sense
    1789-1808 8047 GCCUAGAUGCUGGGGGUAG 8048 GCCuAGAUGCUGGGGGuAGdTsdT antis
    1791-1810 8049 ACCCCCAGCAUCUAGGCCU 8050 AcccccAGcAucuAGGccudTsdT sense
    1791-1810 8051 AGGCCUAGAUGCUGGGGGU 8052 AGGCCuAGAUGCUGGGGGUdTsdT antis
    1793-1812 8053 CCCCAGCAUCUAGGCCUCC 8054 ccccAGcAucuAGGccuccdTsdT sense
    1793-1812 8055 GGAGGCCUAGAUGCUGGGG 8056 GGAGGCCuAGAUGCUGGGGdTsdT antis
    1797-1816 8057 AGCAUCUAGGCCUCCCUCA 8058 AGcAucuAGGccucccucAdTsdT sense
    1797-1816 8059 UGAGGGAGGCCUAGAUGCU 8060 UGAGGGAGGCCuAGAUGCUdTsdT antis
    1822-1841 8061 UAACCUCUGUGGUGGGCUU 8062 uAAccucuGuGGuGGGcuudTsdT sense
    1822-1841 8063 AAGCCCACCACAGAGGUUA 8064 AAGCCcACcAcAGAGGUuAdTsdT antis
    1823-1842 8065 AACCUCUGUGGUGGGCUUU 8066 AAccucuGuGGuGGGcuuudTsdT sense
    1823-1842 8067 AAAGCCCACCACAGAGGUU 8068 AAAGCCcACcAcAGAGGUUdTsdT antis
    1826-1845 8069 CUCUGUGGUGGGCUUUUUA 8070 cucuGuGGuGGGcuuuuuAdTsdT sense
    1826-1845 8071 UAAAAAGCCCACCACAGAG 8072 uAAAAAGCCcACcAcAGAGdTsdT antis
    1827-1846 8073 UCUGUGGUGGGCUUUUUAA 8074 ucuGuGGuGGGcuuuuuAAdTsdT sense
    1827-1846 8075 UUAAAAAGCCCACCACAGA 8076 UuAAAAAGCCcACcAcAGAdTsdT antis
    1828-1847 8077 CUGUGGUGGGCUUUUUAAA 8078 cuGuGGuGGGcuuuuuAAAdTsdT sense
    1828-1847 8079 UUUAAAAAGCCCACCACAG 8080 UUuAAAAAGCCcACcAcAGdTsdT antis
    1829-1848 8081 UGUGGUGGGCUUUUUAAAG 8082 uGuGGuGGGcuuuuuAAAGdTsdT sense
    1829-1848 8083 CUUUAAAAAGCCCACCACA 8084 CUUuAAAAAGCCcACcAcAdTsdT antis
    1830-1849 8085 GUGGUGGGCUUUUUAAAGA 8086 GuGGuGGGcuuuuuAAAGAdTsdT sense
    1830-1849 8087 UCUUUAAAAAGCCCACCAC 8088 UCUUuAAAAAGCCcACcACdTsdT antis
    1832-1851 8089 GGUGGGCUUUUUAAAGAGG 8090 GGuGGGcuuuuuAAAGAGGdTsdT sense
    1832-1851 8091 CCUCUUUAAAAAGCCCACC 8092 CCUCUUuAAAAAGCCcACCdTsdT antis
    1835-1854 8093 GGGCUUUUUAAAGAGGAUU 8094 GGGcuuuuuAAAGAGGAuudTsdT sense
    1835-1854 8095 AAUCCUCUUUAAAAAGCCC 8096 AAUCCUCUUuAAAAAGCCCdTsdT antis
    1836-1855 8097 GGCUUUUUAAAGAGGAUUU 8098 GGcuuuuuAAAGAGGAuuudTsdT sense
    1836-1855 8099 AAAUCCUCUUUAAAAAGCC 8100 AAAUCCUCUUuAAAAAGCCdTsdT antis
    1884-1903 8101 AAGGACGGGGUUUGGGGGU 8102 AAGGAcGGGGuuuGGGGGudTsdT sense
    1884-1903 8103 ACCCCCAAACCCCGUCCUU 8104 ACCCCcAAACCCCGUCCUUdTsdT antis
    1886-1905 8105 GGACGGGGUUUGGGGGUGU 8106 GGAcGGGGuuuGGGGGuGudTsdT sense
    1886-1905 8107 ACACCCCCAAACCCCGUCC 8108 AcACCCCcAAACCCCGUCCdTsdT antis
    1889-1908 8109 CGGGGUUUGGGGGUGUGAG 8110 cGGGGuuuGGGGGuGuGAGdTsdT sense
    1889-1908 8111 CUCACACCCCCAAACCCCG 8112 CUcAcACCCCcAAACCCCGdTsdT antis
    1890-1909 8113 GGGGUUUGGGGGUGUGAGG 8114 GGGGuuuGGGGGuGuGAGGdTsdT sense
    1890-1909 8115 CCUCACACCCCCAAACCCC 8116 CCUcAcACCCCcAAACCCCdTsdT antis
    1891-1910 8117 GGGUUUGGGGGUGUGAGGA 8118 GGGuuuGGGGGuGuGAGGAdTsdT sense
    1891-1910 8119 UCCUCACACCCCCAAACCC 8120 UCCUcAcACCCCcAAACCCdTsdT antis
    1892-1911 8121 GGUUUGGGGGUGUGAGGAC 8122 GGuuuGGGGGuGuGAGGAcdTsdT sense
    1892-1911 8123 GUCCUCACACCCCCAAACC 8124 GUCCUcAcACCCCcAAACCdTsdT antis
    1893-1912 8125 GUUUGGGGGUGUGAGGACC 8126 GuuuGGGGGuGuGAGGAccdTsdT sense
    1893-1912 8127 GGUCCUCACACCCCCAAAC 8128 GGUCCUcAcACCCCcAAACdTsdT antis
    1894-1913 8129 UUUGGGGGUGUGAGGACCU 8130 uuuGGGGGuGuGAGGAccudTsdT sense
    1894-1913 8131 AGGUCCUCACACCCCCAAA 8132 AGGUCCUcAcACCCCcAAAdTsdT antis
    1895-1914 8133 UUGGGGGUGUGAGGACCUU 8134 uuGGGGGuGuGAGGAccuudTsdT sense
    1895-1914 8135 AAGGUCCUCACACCCCCAA 8136 AAGGUCCUcAcACCCCcAAdTsdT antis
    1914-1933 8137 CUACCCCCUUGGUCCCCUC 8138 cuAcccccuuGGuccccucdTsdT sense
    1914-1933 8139 GAGGGGACCAAGGGGGUAG 8140 GAGGGGACcAAGGGGGuAGdTsdT antis
    1915-1934 8141 UACCCCCUUGGUCCCCUCC 8142 uAcccccuuGGuccccuccdTsdT sense
    1915-1934 8143 GGAGGGGACCAAGGGGGUA 8144 GGAGGGGACcAAGGGGGuAdTsdT antis
    1916-1935 8145 ACCCCCUUGGUCCCCUCCC 8146 AcccccuuGGuccccucccdTsdT sense
    1916-1935 8147 GGGAGGGGACCAAGGGGGU 8148 GGGAGGGGACcAAGGGGGUdTsdT antis
    1917-1936 8149 CCCCCUUGGUCCCCUCCCC 8150 cccccuuGGuccccuccccdTsdT sense
    1917-1936 8151 GGGGAGGGGACCAAGGGGG 8152 GGGGAGGGGACcAAGGGGGdTsdT antis
    1918-1937 8153 CCCCUUGGUCCCCUCCCCU 8154 ccccuuGGuccccuccccudTsdT sense
    1918-1937 8155 AGGGGAGGGGACCAAGGGG 8156 AGGGGAGGGGACcAAGGGGdTsdT antis
    1919-1938 8157 CCCUUGGUCCCCUCCCCUC 8158 cccuuGGuccccuccccucdTsdT sense
    1919-1938 8159 GAGGGGAGGGGACCAAGGG 8160 GAGGGGAGGGGACcAAGGGdTsdT antis
    1920-1939 8161 CCUUGGUCCCCUCCCCUCC 8162 ccuuGGuccccuccccuccdTsdT sense
    1920-1939 8163 GGAGGGGAGGGGACCAAGG 8164 GGAGGGGAGGGGACcAAGGdTsdT antis
    1921-1940 8165 CUUGGUCCCCUCCCCUCCC 8166 cuuGGuccccuccccucccdTsdT sense
    1921-1940 8167 GGGAGGGGAGGGGACCAAG 8168 GGGAGGGGAGGGGACcAAGdTsdT antis
    1922-1941 8169 UUGGUCCCCUCCCCUCCCC 8170 uuGGuccccuccccuccccdTsdT sense
    1922-1941 8171 GGGGAGGGGAGGGGACCAA 8172 GGGGAGGGGAGGGGACcAAdTsdT antis
    2116-2135 8173 UUCUUGUCCUCUGCUCCCA 8174 uucuuGuccucuGcucccAdTsdT sense
    2116-2135 8175 UGGGAGCAGAGGACAAGAA 8176 UGGGAGcAGAGGAcAAGAAdTsdT antis
    213-232 8177 GGAGGCGGCCCUGGGGGCU 8178 GGAGGcGGcccuGGGGGcudTsdT sense
    213-232 8179 AGCCCCCAGGGCCGCCUCC 8180 AGCCCCcAGGGCCGCCUCCdTsdT antis
    358-377 8181 UGGGUGGGGGCGUGGGAGC 8182 uGGGuGGGGGcGuGGGAGcdTsdT sense
    358-377 8183 GCUCCCACGCCCCCACCCA 8184 GCUCCcACGCCCCcACCcAdTsdT antis
    528-547 8185 CGUUCCCAAGAAGUGGCUU 8186 cGuucccAAGAAGuGGcuudTsdT sense
    528-547 8187 AAGCCACUUCUUGGGAACG 8188 AAGCcACUUCUUGGGAACGdTsdT antis
    559-578 8189 AAGUGAUUGGUAAUGGCUC 8190 AAGuGAuuGGuAAuGGcucdTsdT sense
    559-578 8191 GAGCCAUUACCAAUCACUU 8192 GAGCcAUuACcAAUcACUUdTsdT antis
    623-642 8193 GGUGGCCAUCAAGAAGGUU 8194 GGuGGccAucAAGAAGGuudTsdT sense
    623-642 8195 AACCUUCUUGAUGGCCACC 8196 AACCUUCUUGAUGGCcACCdTsdT antis
    630-649 8197 AUCAAGAAGGUUCUUCAGG 8198 AucAAGAAGGuucuucAGGdTsdT sense
    630-649 8199 CCUGAAGAACCUUCUUGAU 8200 CCUGAAGAACCUUCUUGAUdTsdT antis
    633-652 8201 AAGAAGGUUCUUCAGGACA 8202 AAGAAGGuucuucAGGAcAdTsdT sense
    633-652 8203 UGUCCUGAAGAACCUUCUU 8204 UGUCCUGAAGAACCUUCUUdTsdT antis
    801-820 8205 CGAGUGGCCCGCCACUUCA 8206 cGAGuGGcccGccAcuucAdTsdT sense
    801-820 8207 UGAAGUGGCGGGCCACUCG 8208 UGAAGUGGCGGGCcACUCGdTsdT antis
    859-878 8209 UGUACAUGUACCAGCUCUU 8210 uGuAcAuGuAccAGcucuudTsdT sense
    859-878 8211 AAGAGCUGGUACAUGUACA 8212 AAGAGCUGGuAcAUGuAcAdTsdT antis
    936-955 8213 AAUUUGCUUGUGGACCCUG 8214 AAuuuGcuuGuGGAcccuGdTsdT sense
    936-955 8215 CAGGGUCCACAAGCAAAUU 8216 cAGGGUCcAcAAGcAAAUUdTsdT antis
    944-963 8217 UGUGGACCCUGACACUGCU 8218 uGuGGAcccuGAcAcuGcudTsdT sense
    944-963 8219 AGCAGUGUCAGGGUCCACA 8220 AGcAGUGUcAGGGUCcAcAdTsdT antis
    960-979 8221 GCUGUCCUCAAGCUCUGCG 8222 GcuGuccucAAGcucuGcGdTsdT sense
    960-979 8223 CGCAGAGCUUGAGGACAGC 8224 CGcAGAGCUUGAGGAcAGCdTsdT antis
    966-985 8225 CUCAAGCUCUGCGAUUUUG 8226 cucAAGcucuGcGAuuuuGdTsdT sense
    966-985 8227 CAAAAUCGCAGAGCUUGAG 8228 cAAAAUCGcAGAGCUUGAGdTsdT antis
     982-1001 8229 UUGGCAGUGCAAAGCAGCU 8230 uuGGcAGuGcAAAGcAGcudTsdT sense
     982-1001 8231 AGCUGCUUUGCACUGCCAA 8232 AGCUGCUUUGcACUGCcAAdTsdT antis
     983-1002 8233 UGGCAGUGCAAAGCAGCUG 8234 uGGcAGuGcAAAGcAGcuGdTsdT sense
     983-1002 8235 CAGCUGCUUUGCACUGCCA 8236 cAGCUGCUUUGcACUGCcAdTsdT antis
    1170-1189 8237 GACCAGCUUGUGGAGAUCA 8238 GAccAGcuuGuGGAGAucAdTsdT sense
    1170-1189 8239 UGAUCUCCACAAGCUGGUC 8240 UGAUCUCcAcAAGCUGGUCdTsdT antis
    1210-1229 8241 CCAGGGAACAAAUCCGAGA 8242 ccAGGGAAcAAAuccGAGAdTsdT sense
    1210-1229 8243 UCUCGGAUUUGUUCCCUGG 8244 UCUCGGAUUUGUUCCCUGGdTsdT antis
    1521-1540 8245 CCUCACUUGAGGUCCCCAG 8246 ccucAcuuGAGGuccccAGdTsdT sense
    1521-1540 8247 CUGGGGACCUCAAGUGAGG 8248 CUGGGGACCUcAAGUGAGGdTsdT antis
    1533-1552 8249 UCCCCAGCAGGCCCUGCUU 8250 uccccAGcAGGcccuGcuudTsdT sense
    1533-1552 8251 AAGCAGGGCCUGCUGGGGA 8252 AAGcAGGGCCUGCUGGGGAdTsdT antis
    1534-1553 8253 CCCCAGCAGGCCCUGCUUC 8254 ccccAGcAGGcccuGcuucdTsdT sense
    1534-1553 8255 GAAGCAGGGCCUGCUGGGG 8256 GAAGcAGGGCCUGCUGGGGdTsdT antis
    1679-1698 8257 ACCCCUCCACGUCCAUCUG 8258 AccccuccAcGuccAucuGdTsdT sense
    1679-1698 8259 CAGAUGGACGUGGAGGGGU 8260 cAGAUGGACGUGGAGGGGUdTsdT antis
    1680-1699 8261 CCCCUCCACGUCCAUCUGG 8262 ccccuccAcGuccAucuGGdTsdT sense
    1680-1699 8263 CCAGAUGGACGUGGAGGGG 8264 CcAGAUGGACGUGGAGGGGdTsdT antis
    1684-1703 8265 UCCACGUCCAUCUGGGAAG 8266 uccAcGuccAucuGGGAAGdTsdT sense
    1684-1703 8267 CUUCCCAGAUGGACGUGGA 8268 CUUCCcAGAUGGACGUGGAdTsdT antis
    1710-1729 8269 UGGCGCUGGGAAGGGGGCC 8270 uGGcGcuGGGAAGGGGGccdTsdT sense
    1710-1729 8271 GGCCCCCUUCCCAGCGCCA 8272 GGCCCCCUUCCcAGCGCcAdTsdT antis
    1711-1730 8273 GGCGCUGGGAAGGGGGCCA 8274 GGcGcuGGGAAGGGGGccAdTsdT sense
    1711-1730 8275 UGGCCCCCUUCCCAGCGCC 8276 UGGCCCCCUUCCcAGCGCCdTsdT antis
    1726-1745 8277 GCCACAGCCCAUCAAGCUC 8278 GccAcAGcccAucAAGcucdTsdT sense
    1726-1745 8279 GAGCUUGAUGGGCUGUGGC 8280 GAGCUUGAUGGGCUGUGGCdTsdT antis
    1731-1750 8281 AGCCCAUCAAGCUCCUGCC 8282 AGcccAucAAGcuccuGccdTsdT sense
    1731-1750 8283 GGCAGGAGCUUGAUGGGCU 8284 GGcAGGAGCUUGAUGGGCUdTsdT antis
    1740-1759 8285 AGCUCCUGCCCUGGCUGGG 8286 AGcuccuGcccuGGcuGGGdTsdT sense
    1740-1759 8287 CCCAGCCAGGGCAGGAGCU 8288 CCcAGCcAGGGcAGGAGCUdTsdT antis
    1741-1760 8289 GCUCCUGCCCUGGCUGGGC 8290 GcuccuGcccuGGcuGGGcdTsdT sense
    1741-1760 8291 GCCCAGCCAGGGCAGGAGC 8292 GCCcAGCcAGGGcAGGAGCdTsdT antis
    1767-1786 8293 CUAGAGGGCAGAGGUAAAU 8294 cuAGAGGGcAGAGGuAAAudTsdT sense
    1767-1786 8295 AUUUACCUCUGCCCUCUAG 8296 AUUuACCUCUGCCCUCuAGdTsdT antis
    1772-1791 8297 GGGCAGAGGUAAAUGAACU 8298 GGGcAGAGGuAAAuGAAcudTsdT sense
    1772-1791 8299 AGUUCAUUUACCUCUGCCC 8300 AGUUcAUUuACCUCUGCCCdTsdT antis
    1775-1794 8301 CAGAGGUAAAUGAACUACC 8302 cAGAGGuAAAuGAAcuAccdTsdT sense
    1775-1794 8303 GGUAGUUCAUUUACCUCUG 8304 GGuAGUUcAUUuACCUCUGdTsdT antis
    1824-1843 8305 ACCUCUGUGGUGGGCUUUU 8306 AccucuGuGGuGGGcuuuudTsdT sense
    1824-1843 8307 AAAAGCCCACCACAGAGGU 8308 AAAAGCCcACcAcAGAGGUdTsdT antis
    1834-1853 8309 UGGGCUUUUUAAAGAGGAU 8310 uGGGcuuuuuAAAGAGGAudTsdT sense
    1834-1853 8311 AUCCUCUUUAAAAAGCCCA 8312 AUCCUCUUuAAAAAGCCcAdTsdT antis
    2015-2034 8313 UUCCCUUCCCUGGCCCCCU 8314 uucccuucccuGGcccccudTsdT sense
    2015-2034 8315 AGGGGGCCAGGGAAGGGAA 8316 AGGGGGCcAGGGAAGGGAAdTsdT antis
    69-88 8317 GGAGCCGGAGCCCGAACGG 8318 GGAGccGGAGcccGAAcGGdTsdT sense
    69-88 8319 CCGUUCGGGCUCCGGCUCC 8320 CCGUUCGGGCUCCGGCUCCdTsdT antis
    112-131 8321 CAGGGGAGGCGGCGGCAGA 8322 cAGGGGAGGcGGcGGcAGAdTsdT sense
    112-131 8323 UCUGCCGCCGCCUCCCCUG 8324 UCUGCCGCCGCCUCCCCUGdTsdT antis
    113-132 8325 AGGGGAGGCGGCGGCAGAG 8326 AGGGGAGGcGGcGGcAGAGdTsdT sense
    113-132 8327 CUCUGCCGCCGCCUCCCCU 8328 CUCUGCCGCCGCCUCCCCUdTsdT antis
    114-133 8329 GGGGAGGCGGCGGCAGAGG 8330 GGGGAGGcGGcGGcAGAGGdTsdT sense
    114-133 8331 CCUCUGCCGCCGCCUCCCC 8332 CCUCUGCCGCCGCCUCCCCdTsdT antis
    116-135 8333 GGAGGCGGCGGCAGAGGCA 8334 GGAGGcGGcGGcAGAGGcAdTsdT sense
    116-135 8335 UGCCUCUGCCGCCGCCUCC 8336 UGCCUCUGCCGCCGCCUCCdTsdT antis
    130-149 8337 AGGCAGCGGCGGGGGCAGC 8338 AGGcAGcGGcGGGGGcAGcdTsdT sense
    130-149 8339 GCUGCCCCCGCCGCUGCCU 8340 GCUGCCCCCGCCGCUGCCUdTsdT antis
    131-150 8341 GGCAGCGGCGGGGGCAGCC 8342 GGcAGcGGcGGGGGcAGccdTsdT sense
    131-150 8343 GGCUGCCCCCGCCGCUGCC 8344 GGCUGCCCCCGCCGCUGCCdTsdT antis
    166-185 8345 CGCGGCCUGGGCCUGCGCU 8346 cGcGGccuGGGccuGcGcudTsdT sense
    166-185 8347 AGCGCAGGCCCAGGCCGCG 8348 AGCGcAGGCCcAGGCCGCGdTsdT antis
    272-291 8349 CGGAGGCGGAGGUGGUGGC 8350 cGGAGGcGGAGGuGGuGGcdTsdT sense
    272-291 8351 GCCACCACCUCCGCCUCCG 8352 GCcACcACCUCCGCCUCCGdTsdT antis
    273-292 8353 GGAGGCGGAGGUGGUGGCG 8354 GGAGGcGGAGGuGGuGGcGdTsdT sense
    273-292 8355 CGCCACCACCUCCGCCUCC 8356 CGCcACcACCUCCGCCUCCdTsdT antis
    274-293 8357 GAGGCGGAGGUGGUGGCGG 8358 GAGGcGGAGGuGGuGGcGGdTsdT sense
    274-293 8359 CCGCCACCACCUCCGCCUC 8360 CCGCcACcACCUCCGCCUCdTsdT antis
    276-295 8361 GGCGGAGGUGGUGGCGGCG 8362 GGcGGAGGuGGuGGcGGcGdTsdT sense
    276-295 8363 CGCCGCCACCACCUCCGCC 8364 CGCCGCcACcACCUCCGCCdTsdT antis
    277-296 8365 GCGGAGGUGGUGGCGGCGG 8366 GcGGAGGuGGuGGcGGcGGdTsdT sense
    277-296 8367 CCGCCGCCACCACCUCCGC 8368 CCGCCGCcACcACCUCCGCdTsdT antis
    285-304 8369 GGUGGCGGCGGCCCCGGGG 8370 GGuGGcGGcGGccccGGGGdTsdT sense
    285-304 8371 CCCCGGGGCCGCCGCCACC 8372 CCCCGGGGCCGCCGCcACCdTsdT antis
    286-305 8373 GUGGCGGCGGCCCCGGGGG 8374 GuGGcGGcGGccccGGGGGdTsdT sense
    286-305 8375 CCCCCGGGGCCGCCGCCAC 8376 CCCCCGGGGCCGCCGCcACdTsdT antis
    287-306 8377 UGGCGGCGGCCCCGGGGGC 8378 uGGcGGcGGccccGGGGGcdTsdT sense
    287-306 8379 GCCCCCGGGGCCGCCGCCA 8380 GCCCCCGGGGCCGCCGCcAdTsdT antis
    288-307 8381 GGCGGCGGCCCCGGGGGCU 8382 GGcGGcGGccccGGGGGcudTsdT sense
    288-307 8383 AGCCCCCGGGGCCGCCGCC 8384 AGCCCCCGGGGCCGCCGCCdTsdT antis
    309-328 8385 GCCUCUGGCCCAGGAGGCA 8386 GccucuGGcccAGGAGGcAdTsdT sense
    309-328 8387 UGCCUCCUGGGCCAGAGGC 8388 UGCCUCCUGGGCcAGAGGCdTsdT antis
    310-329 8389 CCUCUGGCCCAGGAGGCAC 8390 ccucuGGcccAGGAGGcAcdTsdT sense
    310-329 8391 GUGCCUCCUGGGCCAGAGG 8392 GUGCCUCCUGGGCcAGAGGdTsdT antis
    312-331 8393 UCUGGCCCAGGAGGCACUG 8394 ucuGGcccAGGAGGcAcuGdTsdT sense
    312-331 8395 CAGUGCCUCCUGGGCCAGA 8396 cAGUGCCUCCUGGGCcAGAdTsdT antis
    313-332 8397 CUGGCCCAGGAGGCACUGG 8398 cuGGcccAGGAGGcAcuGGdTsdT sense
    313-332 8399 CCAGUGCCUCCUGGGCCAG 8400 CcAGUGCCUCCUGGGCcAGdTsdT antis
    315-334 8401 GGCCCAGGAGGCACUGGCG 8402 GGcccAGGAGGcAcuGGcGdTsdT sense
    315-334 8403 CGCCAGUGCCUCCUGGGCC 8404 CGCcAGUGCCUCCUGGGCCdTsdT antis
    356-375 8405 UAUGGGUGGGGGCGUGGGA 8406 uAuGGGuGGGGGcGuGGGAdTsdT sense
    356-375 8407 UCCCACGCCCCCACCCAUA 8408 UCCcACGCCCCcACCcAuAdTsdT antis
    359-378 8409 GGGUGGGGGCGUGGGAGCC 8410 GGGuGGGGGcGuGGGAGccdTsdT sense
    359-378 8411 GGCUCCCACGCCCCCACCC 8412 GGCUCCcACGCCCCcACCCdTsdT antis
    360-379 8413 GGUGGGGGCGUGGGAGCCU 8414 GGuGGGGGcGuGGGAGccudTsdT sense
    360-379 8415 AGGCUCCCACGCCCCCACC 8416 AGGCUCCcACGCCCCcACCdTsdT antis
    362-381 8417 UGGGGGCGUGGGAGCCUCG 8418 uGGGGGcGuGGGAGccucGdTsdT sense
    362-381 8419 CGAGGCUCCCACGCCCCCA 8420 CGAGGCUCCcACGCCCCcAdTsdT antis
    367-386 8421 GCGUGGGAGCCUCGAGCUC 8422 GcGuGGGAGccucGAGcucdTsdT sense
    367-386 8423 GAGCUCGAGGCUCCCACGC 8424 GAGCUCGAGGCUCCcACGCdTsdT antis
    401-420 8425 CGGCAGCGGCGGAGGAGGC 8426 cGGcAGcGGcGGAGGAGGcdTsdT sense
    401-420 8427 GCCUCCUCCGCCGCUGCCG 8428 GCCUCCUCCGCCGCUGCCGdTsdT antis
    402-421 8429 GGCAGCGGCGGAGGAGGCA 8430 GGcAGcGGcGGAGGAGGcAdTsdT sense
    402-421 8431 UGCCUCCUCCGCCGCUGCC 8432 UGCCUCCUCCGCCGCUGCCdTsdT antis
    409-428 8433 GCGGAGGAGGCAGCGGUGG 8434 GcGGAGGAGGcAGcGGuGGdTsdT sense
    409-428 8435 CCACCGCUGCCUCCUCCGC 8436 CcACCGCUGCCUCCUCCGCdTsdT antis
    410-429 8437 CGGAGGAGGCAGCGGUGGC 8438 cGGAGGAGGcAGcGGuGGcdTsdT sense
    410-429 8439 GCCACCGCUGCCUCCUCCG 8440 GCcACCGCUGCCUCCUCCGdTsdT antis
    415-434 8441 GAGGCAGCGGUGGCCCCGG 8442 GAGGcAGcGGuGGccccGGdTsdT sense
    415-434 8443 CCGGGGCCACCGCUGCCUC 8444 CCGGGGCcACCGCUGCCUCdTsdT antis
    416-435 8445 AGGCAGCGGUGGCCCCGGC 8446 AGGcAGcGGuGGccccGGcdTsdT sense
    416-435 8447 GCCGGGGCCACCGCUGCCU 8448 GCCGGGGCcACCGCUGCCUdTsdT antis
    483-502 8449 GGGAAGGUGACCACAGUGG 8450 GGGAAGGuGAccAcAGuGGdTsdT sense
    483-502 8451 CCACUGUGGUCACCUUCCC 8452 CcACUGUGGUcACCUUCCCdTsdT antis
    484-503 8453 GGAAGGUGACCACAGUGGU 8454 GGAAGGuGAccAcAGuGGudTsdT sense
    484-503 8455 ACCACUGUGGUCACCUUCC 8456 ACcACUGUGGUcACCUUCCdTsdT antis
    486-505 8457 AAGGUGACCACAGUGGUAG 8458 AAGGuGAccAcAGuGGuAGdTsdT sense
    486-505 8459 CUACCACUGUGGUCACCUU 8460 CuACcACUGUGGUcACCUUdTsdT antis
    529-548 8461 GUUCCCAAGAAGUGGCUUA 8462 GuucccAAGAAGuGGcuuAdTsdT sense
    529-548 8463 UAAGCCACUUCUUGGGAAC 8464 uAAGCcACUUCUUGGGAACdTsdT antis
    560-579 8465 AGUGAUUGGUAAUGGCUCA 8466 AGuGAuuGGuAAuGGcucAdTsdT sense
    560-579 8467 UGAGCCAUUACCAAUCACU 8468 UGAGCcAUuACcAAUcACUdTsdT antis
    561-580 8469 GUGAUUGGUAAUGGCUCAU 8470 GuGAuuGGuAAuGGcucAudTsdT sense
    561-580 8471 AUGAGCCAUUACCAAUCAC 8472 AUGAGCcAUuACcAAUcACdTsdT antis
    622-641 8473 UGGUGGCCAUCAAGAAGGU 8474 uGGuGGccAucAAGAAGGudTsdT sense
    622-641 8475 ACCUUCUUGAUGGCCACCA 8476 ACCUUCUUGAUGGCcACcAdTsdT antis
    628-647 8477 CCAUCAAGAAGGUUCUUCA 8478 ccAucAAGAAGGuucuucAdTsdT sense
    628-647 8479 UGAAGAACCUUCUUGAUGG 8480 UGAAGAACCUUCUUGAUGGdTsdT antis
    629-648 8481 CAUCAAGAAGGUUCUUCAG 8482 cAucAAGAAGGuucuucAGdTsdT sense
    629-648 8483 CUGAAGAACCUUCUUGAUG 8484 CUGAAGAACCUUCUUGAUGdTsdT antis
    637-656 8485 AGGUUCUUCAGGACAAAAG 8486 AGGuucuucAGGAcAAAAGdTsdT sense
    637-656 8487 CUUUUGUCCUGAAGAACCU 8488 CUUUUGUCCUGAAGAACCUdTsdT antis
    684-703 8489 CGUAAGCUGGACCACUGCA 8490 cGuAAGcuGGAccAcuGcAdTsdT sense
    684-703 8491 UGCAGUGGUCCAGCUUACG 8492 UGcAGUGGUCcAGCUuACGdTsdT antis
    695-714 8493 CCACUGCAAUAUUGUGAGG 8494 ccAcuGcAAuAuuGuGAGGdTsdT sense
    695-714 8495 CCUCACAAUAUUGCAGUGG 8496 CCUcAcAAuAUUGcAGUGGdTsdT antis
    719-738 8497 GUACUUUUUCUACUCCAGU 8498 GuAcuuuuucuAcuccAGudTsdT sense
    719-738 8499 ACUGGAGUAGAAAAAGUAC 8500 ACUGGAGuAGAAAAAGuACdTsdT antis
    722-741 8501 CUUUUUCUACUCCAGUGGG 8502 cuuuuucuAcuccAGuGGGdTsdT sense
    722-741 8503 CCCACUGGAGUAGAAAAAG 8504 CCcACUGGAGuAGAAAAAGdTsdT antis
    728-747 8505 CUACUCCAGUGGGGAGAAG 8506 cuAcuccAGuGGGGAGAAGdTsdT sense
    728-747 8507 CUUCUCCCCACUGGAGUAG 8508 CUUCUCCCcACUGGAGuAGdTsdT antis
    732-751 8509 UCCAGUGGGGAGAAGAAGG 8510 uccAGuGGGGAGAAGAAGGdTsdT sense
    732-751 8511 CCUUCUUCUCCCCACUGGA 8512 CCUUCUUCUCCCcACUGGAdTsdT antis
    734-753 8513 CAGUGGGGAGAAGAAGGAC 8514 cAGuGGGGAGAAGAAGGAcdTsdT sense
    734-753 8515 GUCCUUCUUCUCCCCACUG 8516 GUCCUUCUUCUCCCcACUGdTsdT antis
    735-754 8517 AGUGGGGAGAAGAAGGACG 8518 AGuGGGGAGAAGAAGGAcGdTsdT sense
    735-754 8519 CGUCCUUCUUCUCCCCACU 8520 CGUCCUUCUUCUCCCcACUdTsdT antis
    766-785 8521 AUCUGGUGCUGGAGUAUGU 8522 AucuGGuGcuGGAGuAuGudTsdT sense
    766-785 8523 ACAUACUCCAGCACCAGAU 8524 AcAuACUCcAGcACcAGAUdTsdT antis
    767-786 8525 UCUGGUGCUGGAGUAUGUG 8526 ucuGGuGcuGGAGuAuGuGdTsdT sense
    767-786 8527 CACAUACUCCAGCACCAGA 8528 cAcAuACUCcAGcACcAGAdTsdT antis
    768-787 8529 CUGGUGCUGGAGUAUGUGC 8530 cuGGuGcuGGAGuAuGuGcdTsdT sense
    768-787 8531 GCACAUACUCCAGCACCAG 8532 GcAcAuACUCcAGcACcAGdTsdT antis
    812-831 8533 CCACUUCACCAAGGCCAAG 8534 ccAcuucAccAAGGccAAGdTsdT sense
    812-831 8535 CUUGGCCUUGGUGAAGUGG 8536 CUUGGCCUUGGUGAAGUGGdTsdT antis
    814-833 8537 ACUUCACCAAGGCCAAGCU 8538 AcuucAccAAGGccAAGcudTsdT sense
    814-833 8539 AGCUUGGCCUUGGUGAAGU 8540 AGCUUGGCCUUGGUGAAGUdTsdT antis
    816-835 8541 UUCACCAAGGCCAAGCUGA 8542 uucAccAAGGccAAGcuGAdTsdT sense
    816-835 8543 UCAGCUUGGCCUUGGUGAA 8544 UcAGCUUGGCCUUGGUGAAdTsdT antis
    819-838 8545 ACCAAGGCCAAGCUGAUCA 8546 AccAAGGccAAGcuGAucAdTsdT sense
    819-838 8547 UGAUCAGCUUGGCCUUGGU 8548 UGAUcAGCUUGGCCUUGGUdTsdT antis
    820-839 8549 CCAAGGCCAAGCUGAUCAC 8550 ccAAGGccAAGcuGAucAcdTsdT sense
    820-839 8551 GUGAUCAGCUUGGCCUUGG 8552 GUGAUcAGCUUGGCCUUGGdTsdT antis
    864-883 8553 AUGUACCAGCUCUUCCGGA 8554 AuGuAccAGcucuuccGGAdTsdT sense
    864-883 8555 UCCGGAAGAGCUGGUACAU 8556 UCCGGAAGAGCUGGuAcAUdTsdT antis
    875-894 8557 CUUCCGGAGCUUGGCCUAC 8558 cuuccGGAGcuuGGccuAcdTsdT sense
    875-894 8559 GUAGGCCAAGCUCCGGAAG 8560 GuAGGCcAAGCUCCGGAAGdTsdT antis
    964-983 8561 UCCUCAAGCUCUGCGAUUU 8562 uccucAAGcucuGcGAuuudTsdT sense
    964-983 8563 AAAUCGCAGAGCUUGAGGA 8564 AAAUCGcAGAGCUUGAGGAdTsdT antis
    965-984 8565 CCUCAAGCUCUGCGAUUUU 8566 ccucAAGcucuGcGAuuuudTsdT sense
    965-984 8567 AAAAUCGCAGAGCUUGAGG 8568 AAAAUCGcAGAGCUUGAGGdTsdT antis
    969-988 8569 AAGCUCUGCGAUUUUGGCA 8570 AAGcucuGcGAuuuuGGcAdTsdT sense
    969-988 8571 UGCCAAAAUCGCAGAGCUU 8572 UGCcAAAAUCGcAGAGCUUdTsdT antis
    980-999 8573 UUUUGGCAGUGCAAAGCAG 8574 uuuuGGcAGuGcAAAGcAGdTsdT sense
    980-999 8575 CUGCUUUGCACUGCCAAAA 8576 CUGCUUUGcACUGCcAAAAdTsdT antis
     981-1000 8577 UUUGGCAGUGCAAAGCAGC 8578 uuuGGcAGuGcAAAGcAGcdTsdT sense
     981-1000 8579 GCUGCUUUGCACUGCCAAA 8580 GCUGCUUUGcACUGCcAAAdTsdT antis
     985-1004 8581 GCAGUGCAAAGCAGCUGGU 8582 GcAGuGcAAAGcAGcuGGudTsdT sense
     985-1004 8583 ACCAGCUGCUUUGCACUGC 8584 ACcAGCUGCUUUGcACUGCdTsdT antis
    1166-1185 8585 GGUGGACCAGCUUGUGGAG 8586 GGuGGAccAGcuuGuGGAGdTsdT sense
    1166-1185 8587 CUCCACAAGCUGGUCCACC 8588 CUCcAcAAGCUGGUCcACCdTsdT antis
    1167-1186 8589 GUGGACCAGCUUGUGGAGA 8590 GuGGAccAGcuuGuGGAGAdTsdT sense
    1167-1186 8591 UCUCCACAAGCUGGUCCAC 8592 UCUCcAcAAGCUGGUCcACdTsdT antis
    1171-1190 8593 ACCAGCUUGUGGAGAUCAU 8594 AccAGcuuGuGGAGAucAudTsdT sense
    1171-1190 8595 AUGAUCUCCACAAGCUGGU 8596 AUGAUCUCcAcAAGCUGGUdTsdT antis
    1211-1230 8597 CAGGGAACAAAUCCGAGAG 8598 cAGGGAAcAAAuccGAGAGdTsdT sense
    1211-1230 8599 CUCUCGGAUUUGUUCCCUG 8600 CUCUCGGAUUUGUUCCCUGdTsdT antis
    1254-1273 8601 AAGUUCCCCCAGAUCAAAG 8602 AAGuucccccAGAucAAAGdTsdT sense
    1254-1273 8603 CUUUGAUCUGGGGGAACUU 8604 CUUUGAUCUGGGGGAACUUdTsdT antis
    1259-1278 8605 CCCCCAGAUCAAAGCUCAC 8606 cccccAGAucAAAGcucAcdTsdT sense
    1259-1278 8607 GUGAGCUUUGAUCUGGGGG 8608 GUGAGCUUUGAUCUGGGGGdTsdT antis
    1260-1279 8609 CCCCAGAUCAAAGCUCACC 8610 ccccAGAucAAAGcucAccdTsdT sense
    1260-1279 8611 GGUGAGCUUUGAUCUGGGG 8612 GGUGAGCUUUGAUCUGGGGdTsdT antis
    1281-1300 8613 UGGACAAAGGUGUUCAAAU 8614 uGGAcAAAGGuGuucAAAudTsdT sense
    1281-1300 8615 AUUUGAACACCUUUGUCCA 8616 AUUUGAAcACCUUUGUCcAdTsdT antis
    1360-1379 8617 CCUCAAGGCUCUCCCCACU 8618 ccucAAGGcucuccccAcudTsdT sense
    1360-1379 8619 AGUGGGGAGAGCCUUGAGG 8620 AGUGGGGAGAGCCUUGAGGdTsdT antis
    1381-1400 8621 AGGCUUGUGCCCACAGCUU 8622 AGGcuuGuGcccAcAGcuudTsdT sense
    1381-1400 8623 AAGCUGUGGGCACAAGCCU 8624 AAGCUGUGGGcAcAAGCCUdTsdT antis
    1385-1404 8625 UUGUGCCCACAGCUUCUUC 8626 uuGuGcccAcAGcuucuucdTsdT sense
    1385-1404 8627 GAAGAAGCUGUGGGCACAA 8628 GAAGAAGCUGUGGGcAcAAdTsdT antis
    1387-1406 8629 GUGCCCACAGCUUCUUCGA 8630 GuGcccAcAGcuucuucGAdTsdT sense
    1387-1406 8631 UCGAAGAAGCUGUGGGCAC 8632 UCGAAGAAGCUGUGGGcACdTsdT antis
    1388-1407 8633 UGCCCACAGCUUCUUCGAU 8634 uGcccAcAGcuucuucGAudTsdT sense
    1388-1407 8635 AUCGAAGAAGCUGUGGGCA 8636 AUCGAAGAAGCUGUGGGcAdTsdT antis
    1455-1474 8637 CCCCUGUUCAACUUCAGUC 8638 ccccuGuucAAcuucAGucdTsdT sense
    1455-1474 8639 GACUGAAGUUGAACAGGGG 8640 GACUGAAGUUGAAcAGGGGdTsdT antis
    1456-1475 8641 CCCUGUUCAACUUCAGUCC 8642 cccuGuucAAcuucAGuccdTsdT sense
    1456-1475 8643 GGACUGAAGUUGAACAGGG 8644 GGACUGAAGUUGAAcAGGGdTsdT antis
    1457-1476 8645 CCUGUUCAACUUCAGUCCU 8646 ccuGuucAAcuucAGuccudTsdT sense
    1457-1476 8647 AGGACUGAAGUUGAACAGG 8648 AGGACUGAAGUUGAAcAGGdTsdT antis
    1458-1477 8649 CUGUUCAACUUCAGUCCUG 8650 cuGuucAAcuucAGuccuGdTsdT sense
    1458-1477 8651 CAGGACUGAAGUUGAACAG 8652 cAGGACUGAAGUUGAAcAGdTsdT antis
    1513-1532 8653 UCAUCCCUCCUCACUUGAG 8654 ucAucccuccucAcuuGAGdTsdT sense
    1513-1532 8655 CUCAAGUGAGGAGGGAUGA 8656 CUcAAGUGAGGAGGGAUGAdTsdT antis
    1514-1533 8657 CAUCCCUCCUCACUUGAGG 8658 cAucccuccucAcuuGAGGdTsdT sense
    1514-1533 8659 CCUCAAGUGAGGAGGGAUG 8660 CCUcAAGUGAGGAGGGAUGdTsdT antis
    1517-1536 8661 CCCUCCUCACUUGAGGUCC 8662 cccuccucAcuuGAGGuccdTsdT sense
    1517-1536 8663 GGACCUCAAGUGAGGAGGG 8664 GGACCUcAAGUGAGGAGGGdTsdT antis
    1518-1537 8665 CCUCCUCACUUGAGGUCCC 8666 ccuccucAcuuGAGGucccdTsdT sense
    1518-1537 8667 GGGACCUCAAGUGAGGAGG 8668 GGGACCUcAAGUGAGGAGGdTsdT antis
    1519-1538 8669 CUCCUCACUUGAGGUCCCC 8670 cuccucAcuuGAGGuccccdTsdT sense
    1519-1538 8671 GGGGACCUCAAGUGAGGAG 8672 GGGGACCUcAAGUGAGGAGdTsdT antis
    1525-1544 8673 ACUUGAGGUCCCCAGCAGG 8674 AcuuGAGGuccccAGcAGGdTsdT sense
    1525-1544 8675 CCUGCUGGGGACCUCAAGU 8676 CCUGCUGGGGACCUcAAGUdTsdT antis
    1526-1545 8677 CUUGAGGUCCCCAGCAGGC 8678 cuuGAGGuccccAGcAGGcdTsdT sense
    1526-1545 8679 GCCUGCUGGGGACCUCAAG 8680 GCCUGCUGGGGACCUcAAGdTsdT antis
    1527-1546 8681 UUGAGGUCCCCAGCAGGCC 8682 uuGAGGuccccAGcAGGccdTsdT sense
    1527-1546 8683 GGCCUGCUGGGGACCUCAA 8684 GGCCUGCUGGGGACCUcAAdTsdT antis
    1530-1549 8685 AGGUCCCCAGCAGGCCCUG 8686 AGGuccccAGcAGGcccuGdTsdT sense
    1530-1549 8687 CAGGGCCUGCUGGGGACCU 8688 cAGGGCCUGCUGGGGACCUdTsdT antis
    1531-1550 8689 GGUCCCCAGCAGGCCCUGC 8690 GGuccccAGcAGGcccuGcdTsdT sense
    1531-1550 8691 GCAGGGCCUGCUGGGGACC 8692 GcAGGGCCUGCUGGGGACCdTsdT antis
    1532-1551 8693 GUCCCCAGCAGGCCCUGCU 8694 GuccccAGcAGGcccuGcudTsdT sense
    1532-1551 8695 AGCAGGGCCUGCUGGGGAC 8696 AGcAGGGCCUGCUGGGGACdTsdT antis
    1538-1557 8697 AGCAGGCCCUGCUUCUCCC 8698 AGcAGGcccuGcuucucccdTsdT sense
    1538-1557 8699 GGGAGAAGCAGGGCCUGCU 8700 GGGAGAAGcAGGGCCUGCUdTsdT antis
    1588-1607 8701 CUUUAACUGAAGCUCAGAC 8702 cuuuAAcuGAAGcucAGAcdTsdT sense
    1588-1607 8703 GUCUGAGCUUCAGUUAAAG 8704 GUCUGAGCUUcAGUuAAAGdTsdT antis
    1626-1645 8705 UCUGAUGCCACAACUGCUA 8706 ucuGAuGccAcAAcuGcuAdTsdT sense
    1626-1645 8707 UAGCAGUUGUGGCAUCAGA 8708 uAGcAGUUGUGGcAUcAGAdTsdT antis
    1627-1646 8709 CUGAUGCCACAACUGCUAC 8710 cuGAuGccAcAAcuGcuAcdTsdT sense
    1627-1646 8711 GUAGCAGUUGUGGCAUCAG 8712 GuAGcAGUUGUGGcAUcAGdTsdT antis
    1628-1647 8713 UGAUGCCACAACUGCUACC 8714 uGAuGccAcAAcuGcuAccdTsdT sense
    1628-1647 8715 GGUAGCAGUUGUGGCAUCA 8716 GGuAGcAGUUGUGGcAUcAdTsdT antis
    1629-1648 8717 GAUGCCACAACUGCUACCC 8718 GAuGccAcAAcuGcuAcccdTsdT sense
    1629-1648 8719 GGGUAGCAGUUGUGGCAUC 8720 GGGuAGcAGUUGUGGcAUCdTsdT antis
    1686-1705 8721 CACGUCCAUCUGGGAAGGC 8722 cAcGuccAucuGGGAAGGcdTsdT sense
    1686-1705 8723 GCCUUCCCAGAUGGACGUG 8724 GCCUUCCcAGAUGGACGUGdTsdT antis
    1687-1706 8725 ACGUCCAUCUGGGAAGGCC 8726 AcGuccAucuGGGAAGGccdTsdT sense
    1687-1706 8727 GGCCUUCCCAGAUGGACGU 8728 GGCCUUCCcAGAUGGACGUdTsdT antis
    1688-1707 8729 CGUCCAUCUGGGAAGGCCC 8730 cGuccAucuGGGAAGGcccdTsdT sense
    1688-1707 8731 GGGCCUUCCCAGAUGGACG 8732 GGGCCUUCCcAGAUGGACGdTsdT antis
    1689-1708 8733 GUCCAUCUGGGAAGGCCCA 8734 GuccAucuGGGAAGGcccAdTsdT sense
    1689-1708 8735 UGGGCCUUCCCAGAUGGAC 8736 UGGGCCUUCCcAGAUGGACdTsdT antis
    1694-1713 8737 UCUGGGAAGGCCCAAGUGG 8738 ucuGGGAAGGcccAAGuGGdTsdT sense
    1694-1713 8739 CCACUUGGGCCUUCCCAGA 8740 CcACUUGGGCCUUCCcAGAdTsdT antis
    1695-1714 8741 CUGGGAAGGCCCAAGUGGC 8742 cuGGGAAGGcccAAGuGGcdTsdT sense
    1695-1714 8743 GCCACUUGGGCCUUCCCAG 8744 GCcACUUGGGCCUUCCcAGdTsdT antis
    1709-1728 8745 GUGGCGCUGGGAAGGGGGC 8746 GuGGcGcuGGGAAGGGGGcdTsdT sense
    1709-1728 8747 GCCCCCUUCCCAGCGCCAC 8748 GCCCCCUUCCcAGCGCcACdTsdT antis
    1714-1733 8749 GCUGGGAAGGGGGCCACAG 8750 GcuGGGAAGGGGGccAcAGdTsdT sense
    1714-1733 8751 CUGUGGCCCCCUUCCCAGC 8752 CUGUGGCCCCCUUCCcAGCdTsdT antis
    1722-1741 8753 GGGGGCCACAGCCCAUCAA 8754 GGGGGccAcAGcccAucAAdTsdT sense
    1722-1741 8755 UUGAUGGGCUGUGGCCCCC 8756 UUGAUGGGCUGUGGCCCCCdTsdT antis
    1723-1742 8757 GGGGCCACAGCCCAUCAAG 8758 GGGGccAcAGcccAucAAGdTsdT sense
    1723-1742 8759 CUUGAUGGGCUGUGGCCCC 8760 CUUGAUGGGCUGUGGCCCCdTsdT antis
    1732-1751 8761 GCCCAUCAAGCUCCUGCCC 8762 GcccAucAAGcuccuGcccdTsdT sense
    1732-1751 8763 GGGCAGGAGCUUGAUGGGC 8764 GGGcAGGAGCUUGAUGGGCdTsdT antis
    1737-1756 8765 UCAAGCUCCUGCCCUGGCU 8766 ucAAGcuccuGcccuGGcudTsdT sense
    1737-1756 8767 AGCCAGGGCAGGAGCUUGA 8768 AGCcAGGGcAGGAGCUUGAdTsdT antis
    1743-1762 8769 UCCUGCCCUGGCUGGGCCC 8770 uccuGcccuGGcuGGGcccdTsdT sense
    1743-1762 8771 GGGCCCAGCCAGGGCAGGA 8772 GGGCCcAGCcAGGGcAGGAdTsdT antis
    1744-1763 8773 CCUGCCCUGGCUGGGCCCC 8774 ccuGcccuGGcuGGGccccdTsdT sense
    1744-1763 8775 GGGGCCCAGCCAGGGCAGG 8776 GGGGCCcAGCcAGGGcAGGdTsdT antis
    1746-1765 8777 UGCCCUGGCUGGGCCCCUA 8778 uGcccuGGcuGGGccccuAdTsdT sense
    1746-1765 8779 UAGGGGCCCAGCCAGGGCA 8780 uAGGGGCCcAGCcAGGGcAdTsdT antis
    1748-1767 8781 CCCUGGCUGGGCCCCUAGA 8782 cccuGGcuGGGccccuAGAdTsdT sense
    1748-1767 8783 UCUAGGGGCCCAGCCAGGG 8784 UCuAGGGGCCcAGCcAGGGdTsdT antis
    1769-1788 8785 AGAGGGCAGAGGUAAAUGA 8786 AGAGGGcAGAGGuAAAuGAdTsdT sense
    1769-1788 8787 UCAUUUACCUCUGCCCUCU 8788 UcAUUuACCUCUGCCCUCUdTsdT antis
    1770-1789 8789 GAGGGCAGAGGUAAAUGAA 8790 GAGGGcAGAGGuAAAuGAAdTsdT sense
    1770-1789 8791 UUCAUUUACCUCUGCCCUC 8792 UUcAUUuACCUCUGCCCUCdTsdT antis
    1798-1817 8793 GCAUCUAGGCCUCCCUCAG 8794 GcAucuAGGccucccucAGdTsdT sense
    1798-1817 8795 CUGAGGGAGGCCUAGAUGC 8796 CUGAGGGAGGCCuAGAUGCdTsdT antis
    1825-1844 8797 CCUCUGUGGUGGGCUUUUU 8798 ccucuGuGGuGGGcuuuuudTsdT sense
    1825-1844 8799 AAAAAGCCCACCACAGAGG 8800 AAAAAGCCcACcAcAGAGGdTsdT antis
    1831-1850 8801 UGGUGGGCUUUUUAAAGAG 8802 uGGuGGGcuuuuuAAAGAGdTsdT sense
    1831-1850 8803 CUCUUUAAAAAGCCCACCA 8804 CUCUUuAAAAAGCCcACcAdTsdT antis
    1833-1852 8805 GUGGGCUUUUUAAAGAGGA 8806 GuGGGcuuuuuAAAGAGGAdTsdT sense
    1833-1852 8807 UCCUCUUUAAAAAGCCCAC 8808 UCCUCUUuAAAAAGCCcACdTsdT antis
    1837-1856 8809 GCUUUUUAAAGAGGAUUUU 8810 GcuuuuuAAAGAGGAuuuudTsdT sense
    1837-1856 8811 AAAAUCCUCUUUAAAAAGC 8812 AAAAUCCUCUUuAAAAAGCdTsdT antis
    1838-1857 8813 CUUUUUAAAGAGGAUUUUA 8814 cuuuuuAAAGAGGAuuuuAdTsdT sense
    1838-1857 8815 UAAAAUCCUCUUUAAAAAG 8816 uAAAAUCCUCUUuAAAAAGdTsdT antis
    1869-1888 8817 GGAGGGGAGAAAAGGAAGG 8818 GGAGGGGAGAAAAGGAAGGdTsdT sense
    1869-1888 8819 CCUUCCUUUUCUCCCCUCC 8820 CCUUCCUUUUCUCCCCUCCdTsdT antis
    1870-1889 8821 GAGGGGAGAAAAGGAAGGA 8822 GAGGGGAGAAAAGGAAGGAdTsdT sense
    1870-1889 8823 UCCUUCCUUUUCUCCCCUC 8824 UCCUUCCUUUUCUCCCCUCdTsdT antis
    1888-1907 8825 ACGGGGUUUGGGGGUGUGA 8826 AcGGGGuuuGGGGGuGuGAdTsdT sense
    1888-1907 8827 UCACACCCCCAAACCCCGU 8828 UcAcACCCCcAAACCCCGUdTsdT antis
    1923-1942 8829 UGGUCCCCUCCCCUCCCCC 8830 uGGuccccuccccucccccdTsdT sense
    1923-1942 8831 GGGGGAGGGGAGGGGACCA 8832 GGGGGAGGGGAGGGGACcAdTsdT antis
    1924-1943 8833 GGUCCCCUCCCCUCCCCCA 8834 GGuccccuccccucccccAdTsdT sense
    1924-1943 8835 UGGGGGAGGGGAGGGGACC 8836 UGGGGGAGGGGAGGGGACCdTsdT antis
    1931-1950 8837 UCCCCUCCCCCAGGCUACC 8838 uccccucccccAGGcuAccdTsdT sense
    1931-1950 8839 GGUAGCCUGGGGGAGGGGA 8840 GGuAGCCUGGGGGAGGGGAdTsdT antis
    1962-1981 8841 CCCCCCUCUCCCAGGUCCC 8842 ccccccucucccAGGucccdTsdT sense
    1962-1981 8843 GGGACCUGGGAGAGGGGGG 8844 GGGACCUGGGAGAGGGGGGdTsdT antis
    1963-1982 8845 CCCCCUCUCCCAGGUCCCU 8846 cccccucucccAGGucccudTsdT sense
    1963-1982 8847 AGGGACCUGGGAGAGGGGG 8848 AGGGACCUGGGAGAGGGGGdTsdT antis
    2132-2151 8849 CCAAGGCUUCCUCCCUCUC 8850 ccAAGGcuuccucccucucdTsdT sense
    2132-2151 8851 GAGAGGGAGGAAGCCUUGG 8852 GAGAGGGAGGAAGCCUUGGdTsdT antis
    2139-2158 8853 UUCCUCCCUCUCCCCAUCC 8854 uuccucccucuccccAuccdTsdT sense
    2139-2158 8855 GGAUGGGGAGAGGGAGGAA 8856 GGAUGGGGAGAGGGAGGAAdTsdT antis
    63-82 8857 UGGGCCGGAGCCGGAGCCC 8858 uGGGccGGAGccGGAGcccdTsdT sense
    63-82 8859 GGGCUCCGGCUCCGGCCCA 8860 GGGCUCCGGCUCCGGCCcAdTsdT antis
    65-84 8861 GGCCGGAGCCGGAGCCCGA 8862 GGccGGAGccGGAGcccGAdTsdT sense
    65-84 8863 UCGGGCUCCGGCUCCGGCC 8864 UCGGGCUCCGGCUCCGGCCdTsdT antis
    66-85 8865 GCCGGAGCCGGAGCCCGAA 8866 GccGGAGccGGAGcccGAAdTsdT sense
    66-85 8867 UUCGGGCUCCGGCUCCGGC 8868 UUCGGGCUCCGGCUCCGGCdTsdT antis
    115-134 8869 GGGAGGCGGCGGCAGAGGC 8870 GGGAGGcGGcGGcAGAGGcdTsdT sense
    115-134 8871 GCCUCUGCCGCCGCCUCCC 8872 GCCUCUGCCGCCGCCUCCCdTsdT antis
    118-137 8873 AGGCGGCGGCAGAGGCAGC 8874 AGGcGGcGGcAGAGGcAGcdTsdT sense
    118-137 8875 GCUGCCUCUGCCGCCGCCU 8876 GCUGCCUCUGCCGCCGCCUdTsdT antis
    119-138 8877 GGCGGCGGCAGAGGCAGCG 8878 GGcGGcGGcAGAGGcAGcGdTsdT sense
    119-138 8879 CGCUGCCUCUGCCGCCGCC 8880 CGCUGCCUCUGCCGCCGCCdTsdT antis
    128-147 8881 AGAGGCAGCGGCGGGGGCA 8882 AGAGGcAGcGGcGGGGGcAdTsdT sense
    128-147 8883 UGCCCCCGCCGCUGCCUCU 8884 UGCCCCCGCCGCUGCCUCUdTsdT antis
    129-148 8885 GAGGCAGCGGCGGGGGCAG 8886 GAGGcAGcGGcGGGGGcAGdTsdT sense
    129-148 8887 CUGCCCCCGCCGCUGCCUC 8888 CUGCCCCCGCCGCUGCCUCdTsdT antis
    265-284 8889 CAGGAGGCGGAGGCGGAGG 8890 cAGGAGGcGGAGGcGGAGGdTsdT sense
    265-284 8891 CCUCCGCCUCCGCCUCCUG 8892 CCUCCGCCUCCGCCUCCUGdTsdT antis
    266-285 8893 AGGAGGCGGAGGCGGAGGU 8894 AGGAGGcGGAGGcGGAGGudTsdT sense
    266-285 8895 ACCUCCGCCUCCGCCUCCU 8896 ACCUCCGCCUCCGCCUCCUdTsdT antis
    269-288 8897 AGGCGGAGGCGGAGGUGGU 8898 AGGcGGAGGcGGAGGuGGudTsdT sense
    269-288 8899 ACCACCUCCGCCUCCGCCU 8900 ACcACCUCCGCCUCCGCCUdTsdT antis
    275-294 8901 AGGCGGAGGUGGUGGCGGC 8902 AGGcGGAGGuGGuGGcGGcdTsdT sense
    275-294 8903 GCCGCCACCACCUCCGCCU 8904 GCCGCcACcACCUCCGCCUdTsdT antis
    278-297 8905 CGGAGGUGGUGGCGGCGGC 8906 cGGAGGuGGuGGcGGcGGcdTsdT sense
    278-297 8907 GCCGCCGCCACCACCUCCG 8908 GCCGCCGCcACcACCUCCGdTsdT antis
    279-298 8909 GGAGGUGGUGGCGGCGGCC 8910 GGAGGuGGuGGcGGcGGccdTsdT sense
    279-298 8911 GGCCGCCGCCACCACCUCC 8912 GGCCGCCGCcACcACCUCCdTsdT antis
    314-333 8913 UGGCCCAGGAGGCACUGGC 8914 uGGcccAGGAGGcAcuGGcdTsdT sense
    314-333 8915 GCCAGUGCCUCCUGGGCCA 8916 GCcAGUGCCUCCUGGGCcAdTsdT antis
    399-418 8917 AGCGGCAGCGGCGGAGGAG 8918 AGcGGcAGcGGcGGAGGAGdTsdT sense
    399-418 8919 CUCCUCCGCCGCUGCCGCU 8920 CUCCUCCGCCGCUGCCGCUdTsdT antis
    411-430 8921 GGAGGAGGCAGCGGUGGCC 8922 GGAGGAGGcAGcGGuGGccdTsdT sense
    411-430 8923 GGCCACCGCUGCCUCCUCC 8924 GGCcACCGCUGCCUCCUCCdTsdT antis
    412-431 8925 GAGGAGGCAGCGGUGGCCC 8926 GAGGAGGcAGcGGuGGcccdTsdT sense
    412-431 8927 GGGCCACCGCUGCCUCCUC 8928 GGGCcACCGCUGCCUCCUCdTsdT antis
    413-432 8929 AGGAGGCAGCGGUGGCCCC 8930 AGGAGGcAGcGGuGGccccdTsdT sense
    413-432 8931 GGGGCCACCGCUGCCUCCU 8932 GGGGCcACCGCUGCCUCCUdTsdT antis
    414-433 8933 GGAGGCAGCGGUGGCCCCG 8934 GGAGGcAGcGGuGGccccGdTsdT sense
    414-433 8935 CGGGGCCACCGCUGCCUCC 8936 CGGGGCcACCGCUGCCUCCdTsdT antis
    636-655 8937 AAGGUUCUUCAGGACAAAA 8938 AAGGuucuucAGGAcAAAAdTsdT sense
    636-655 8939 UUUUGUCCUGAAGAACCUU 8940 UUUUGUCCUGAAGAACCUUdTsdT antis
    731-750 8941 CUCCAGUGGGGAGAAGAAG 8942 cuccAGuGGGGAGAAGAAGdTsdT sense
    731-750 8943 CUUCUUCUCCCCACUGGAG 8944 CUUCUUCUCCCcACUGGAGdTsdT antis
    733-752 8945 CCAGUGGGGAGAAGAAGGA 8946 ccAGuGGGGAGAAGAAGGAdTsdT sense
    733-752 8947 UCCUUCUUCUCCCCACUGG 8948 UCCUUCUUCUCCCcACUGGdTsdT antis
    963-982 8949 GUCCUCAAGCUCUGCGAUU 8950 GuccucAAGcucuGcGAuudTsdT sense
    963-982 8951 AAUCGCAGAGCUUGAGGAC 8952 AAUCGcAGAGCUUGAGGACdTsdT antis
    1535-1554 8953 CCCAGCAGGCCCUGCUUCU 8954 cccAGcAGGcccuGcuucudTsdT sense
    1535-1554 8955 AGAAGCAGGGCCUGCUGGG 8956 AGAAGcAGGGCCUGCUGGGdTsdT antis
    1536-1555 8957 CCAGCAGGCCCUGCUUCUC 8958 ccAGcAGGcccuGcuucucdTsdT sense
    1536-1555 8959 GAGAAGCAGGGCCUGCUGG 8960 GAGAAGcAGGGCCUGCUGGdTsdT antis
    1537-1556 8961 CAGCAGGCCCUGCUUCUCC 8962 cAGcAGGcccuGcuucuccdTsdT sense
    1537-1556 8963 GGAGAAGCAGGGCCUGCUG 8964 GGAGAAGcAGGGCCUGCUGdTsdT antis
    1887-1906 8965 GACGGGGUUUGGGGGUGUG 8966 GAcGGGGuuuGGGGGuGuGdTsdT sense
    1887-1906 8967 CACACCCCCAAACCCCGUC 8968 cAcACCCCcAAACCCCGUCdTsdT antis
    1925-1944 8969 GUCCCCUCCCCUCCCCCAG 8970 GuccccuccccucccccAGdTsdT sense
    1925-1944 8971 CUGGGGGAGGGGAGGGGAC 8972 CUGGGGGAGGGGAGGGGACdTsdT antis
    1926-1945 8973 UCCCCUCCCCUCCCCCAGG 8974 uccccuccccucccccAGGdTsdT sense
    1926-1945 8975 CCUGGGGGAGGGGAGGGGA 8976 CCUGGGGGAGGGGAGGGGAdTsdT antis
    2055-2074 8977 AUUUUUUCUUAAAGAAAAC 8978 AuuuuuucuuAAAGAAAAcdTsdT sense
    2055-2074 8979 GUUUUCUUUAAGAAAAAAU 8980 GUUUUCUUuAAGAAAAAAUdTsdT antis
    2143-2162 8981 UCCCUCUCCCCAUCCUGGA 8982 ucccucuccccAuccuGGAdTsdT sense
    2143-2162 8983 UCCAGGAUGGGGAGAGGGA 8984 UCcAGGAUGGGGAGAGGGAdTsdT antis
  • TABLE 2
    Sequences of duplexes targeting Mouse GSK3-beta
    Sequences of duplexes targeting mouse GSK3-beta. Target sequence
    location identifies target sequence in mouse GSK3-beta mRNA NM_019827.6.
    Sense strand is identical to target sequence. Antisense strand is
    complementary to target sequence.
    Target SEQ SEQ
    sequence ID Unmodified sequence ID Modified sequence
    location NO: 5′ to 3′ NO: 5′ to 3′ Strand
    1842-1861 8985 ACUGUAACAUAGUCCGACU 10985 AcuGuAAcAuAGuccGAcudTsdT sense
    1842-1861 8986 AGUCGGACUAUGUUACAGU 10986 AGUCGGACuAUGUuAcAGUdTsdT antis
    1843-1862 8987 CUGUAACAUAGUCCGACUG 10987 cuGuAAcAuAGuccGAcuGdTsdT sense
    1843-1862 8988 CAGUCGGACUAUGUUACAG 10988 cAGUCGGACuAUGUuAcAGdTsdT antis
    1952-1971 8989 GCCAGACACUAUAGUCGAG 10989 GccAGAcAcuAuAGucGAGdTsdT sense
    1952-1971 8990 CUCGACUAUAGUGUCUGGC 10990 CUCGACuAuAGUGUCUGGCdTsdT antis
    1847-1866 8991 AACAUAGUCCGACUGCGGU 10991 AAcAuAGuccGAcuGcGGudTsdT sense
    1847-1866 8992 ACCGCAGUCGGACUAUGUU 10992 ACCGcAGUCGGACuAUGUUdTsdT antis
    1838-1857 8993 GACCACUGUAACAUAGUCC 10993 GAccAcuGuAAcAuAGuccdTsdT sense
    1838-1857 8994 GGACUAUGUUACAGUGGUC 10994 GGACuAUGUuAcAGUGGUCdTsdT antis
    1846-1865 8995 UAACAUAGUCCGACUGCGG 10995 uAAcAuAGuccGAcuGcGGdTsdT sense
    1846-1865 8996 CCGCAGUCGGACUAUGUUA 10996 CCGcAGUCGGACuAUGUuAdTsdT antis
    1849-1868 8997 CAUAGUCCGACUGCGGUAU 10997 cAuAGuccGAcuGcGGuAudTsdT sense
    1849-1868 8998 AUACCGCAGUCGGACUAUG 10998 AuACCGcAGUCGGACuAUGdTsdT antis
    1955-1974 8999 AGACACUAUAGUCGAGCCA 10999 AGAcAcuAuAGucGAGccAdTsdT sense
    1955-1974 9000 UGGCUCGACUAUAGUGUCU 11000 UGGCUCGACuAuAGUGUCUdTsdT antis
    1957-1976 9001 ACACUAUAGUCGAGCCAAG 11001 AcAcuAuAGucGAGccAAGdTsdT sense
    1957-1976 9002 CUUGGCUCGACUAUAGUGU 11002 CUUGGCUCGACuAuAGUGUdTsdT antis
    2169-2188 9003 CAUAUAUCUGUUCUCGGUA 11003 cAuAuAucuGuucucGGuAdTsdT sense
    2169-2188 9004 UACCGAGAACAGAUAUAUG 11004 uACCGAGAAcAGAuAuAUGdTsdT antis
    1788-1807 9005 UACAGGACAAGCGAUUUAA 11005 uAcAGGAcAAGcGAuuuAAdTsdT sense
    1788-1807 9006 UUAAAUCGCUUGUCCUGUA 11006 UuAAAUCGCUUGUCCUGuAdTsdT antis
    1862-1881 9007 CGGUAUUUCUUCUACUCGA 11007 cGGuAuuucuucuAcucGAdTsdT sense
    1862-1881 9008 UCGAGUAGAAGAAAUACCG 11008 UCGAGuAGAAGAAAuACCGdTsdT antis
    2021-2040 9009 UUCAGAAGUCUAGCCUAUA 11009 uucAGAAGucuAGccuAuAdTsdT sense
    2021-2040 9010 UAUAGGCUAGACUUCUGAA 11010 uAuAGGCuAGACUUCUGAAdTsdT antis
    1863-1882 9011 GGUAUUUCUUCUACUCGAG 11011 GGuAuuucuucuAcucGAGdTsdT sense
    1863-1882 9012 CUCGAGUAGAAGAAAUACC 11012 CUCGAGuAGAAGAAAuACCdTsdT antis
    2496-2515 9013 CACCUACCGCCCGGCUAAC 11013 cAccuAccGcccGGcuAAcdTsdT sense
    2496-2515 9014 GUUAGCCGGGCGGUAGGUG 11014 GUuAGCCGGGCGGuAGGUGdTsdT antis
    1796-1815 9015 AAGCGAUUUAAGAACCGAG 11015 AAGcGAuuuAAGAAccGAGdTsdT sense
    1796-1815 9016 CUCGGUUCUUAAAUCGCUU 11016 CUCGGUUCUuAAAUCGCUUdTsdT antis
    1844-1863 9017 UGUAACAUAGUCCGACUGC 11017 uGuAAcAuAGuccGAcuGcdTsdT sense
    1844-1863 9018 GCAGUCGGACUAUGUUACA 11018 GcAGUCGGACuAUGUuAcAdTsdT antis
    2221-2240 9019 UGAUUACACGUCCAGUAUA 11019 uGAuuAcAcGuccAGuAuAdTsdT sense
    2221-2240 9020 UAUACUGGACGUGUAAUCA 11020 uAuACUGGACGUGuAAUcAdTsdT antis
    2228-2247 9021 ACGUCCAGUAUAGAUGUAU 11021 AcGuccAGuAuAGAuGuAudTsdT sense
    2228-2247 9022 AUACAUCUAUACUGGACGU 11022 AuAcAUCuAuACUGGACGUdTsdT antis
    1697-1716 9023 GACACGAAAGUGAUUGGAA 11023 GAcAcGAAAGuGAuuGGAAdTsdT sense
    1697-1716 9024 UUCCAAUCACUUUCGUGUC 11024 UUCcAAUcACUUUCGUGUCdTsdT antis
    1845-1864 9025 GUAACAUAGUCCGACUGCG 11025 GuAAcAuAGuccGAcuGcGdTsdT sense
    1845-1864 9026 CGCAGUCGGACUAUGUUAC 11026 CGcAGUCGGACuAUGUuACdTsdT antis
    1851-1870 9027 UAGUCCGACUGCGGUAUUU 11027 uAGuccGAcuGcGGuAuuudTsdT sense
    1851-1870 9028 AAAUACCGCAGUCGGACUA 11028 AAAuACCGcAGUCGGACuAdTsdT antis
    1871-1890 9029 UUCUACUCGAGUGGUGAGA 11029 uucuAcucGAGuGGuGAGAdTsdT sense
    1871-1890 9030 UCUCACCACUCGAGUAGAA 11030 UCUcACcACUCGAGuAGAAdTsdT antis
    2022-2041 9031 UCAGAAGUCUAGCCUAUAU 11031 ucAGAAGucuAGccuAuAudTsdT sense
    2022-2041 9032 AUAUAGGCUAGACUUCUGA 11032 AuAuAGGCuAGACUUCUGAdTsdT antis
    2024-2043 9033 AGAAGUCUAGCCUAUAUCC 11033 AGAAGucuAGccuAuAuccdTsdT sense
    2024-2043 9034 GGAUAUAGGCUAGACUUCU 11034 GGAuAuAGGCuAGACUUCUdTsdT antis
    2220-2239 9035 CUGAUUACACGUCCAGUAU 11035 cuGAuuAcAcGuccAGuAudTsdT sense
    2220-2239 9036 AUACUGGACGUGUAAUCAG 11036 AuACUGGACGUGuAAUcAGdTsdT antis
    1789-1808 9037 ACAGGACAAGCGAUUUAAG 11037 AcAGGAcAAGcGAuuuAAGdTsdT sense
    1789-1808 9038 CUUAAAUCGCUUGUCCUGU 11038 CUuAAAUCGCUUGUCCUGUdTsdT antis
    1922-1941 9039 GACUAUGUUCCGGAGACAG 11039 GAcuAuGuuccGGAGAcAGdTsdT sense
    1922-1941 9040 CUGUCUCCGGAACAUAGUC 11040 CUGUCUCCGGAAcAuAGUCdTsdT antis
    2020-2039 9041 GUUCAGAAGUCUAGCCUAU 11041 GuucAGAAGucuAGccuAudTsdT sense
    2020-2039 9042 AUAGGCUAGACUUCUGAAC 11042 AuAGGCuAGACUUCUGAACdTsdT antis
    2492-2511 9043 UACACACCUACCGCCCGGC 11043 uAcAcAccuAccGcccGGcdTsdT sense
    2492-2511 9044 GCCGGGCGGUAGGUGUGUA 11044 GCCGGGCGGuAGGUGUGuAdTsdT antis
    1678-1697 9045 ACAGGAAGUCAGUUAUACA 11045 AcAGGAAGucAGuuAuAcAdTsdT sense
    1678-1697 9046 UGUAUAACUGACUUCCUGU 11046 UGuAuAACUGACUUCCUGUdTsdT antis
    1840-1859 9047 CCACUGUAACAUAGUCCGA 11047 ccAcuGuAAcAuAGuccGAdTsdT sense
    1840-1859 9048 UCGGACUAUGUUACAGUGG 11048 UCGGACuAUGUuAcAGUGGdTsdT antis
    2487-2506 9049 UGGAGUACACACCUACCGC 11049 uGGAGuAcAcAccuAccGcdTsdT sense
    2487-2506 9050 GCGGUAGGUGUGUACUCCA 11050 GCGGuAGGUGUGuACUCcAdTsdT antis
    1924-1943 9051 CUAUGUUCCGGAGACAGUG 11051 cuAuGuuccGGAGAcAGuGdTsdT sense
    1924-1943 9052 CACUGUCUCCGGAACAUAG 11052 cACUGUCUCCGGAAcAuAGdTsdT antis
    2176-2195 9053 CUGUUCUCGGUACUACAGG 11053 cuGuucucGGuAcuAcAGGdTsdT sense
    2176-2195 9054 CCUGUAGUACCGAGAACAG 11054 CCUGuAGuACCGAGAAcAGdTsdT antis
    2177-2196 9055 UGUUCUCGGUACUACAGGG 11055 uGuucucGGuAcuAcAGGGdTsdT sense
    2177-2196 9056 CCCUGUAGUACCGAGAACA 11056 CCCUGuAGuACCGAGAAcAdTsdT antis
    2502-2521 9057 CCGCCCGGCUAACACCACU 11057 ccGcccGGcuAAcAccAcudTsdT sense
    2502-2521 9058 AGUGGUGUUAGCCGGGCGG 11058 AGUGGUGUuAGCCGGGCGGdTsdT antis
    2499-2518 9059 CUACCGCCCGGCUAACACC 11059 cuAccGcccGGcuAAcAccdTsdT sense
    2499-2518 9060 GGUGUUAGCCGGGCGGUAG 11060 GGUGUuAGCCGGGCGGuAGdTsdT antis
    2223-2242 9061 AUUACACGUCCAGUAUAGA 11061 AuuAcAcGuccAGuAuAGAdTsdT sense
    2223-2242 9062 UCUAUACUGGACGUGUAAU 11062 UCuAuACUGGACGUGuAAUdTsdT antis
    1873-1892 9063 CUACUCGAGUGGUGAGAAG 11063 cuAcucGAGuGGuGAGAAGdTsdT sense
    1873-1892 9064 CUUCUCACCACUCGAGUAG 11064 CUUCUcACcACUCGAGuAGdTsdT antis
    1918-1937 9065 GCUGGACUAUGUUCCGGAG 11065 GcuGGAcuAuGuuccGGAGdTsdT sense
    1918-1937 9066 CUCCGGAACAUAGUCCAGC 11066 CUCCGGAAcAuAGUCcAGCdTsdT antis
    1919-1938 9067 CUGGACUAUGUUCCGGAGA 11067 cuGGAcuAuGuuccGGAGAdTsdT sense
    1919-1938 9068 UCUCCGGAACAUAGUCCAG 11068 UCUCCGGAAcAuAGUCcAGdTsdT antis
    1950-1969 9069 UCGCCAGACACUAUAGUCG 11069 ucGccAGAcAcuAuAGucGdTsdT sense
    1950-1969 9070 CGACUAUAGUGUCUGGCGA 11070 CGACuAuAGUGUCUGGCGAdTsdT antis
    1958-1977 9071 CACUAUAGUCGAGCCAAGC 11071 cAcuAuAGucGAGccAAGcdTsdT sense
    1958-1977 9072 GCUUGGCUCGACUAUAGUG 11072 GCUUGGCUCGACuAuAGUGdTsdT antis
    2222-2241 9073 GAUUACACGUCCAGUAUAG 11073 GAuuAcAcGuccAGuAuAGdTsdT sense
    2222-2241 9074 CUAUACUGGACGUGUAAUC 11074 CuAuACUGGACGUGuAAUCdTsdT antis
    2224-2243 9075 UUACACGUCCAGUAUAGAU 11075 uuAcAcGuccAGuAuAGAudTsdT sense
    2224-2243 9076 AUCUAUACUGGACGUGUAA 11076 AUCuAuACUGGACGUGuAAdTsdT antis
    2440-2459 9077 CCGGCCCCGAACUCCACCA 11077 ccGGccccGAAcuccAccAdTsdT sense
    2440-2459 9078 UGGUGGAGUUCGGGGCCGG 11078 UGGUGGAGUUCGGGGCCGGdTsdT antis
    2493-2512 9079 ACACACCUACCGCCCGGCU 11079 AcAcAccuAccGcccGGcudTsdT sense
    2493-2512 9080 AGCCGGGCGGUAGGUGUGU 11080 AGCCGGGCGGuAGGUGUGUdTsdT antis
    2494-2513 9081 CACACCUACCGCCCGGCUA 11081 cAcAccuAccGcccGGcuAdTsdT sense
    2494-2513 9082 UAGCCGGGCGGUAGGUGUG 11082 uAGCCGGGCGGuAGGUGUGdTsdT antis
    2497-2516 9083 ACCUACCGCCCGGCUAACA 11083 AccuAccGcccGGcuAAcAdTsdT sense
    2497-2516 9084 UGUUAGCCGGGCGGUAGGU 11084 UGUuAGCCGGGCGGuAGGUdTsdT antis
    2498-2517 9085 CCUACCGCCCGGCUAACAC 11085 ccuAccGcccGGcuAAcAcdTsdT sense
    2498-2517 9086 GUGUUAGCCGGGCGGUAGG 11086 GUGUuAGCCGGGCGGuAGGdTsdT antis
    1525-1544 9087 CAUGUCGGGGCGACCGAGA 11087 cAuGucGGGGcGAccGAGAdTsdT sense
    1525-1544 9088 UCUCGGUCGCCCCGACAUG 11088 UCUCGGUCGCCCCGAcAUGdTsdT antis
    1528-1547 9089 GUCGGGGCGACCGAGAACC 11089 GucGGGGcGAccGAGAAccdTsdT sense
    1528-1547 9090 GGUUCUCGGUCGCCCCGAC 11090 GGUUCUCGGUCGCCCCGACdTsdT antis
    1533-1552 9091 GGCGACCGAGAACCACCUC 11091 GGcGAccGAGAAccAccucdTsdT sense
    1533-1552 9092 GAGGUGGUUCUCGGUCGCC 11092 GAGGUGGUUCUCGGUCGCCdTsdT antis
    1793-1812 9093 GACAAGCGAUUUAAGAACC 11093 GAcAAGcGAuuuAAGAAccdTsdT sense
    1793-1812 9094 GGUUCUUAAAUCGCUUGUC 11094 GGUUCUuAAAUCGCUUGUCdTsdT antis
    1797-1816 9095 AGCGAUUUAAGAACCGAGA 11095 AGcGAuuuAAGAAccGAGAdTsdT sense
    1797-1816 9096 UCUCGGUUCUUAAAUCGCU 11096 UCUCGGUUCUuAAAUCGCUdTsdT antis
    1798-1817 9097 GCGAUUUAAGAACCGAGAG 11097 GcGAuuuAAGAAccGAGAGdTsdT sense
    1798-1817 9098 CUCUCGGUUCUUAAAUCGC 11098 CUCUCGGUUCUuAAAUCGCdTsdT antis
    1799-1818 9099 CGAUUUAAGAACCGAGAGC 11099 cGAuuuAAGAAccGAGAGcdTsdT sense
    1799-1818 9100 GCUCUCGGUUCUUAAAUCG 11100 GCUCUCGGUUCUuAAAUCGdTsdT antis
    1832-1851 9101 AAGCUAGACCACUGUAACA 11101 AAGcuAGAccAcuGuAAcAdTsdT sense
    1832-1851 9102 UGUUACAGUGGUCUAGCUU 11102 UGUuAcAGUGGUCuAGCUUdTsdT antis
    1836-1855 9103 UAGACCACUGUAACAUAGU 11103 uAGAccAcuGuAAcAuAGudTsdT sense
    1836-1855 9104 ACUAUGUUACAGUGGUCUA 11104 ACuAUGUuAcAGUGGUCuAdTsdT antis
    1850-1869 9105 AUAGUCCGACUGCGGUAUU 11105 AuAGuccGAcuGcGGuAuudTsdT sense
    1850-1869 9106 AAUACCGCAGUCGGACUAU 11106 AAuACCGcAGUCGGACuAUdTsdT antis
    1852-1871 9107 AGUCCGACUGCGGUAUUUC 11107 AGuccGAcuGcGGuAuuucdTsdT sense
    1852-1871 9108 GAAAUACCGCAGUCGGACU 11108 GAAAuACCGcAGUCGGACUdTsdT antis
    1853-1872 9109 GUCCGACUGCGGUAUUUCU 11109 GuccGAcuGcGGuAuuucudTsdT sense
    1853-1872 9110 AGAAAUACCGCAGUCGGAC 11110 AGAAAuACCGcAGUCGGACdTsdT antis
    1855-1874 9111 CCGACUGCGGUAUUUCUUC 11111 ccGAcuGcGGuAuuucuucdTsdT sense
    1855-1874 9112 GAAGAAAUACCGCAGUCGG 11112 GAAGAAAuACCGcAGUCGGdTsdT antis
    1870-1889 9113 CUUCUACUCGAGUGGUGAG 11113 cuucuAcucGAGuGGuGAGdTsdT sense
    1870-1889 9114 CUCACCACUCGAGUAGAAG 11114 CUcACcACUCGAGuAGAAGdTsdT antis
    1895-1914 9115 GAUGAGGUCUACCUUAACC 11115 GAuGAGGucuAccuuAAccdTsdT sense
    1895-1914 9116 GGUUAAGGUAGACCUCAUC 11116 GGUuAAGGuAGACCUcAUCdTsdT antis
    1916-1935 9117 GUGCUGGACUAUGUUCCGG 11117 GuGcuGGAcuAuGuuccGGdTsdT sense
    1916-1935 9118 CCGGAACAUAGUCCAGCAC 11118 CCGGAAcAuAGUCcAGcACdTsdT antis
    1927-1946 9119 UGUUCCGGAGACAGUGUAC 11119 uGuuccGGAGAcAGuGuAcdTsdT sense
    1927-1946 9120 GUACACUGUCUCCGGAACA 11120 GuAcACUGUCUCCGGAAcAdTsdT antis
    1953-1972 9121 CCAGACACUAUAGUCGAGC 11121 ccAGAcAcuAuAGucGAGcdTsdT sense
    1953-1972 9122 GCUCGACUAUAGUGUCUGG 11122 GCUCGACuAuAGUGUCUGGdTsdT antis
    1959-1978 9123 ACUAUAGUCGAGCCAAGCA 11123 AcuAuAGucGAGccAAGcAdTsdT sense
    1959-1978 9124 UGCUUGGCUCGACUAUAGU 11124 UGCUUGGCUCGACuAuAGUdTsdT antis
    1960-1979 9125 CUAUAGUCGAGCCAAGCAG 11125 cuAuAGucGAGccAAGcAGdTsdT sense
    1960-1979 9126 CUGCUUGGCUCGACUAUAG 11126 CUGCUUGGCUCGACuAuAGdTsdT antis
    2023-2042 9127 CAGAAGUCUAGCCUAUAUC 11127 cAGAAGucuAGccuAuAucdTsdT sense
    2023-2042 9128 GAUAUAGGCUAGACUUCUG 11128 GAuAuAGGCuAGACUUCUGdTsdT antis
    2089-2108 9129 GUUGGAUCCUGAUACAGCU 11129 GuuGGAuccuGAuAcAGcudTsdT sense
    2089-2108 9130 AGCUGUAUCAGGAUCCAAC 11130 AGCUGuAUcAGGAUCcAACdTsdT antis
    2179-2198 9131 UUCUCGGUACUACAGGGCA 11131 uucucGGuAcuAcAGGGcAdTsdT sense
    2179-2198 9132 UGCCCUGUAGUACCGAGAA 11132 UGCCCUGuAGuACCGAGAAdTsdT antis
    2188-2207 9133 CUACAGGGCACCAGAGUUG 11133 cuAcAGGGcAccAGAGuuGdTsdT sense
    2188-2207 9134 CAACUCUGGUGCCCUGUAG 11134 cAACUCUGGUGCCCUGuAGdTsdT antis
    2218-2237 9135 CACUGAUUACACGUCCAGU 11135 cAcuGAuuAcAcGuccAGudTsdT sense
    2218-2237 9136 ACUGGACGUGUAAUCAGUG 11136 ACUGGACGUGuAAUcAGUGdTsdT antis
    2219-2238 9137 ACUGAUUACACGUCCAGUA 11137 AcuGAuuAcAcGuccAGuAdTsdT sense
    2219-2238 9138 UACUGGACGUGUAAUCAGU 11138 uACUGGACGUGuAAUcAGUdTsdT antis
    2226-2245 9139 ACACGUCCAGUAUAGAUGU 11139 AcAcGuccAGuAuAGAuGudTsdT sense
    2226-2245 9140 ACAUCUAUACUGGACGUGU 11140 AcAUCuAuACUGGACGUGUdTsdT antis
    2227-2246 9141 CACGUCCAGUAUAGAUGUA 11141 cAcGuccAGuAuAGAuGuAdTsdT sense
    2227-2246 9142 UACAUCUAUACUGGACGUG 11142 uAcAUCuAuACUGGACGUGdTsdT antis
    2276-2295 9143 UUGCUAGGACAACCAAUAU 11143 uuGcuAGGAcAAccAAuAudTsdT sense
    2276-2295 9144 AUAUUGGUUGUCCUAGCAA 11144 AuAUUGGUUGUCCuAGcAAdTsdT antis
    2277-2296 9145 UGCUAGGACAACCAAUAUU 11145 uGcuAGGAcAAccAAuAuudTsdT sense
    2277-2296 9146 AAUAUUGGUUGUCCUAGCA 11146 AAuAUUGGUUGUCCuAGcAdTsdT antis
    2279-2298 9147 CUAGGACAACCAAUAUUUC 11147 cuAGGAcAAccAAuAuuucdTsdT sense
    2279-2298 9148 GAAAUAUUGGUUGUCCUAG 11148 GAAAuAUUGGUUGUCCuAGdTsdT antis
    2306-2325 9149 AGUGGUGUGGAUCAGUUGG 11149 AGuGGuGuGGAucAGuuGGdTsdT sense
    2306-2325 9150 CCAACUGAUCCACACCACU 11150 CcAACUGAUCcAcACcACUdTsdT antis
    2488-2507 9151 GGAGUACACACCUACCGCC 11151 GGAGuAcAcAccuAccGccdTsdT sense
    2488-2507 9152 GGCGGUAGGUGUGUACUCC 11152 GGCGGuAGGUGUGuACUCCdTsdT antis
    2491-2510 9153 GUACACACCUACCGCCCGG 11153 GuAcAcAccuAccGcccGGdTsdT sense
    2491-2510 9154 CCGGGCGGUAGGUGUGUAC 11154 CCGGGCGGuAGGUGUGuACdTsdT antis
    2501-2520 9155 ACCGCCCGGCUAACACCAC 11155 AccGcccGGcuAAcAccAcdTsdT sense
    2501-2520 9156 GUGGUGUUAGCCGGGCGGU 11156 GUGGUGUuAGCCGGGCGGUdTsdT antis
    2506-2525 9157 CCGGCUAACACCACUGGAA 11157 ccGGcuAAcAccAcuGGAAdTsdT sense
    2506-2525 9158 UUCCAGUGGUGUUAGCCGG 11158 UUCcAGUGGUGUuAGCCGGdTsdT antis
    1695-1714 9159 CAGACACGAAAGUGAUUGG 11159 cAGAcAcGAAAGuGAuuGGdTsdT sense
    1695-1714 9160 CCAAUCACUUUCGUGUCUG 11160 CcAAUcACUUUCGUGUCUGdTsdT antis
    1720-1739 9161 AUCAUUUGGUGUGGUAUAU 11161 AucAuuuGGuGuGGuAuAudTsdT sense
    1720-1739 9162 AUAUACCACACCAAAUGAU 11162 AuAuACcAcACcAAAUGAUdTsdT antis
    1722-1741 9163 CAUUUGGUGUGGUAUAUCA 11163 cAuuuGGuGuGGuAuAucAdTsdT sense
    1722-1741 9164 UGAUAUACCACACCAAAUG 11164 UGAuAuACcAcACcAAAUGdTsdT antis
    1833-1852 9165 AGCUAGACCACUGUAACAU 11165 AGcuAGAccAcuGuAAcAudTsdT sense
    1833-1852 9166 AUGUUACAGUGGUCUAGCU 11166 AUGUuAcAGUGGUCuAGCUdTsdT antis
    1848-1867 9167 ACAUAGUCCGACUGCGGUA 11167 AcAuAGuccGAcuGcGGuAdTsdT sense
    1848-1867 9168 UACCGCAGUCGGACUAUGU 11168 uACCGcAGUCGGACuAUGUdTsdT antis
    1872-1891 9169 UCUACUCGAGUGGUGAGAA 11169 ucuAcucGAGuGGuGAGAAdTsdT sense
    1872-1891 9170 UUCUCACCACUCGAGUAGA 11170 UUCUcACcACUCGAGuAGAdTsdT antis
    1998-2017 9171 UCAAGUUGUAUAUGUAUCA 11171 ucAAGuuGuAuAuGuAucAdTsdT sense
    1998-2017 9172 UGAUACAUAUACAACUUGA 11172 UGAuAcAuAuAcAACUUGAdTsdT antis
    2011-2030 9173 GUAUCAGCUGUUCAGAAGU 11173 GuAucAGcuGuucAGAAGudTsdT sense
    2011-2030 9174 ACUUCUGAACAGCUGAUAC 11174 ACUUCUGAAcAGCUGAuACdTsdT antis
    2054-2073 9175 AUCUGCCAUCGAGACAUUA 11175 AucuGccAucGAGAcAuuAdTsdT sense
    2054-2073 9176 UAAUGUCUCGAUGGCAGAU 11176 uAAUGUCUCGAUGGcAGAUdTsdT antis
    2153-2172 9177 GGAGAGCCCAAUGUUUCAU 11177 GGAGAGcccAAuGuuucAudTsdT sense
    2153-2172 9178 AUGAAACAUUGGGCUCUCC 11178 AUGAAAcAUUGGGCUCUCCdTsdT antis
    2168-2187 9179 UCAUAUAUCUGUUCUCGGU 11179 ucAuAuAucuGuucucGGudTsdT sense
    2168-2187 9180 ACCGAGAACAGAUAUAUGA 11180 ACCGAGAAcAGAuAuAUGAdTsdT antis
    2181-2200 9181 CUCGGUACUACAGGGCACC 11181 cucGGuAcuAcAGGGcAccdTsdT sense
    2181-2200 9182 GGUGCCCUGUAGUACCGAG 11182 GGUGCCCUGuAGuACCGAGdTsdT antis
    2305-2324 9183 CAGUGGUGUGGAUCAGUUG 11183 cAGuGGuGuGGAucAGuuGdTsdT sense
    2305-2324 9184 CAACUGAUCCACACCACUG 11184 cAACUGAUCcAcACcACUGdTsdT antis
    2354-2373 9185 ACAAGGGAGCAAAUUAGAG 11185 AcAAGGGAGcAAAuuAGAGdTsdT sense
    2354-2373 9186 CUCUAAUUUGCUCCCUUGU 11186 CUCuAAUUUGCUCCCUUGUdTsdT antis
    2427-2446 9187 GGACAAAGGUCUUCCGGCC 11187 GGAcAAAGGucuuccGGccdTsdT sense
    2427-2446 9188 GGCCGGAAGACCUUUGUCC 11188 GGCCGGAAGACCUUUGUCCdTsdT antis
    1529-1548 9189 UCGGGGCGACCGAGAACCA 11189 ucGGGGcGAccGAGAAccAdTsdT sense
    1529-1548 9190 UGGUUCUCGGUCGCCCCGA 11190 UGGUUCUCGGUCGCCCCGAdTsdT antis
    1532-1551 9191 GGGCGACCGAGAACCACCU 11191 GGGcGAccGAGAAccAccudTsdT sense
    1532-1551 9192 AGGUGGUUCUCGGUCGCCC 11192 AGGUGGUUCUCGGUCGCCCdTsdT antis
    1541-1560 9193 AGAACCACCUCCUUUGCGG 11193 AGAAccAccuccuuuGcGGdTsdT sense
    1541-1560 9194 CCGCAAAGGAGGUGGUUCU 11194 CCGcAAAGGAGGUGGUUCUdTsdT antis
    1591-1610 9195 UUUUGGUAGCAUGAAAGUU 11195 uuuuGGuAGcAuGAAAGuudTsdT sense
    1591-1610 9196 AACUUUCAUGCUACCAAAA 11196 AACUUUcAUGCuACcAAAAdTsdT antis
    1677-1696 9197 CACAGGAAGUCAGUUAUAC 11197 cAcAGGAAGucAGuuAuAcdTsdT sense
    1677-1696 9198 GUAUAACUGACUUCCUGUG 11198 GuAuAACUGACUUCCUGUGdTsdT antis
    1679-1698 9199 CAGGAAGUCAGUUAUACAG 11199 cAGGAAGucAGuuAuAcAGdTsdT sense
    1679-1698 9200 CUGUAUAACUGACUUCCUG 11200 CUGuAuAACUGACUUCCUGdTsdT antis
    1680-1699 9201 AGGAAGUCAGUUAUACAGA 11201 AGGAAGucAGuuAuAcAGAdTsdT sense
    1680-1699 9202 UCUGUAUAACUGACUUCCU 11202 UCUGuAuAACUGACUUCCUdTsdT antis
    1681-1700 9203 GGAAGUCAGUUAUACAGAC 11203 GGAAGucAGuuAuAcAGAcdTsdT sense
    1681-1700 9204 GUCUGUAUAACUGACUUCC 11204 GUCUGuAuAACUGACUUCCdTsdT antis
    1705-1724 9205 AGUGAUUGGAAAUGGAUCA 11205 AGuGAuuGGAAAuGGAucAdTsdT sense
    1705-1724 9206 UGAUCCAUUUCCAAUCACU 11206 UGAUCcAUUUCcAAUcACUdTsdT antis
    1706-1725 9207 GUGAUUGGAAAUGGAUCAU 11207 GuGAuuGGAAAuGGAucAudTsdT sense
    1706-1725 9208 AUGAUCCAUUUCCAAUCAC 11208 AUGAUCcAUUUCcAAUcACdTsdT antis
    1708-1727 9209 GAUUGGAAAUGGAUCAUUU 11209 GAuuGGAAAuGGAucAuuudTsdT sense
    1708-1727 9210 AAAUGAUCCAUUUCCAAUC 11210 AAAUGAUCcAUUUCcAAUCdTsdT antis
    1724-1743 9211 UUUGGUGUGGUAUAUCAAG 11211 uuuGGuGuGGuAuAucAAGdTsdT sense
    1724-1743 9212 CUUGAUAUACCACACCAAA 11212 CUUGAuAuACcAcACcAAAdTsdT antis
    1725-1744 9213 UUGGUGUGGUAUAUCAAGC 11213 uuGGuGuGGuAuAucAAGcdTsdT sense
    1725-1744 9214 GCUUGAUAUACCACACCAA 11214 GCUUGAuAuACcAcACcAAdTsdT antis
    1727-1746 9215 GGUGUGGUAUAUCAAGCCA 11215 GGuGuGGuAuAucAAGccAdTsdT sense
    1727-1746 9216 UGGCUUGAUAUACCACACC 11216 UGGCUUGAuAuACcAcACCdTsdT antis
    1739-1758 9217 CAAGCCAAACUUUGUGAUU 11217 cAAGccAAAcuuuGuGAuudTsdT sense
    1739-1758 9218 AAUCACAAAGUUUGGCUUG 11218 AAUcAcAAAGUUUGGCUUGdTsdT antis
    1785-1804 9219 UUCUACAGGACAAGCGAUU 11219 uucuAcAGGAcAAGcGAuudTsdT sense
    1785-1804 9220 AAUCGCUUGUCCUGUAGAA 11220 AAUCGCUUGUCCUGuAGAAdTsdT antis
    1828-1847 9221 GAGAAAGCUAGACCACUGU 11221 GAGAAAGcuAGAccAcuGudTsdT sense
    1828-1847 9222 ACAGUGGUCUAGCUUUCUC 11222 AcAGUGGUCuAGCUUUCUCdTsdT antis
    1829-1848 9223 AGAAAGCUAGACCACUGUA 11223 AGAAAGcuAGAccAcuGuAdTsdT sense
    1829-1848 9224 UACAGUGGUCUAGCUUUCU 11224 uAcAGUGGUCuAGCUUUCUdTsdT antis
    1837-1856 9225 AGACCACUGUAACAUAGUC 11225 AGAccAcuGuAAcAuAGucdTsdT sense
    1837-1856 9226 GACUAUGUUACAGUGGUCU 11226 GACuAUGUuAcAGUGGUCUdTsdT antis
    1839-1858 9227 ACCACUGUAACAUAGUCCG 11227 AccAcuGuAAcAuAGuccGdTsdT sense
    1839-1858 9228 CGGACUAUGUUACAGUGGU 11228 CGGACuAUGUuAcAGUGGUdTsdT antis
    1841-1860 9229 CACUGUAACAUAGUCCGAC 11229 cAcuGuAAcAuAGuccGAcdTsdT sense
    1841-1860 9230 GUCGGACUAUGUUACAGUG 11230 GUCGGACuAUGUuAcAGUGdTsdT antis
    1864-1883 9231 GUAUUUCUUCUACUCGAGU 11231 GuAuuucuucuAcucGAGudTsdT sense
    1864-1883 9232 ACUCGAGUAGAAGAAAUAC 11232 ACUCGAGuAGAAGAAAuACdTsdT antis
    1865-1884 9233 UAUUUCUUCUACUCGAGUG 11233 uAuuucuucuAcucGAGuGdTsdT sense
    1865-1884 9234 CACUCGAGUAGAAGAAAUA 11234 cACUCGAGuAGAAGAAAuAdTsdT antis
    1867-1886 9235 UUUCUUCUACUCGAGUGGU 11235 uuucuucuAcucGAGuGGudTsdT sense
    1867-1886 9236 ACCACUCGAGUAGAAGAAA 11236 ACcACUCGAGuAGAAGAAAdTsdT antis
    1874-1893 9237 UACUCGAGUGGUGAGAAGA 11237 uAcucGAGuGGuGAGAAGAdTsdT sense
    1874-1893 9238 UCUUCUCACCACUCGAGUA 11238 UCUUCUcACcACUCGAGuAdTsdT antis
    1894-1913 9239 AGAUGAGGUCUACCUUAAC 11239 AGAuGAGGucuAccuuAAcdTsdT sense
    1894-1913 9240 GUUAAGGUAGACCUCAUCU 11240 GUuAAGGuAGACCUcAUCUdTsdT antis
    1921-1940 9241 GGACUAUGUUCCGGAGACA 11241 GGAcuAuGuuccGGAGAcAdTsdT sense
    1921-1940 9242 UGUCUCCGGAACAUAGUCC 11242 UGUCUCCGGAAcAuAGUCCdTsdT antis
    1954-1973 9243 CAGACACUAUAGUCGAGCC 11243 cAGAcAcuAuAGucGAGccdTsdT sense
    1954-1973 9244 GGCUCGACUAUAGUGUCUG 11244 GGCUCGACuAuAGUGUCUGdTsdT antis
    2006-2025 9245 UAUAUGUAUCAGCUGUUCA 11245 uAuAuGuAucAGcuGuucAdTsdT sense
    2006-2025 9246 UGAACAGCUGAUACAUAUA 11246 UGAAcAGCUGAuAcAuAuAdTsdT antis
    2017-2036 9247 GCUGUUCAGAAGUCUAGCC 11247 GcuGuucAGAAGucuAGccdTsdT sense
    2017-2036 9248 GGCUAGACUUCUGAACAGC 11248 GGCuAGACUUCUGAAcAGCdTsdT antis
    2019-2038 9249 UGUUCAGAAGUCUAGCCUA 11249 uGuucAGAAGucuAGccuAdTsdT sense
    2019-2038 9250 UAGGCUAGACUUCUGAACA 11250 uAGGCuAGACUUCUGAAcAdTsdT antis
    2026-2045 9251 AAGUCUAGCCUAUAUCCAU 11251 AAGucuAGccuAuAuccAudTsdT sense
    2026-2045 9252 AUGGAUAUAGGCUAGACUU 11252 AUGGAuAuAGGCuAGACUUdTsdT antis
    2052-2071 9253 GAAUCUGCCAUCGAGACAU 11253 GAAucuGccAucGAGAcAudTsdT sense
    2052-2071 9254 AUGUCUCGAUGGCAGAUUC 11254 AUGUCUCGAUGGcAGAUUCdTsdT antis
    2072-2091 9255 AAACCACAGAACCUCUUGU 11255 AAAccAcAGAAccucuuGudTsdT sense
    2072-2091 9256 ACAAGAGGUUCUGUGGUUU 11256 AcAAGAGGUUCUGUGGUUUdTsdT antis
    2082-2101 9257 ACCUCUUGUUGGAUCCUGA 11257 AccucuuGuuGGAuccuGAdTsdT sense
    2082-2101 9258 UCAGGAUCCAACAAGAGGU 11258 UcAGGAUCcAAcAAGAGGUdTsdT antis
    2088-2107 9259 UGUUGGAUCCUGAUACAGC 11259 uGuuGGAuccuGAuAcAGcdTsdT sense
    2088-2107 9260 GCUGUAUCAGGAUCCAACA 11260 GCUGuAUcAGGAUCcAAcAdTsdT antis
    2096-2115 9261 CCUGAUACAGCUGUAUUAA 11261 ccuGAuAcAGcuGuAuuAAdTsdT sense
    2096-2115 9262 UUAAUACAGCUGUAUCAGG 11262 UuAAuAcAGCUGuAUcAGGdTsdT antis
    2167-2186 9263 UUCAUAUAUCUGUUCUCGG 11263 uucAuAuAucuGuucucGGdTsdT sense
    2167-2186 9264 CCGAGAACAGAUAUAUGAA 11264 CCGAGAAcAGAuAuAUGAAdTsdT antis
    2192-2211 9265 AGGGCACCAGAGUUGAUCU 11265 AGGGcAccAGAGuuGAucudTsdT sense
    2192-2211 9266 AGAUCAACUCUGGUGCCCU 11266 AGAUcAACUCUGGUGCCCUdTsdT antis
    2213-2232 9267 GGAGCCACUGAUUACACGU 11267 GGAGccAcuGAuuAcAcGudTsdT sense
    2213-2232 9268 ACGUGUAAUCAGUGGCUCC 11268 ACGUGuAAUcAGUGGCUCCdTsdT antis
    2214-2233 9269 GAGCCACUGAUUACACGUC 11269 GAGccAcuGAuuAcAcGucdTsdT sense
    2214-2233 9270 GACGUGUAAUCAGUGGCUC 11270 GACGUGuAAUcAGUGGCUCdTsdT antis
    2225-2244 9271 UACACGUCCAGUAUAGAUG 11271 uAcAcGuccAGuAuAGAuGdTsdT sense
    2225-2244 9272 CAUCUAUACUGGACGUGUA 11272 cAUCuAuACUGGACGUGuAdTsdT antis
    2229-2248 9273 CGUCCAGUAUAGAUGUAUG 11273 cGuccAGuAuAGAuGuAuGdTsdT sense
    2229-2248 9274 CAUACAUCUAUACUGGACG 11274 cAuAcAUCuAuACUGGACGdTsdT antis
    2230-2249 9275 GUCCAGUAUAGAUGUAUGG 11275 GuccAGuAuAGAuGuAuGGdTsdT sense
    2230-2249 9276 CCAUACAUCUAUACUGGAC 11276 CcAuAcAUCuAuACUGGACdTsdT antis
    2233-2252 9277 CAGUAUAGAUGUAUGGUCU 11277 cAGuAuAGAuGuAuGGucudTsdT sense
    2233-2252 9278 AGACCAUACAUCUAUACUG 11278 AGACcAuAcAUCuAuACUGdTsdT antis
    2236-2255 9279 UAUAGAUGUAUGGUCUGCA 11279 uAuAGAuGuAuGGucuGcAdTsdT sense
    2236-2255 9280 UGCAGACCAUACAUCUAUA 11280 UGcAGACcAuAcAUCuAuAdTsdT antis
    2239-2258 9281 AGAUGUAUGGUCUGCAGGC 11281 AGAuGuAuGGucuGcAGGcdTsdT sense
    2239-2258 9282 GCCUGCAGACCAUACAUCU 11282 GCCUGcAGACcAuAcAUCUdTsdT antis
    2268-2287 9283 CUGAAUUGUUGCUAGGACA 11283 cuGAAuuGuuGcuAGGAcAdTsdT sense
    2268-2287 9284 UGUCCUAGCAACAAUUCAG 11284 UGUCCuAGcAAcAAUUcAGdTsdT antis
    2278-2297 9285 GCUAGGACAACCAAUAUUU 11285 GcuAGGAcAAccAAuAuuudTsdT sense
    2278-2297 9286 AAAUAUUGGUUGUCCUAGC 11286 AAAuAUUGGUUGUCCuAGCdTsdT antis
    2286-2305 9287 AACCAAUAUUUCCUGGGGA 11287 AAccAAuAuuuccuGGGGAdTsdT sense
    2286-2305 9288 UCCCCAGGAAAUAUUGGUU 11288 UCCCcAGGAAAuAUUGGUUdTsdT antis
    2339-2358 9289 GUCCUAGGAACACCAACAA 11289 GuccuAGGAAcAccAAcAAdTsdT sense
    2339-2358 9290 UUGUUGGUGUUCCUAGGAC 11290 UUGUUGGUGUUCCuAGGACdTsdT antis
    2340-2359 9291 UCCUAGGAACACCAACAAG 11291 uccuAGGAAcAccAAcAAGdTsdT sense
    2340-2359 9292 CUUGUUGGUGUUCCUAGGA 11292 CUUGUUGGUGUUCCuAGGAdTsdT antis
    2342-2361 9293 CUAGGAACACCAACAAGGG 11293 cuAGGAAcAccAAcAAGGGdTsdT sense
    2342-2361 9294 CCCUUGUUGGUGUUCCUAG 11294 CCCUUGUUGGUGUUCCuAGdTsdT antis
    2344-2363 9295 AGGAACACCAACAAGGGAG 11295 AGGAAcAccAAcAAGGGAGdTsdT sense
    2344-2363 9296 CUCCCUUGUUGGUGUUCCU 11296 CUCCCUUGUUGGUGUUCCUdTsdT antis
    2355-2374 9297 CAAGGGAGCAAAUUAGAGA 11297 cAAGGGAGcAAAuuAGAGAdTsdT sense
    2355-2374 9298 UCUCUAAUUUGCUCCCUUG 11298 UCUCuAAUUUGCUCCCUUGdTsdT antis
    2397-2416 9299 UCAAAUUCCCUCAAAUCAA 11299 ucAAAuucccucAAAucAAdTsdT sense
    2397-2416 9300 UUGAUUUGAGGGAAUUUGA 11300 UUGAUUUGAGGGAAUUUGAdTsdT antis
    2434-2453 9301 GGUCUUCCGGCCCCGAACU 11301 GGucuuccGGccccGAAcudTsdT sense
    2434-2453 9302 AGUUCGGGGCCGGAAGACC 11302 AGUUCGGGGCCGGAAGACCdTsdT antis
    2435-2454 9303 GUCUUCCGGCCCCGAACUC 11303 GucuuccGGccccGAAcucdTsdT sense
    2435-2454 9304 GAGUUCGGGGCCGGAAGAC 11304 GAGUUCGGGGCCGGAAGACdTsdT antis
    2437-2456 9305 CUUCCGGCCCCGAACUCCA 11305 cuuccGGccccGAAcuccAdTsdT sense
    2437-2456 9306 UGGAGUUCGGGGCCGGAAG 11306 UGGAGUUCGGGGCCGGAAGdTsdT antis
    2453-2472 9307 CCACCAGAGGCAAUUGCAC 11307 ccAccAGAGGcAAuuGcAcdTsdT sense
    2453-2472 9308 GUGCAAUUGCCUCUGGUGG 11308 GUGcAAUUGCCUCUGGUGGdTsdT antis
    2467-2486 9309 UGCACUGUGCAGCCGUCUG 11309 uGcAcuGuGcAGccGucuGdTsdT sense
    2467-2486 9310 CAGACGGCUGCACAGUGCA 11310 cAGACGGCUGcAcAGUGcAdTsdT antis
    2486-2505 9311 CUGGAGUACACACCUACCG 11311 cuGGAGuAcAcAccuAccGdTsdT sense
    2486-2505 9312 CGGUAGGUGUGUACUCCAG 11312 CGGuAGGUGUGuACUCcAGdTsdT antis
    2490-2509 9313 AGUACACACCUACCGCCCG 11313 AGuAcAcAccuAccGcccGdTsdT sense
    2490-2509 9314 CGGGCGGUAGGUGUGUACU 11314 CGGGCGGuAGGUGUGuACUdTsdT antis
    2505-2524 9315 CCCGGCUAACACCACUGGA 11315 cccGGcuAAcAccAcuGGAdTsdT sense
    2505-2524 9316 UCCAGUGGUGUUAGCCGGG 11316 UCcAGUGGUGUuAGCCGGGdTsdT antis
    2508-2527 9317 GGCUAACACCACUGGAAGC 11317 GGcuAAcAccAcuGGAAGcdTsdT sense
    2508-2527 9318 GCUUCCAGUGGUGUUAGCC 11318 GCUUCcAGUGGUGUuAGCCdTsdT antis
    1938-1957 9319 CAGUGUACAGAGUCGCCAG 11319 cAGuGuAcAGAGucGccAGdTsdT sense
    1938-1957 9320 CUGGCGACUCUGUACACUG 11320 CUGGCGACUCUGuAcACUGdTsdT antis
    1985-2004 9321 CCUGUGAUCUAUGUCAAGU 11321 ccuGuGAucuAuGucAAGudTsdT sense
    1985-2004 9322 ACUUGACAUAGAUCACAGG 11322 ACUUGAcAuAGAUcAcAGGdTsdT antis
    2164-2183 9323 UGUUUCAUAUAUCUGUUCU 11323 uGuuucAuAuAucuGuucudTsdT sense
    2164-2183 9324 AGAACAGAUAUAUGAAACA 11324 AGAAcAGAuAuAUGAAAcAdTsdT antis
    2263-2282 9325 GUUGGCUGAAUUGUUGCUA 11325 GuuGGcuGAAuuGuuGcuAdTsdT sense
    2263-2282 9326 UAGCAACAAUUCAGCCAAC 11326 uAGcAAcAAUUcAGCcAACdTsdT antis
    2367-2386 9327 UUAGAGAAAUGAACCCAAA 11327 uuAGAGAAAuGAAcccAAAdTsdT sense
    2367-2386 9328 UUUGGGUUCAUUUCUCUAA 11328 UUUGGGUUcAUUUCUCuAAdTsdT antis
    2395-2414 9329 AUUCAAAUUCCCUCAAAUC 11329 AuucAAAuucccucAAAucdTsdT sense
    2395-2414 9330 GAUUUGAGGGAAUUUGAAU 11330 GAUUUGAGGGAAUUUGAAUdTsdT antis
    1624-1643 9331 UGGCAGCAAGGUAACCACA 11331 uGGcAGcAAGGuAAccAcAdTsdT sense
    1624-1643 9332 UGUGGUUACCUUGCUGCCA 11332 UGUGGUuACCUUGCUGCcAdTsdT antis
    1686-1705 9333 UCAGUUAUACAGACACGAA 11333 ucAGuuAuAcAGAcAcGAAdTsdT sense
    1686-1705 9334 UUCGUGUCUGUAUAACUGA 11334 UUCGUGUCUGuAuAACUGAdTsdT antis
    1979-1998 9335 ACACUCCCUGUGAUCUAUG 11335 AcAcucccuGuGAucuAuGdTsdT sense
    1979-1998 9336 CAUAGAUCACAGGGAGUGU 11336 cAuAGAUcAcAGGGAGUGUdTsdT antis
    2080-2099 9337 GAACCUCUUGUUGGAUCCU 11337 GAAccucuuGuuGGAuccudTsdT sense
    2080-2099 9338 AGGAUCCAACAAGAGGUUC 11338 AGGAUCcAAcAAGAGGUUCdTsdT antis
    2091-2110 9339 UGGAUCCUGAUACAGCUGU 11339 uGGAuccuGAuAcAGcuGudTsdT sense
    2091-2110 9340 ACAGCUGUAUCAGGAUCCA 11340 AcAGCUGuAUcAGGAUCcAdTsdT antis
    2162-2181 9341 AAUGUUUCAUAUAUCUGUU 11341 AAuGuuucAuAuAucuGuudTsdT sense
    2162-2181 9342 AACAGAUAUAUGAAACAUU 11342 AAcAGAuAuAUGAAAcAUUdTsdT antis
    2175-2194 9343 UCUGUUCUCGGUACUACAG 11343 ucuGuucucGGuAcuAcAGdTsdT sense
    2175-2194 9344 CUGUAGUACCGAGAACAGA 11344 CUGuAGuACCGAGAAcAGAdTsdT antis
    2267-2286 9345 GCUGAAUUGUUGCUAGGAC 11345 GcuGAAuuGuuGcuAGGAcdTsdT sense
    2267-2286 9346 GUCCUAGCAACAAUUCAGC 11346 GUCCuAGcAAcAAUUcAGCdTsdT antis
    2309-2328 9347 GGUGUGGAUCAGUUGGUGG 11347 GGuGuGGAucAGuuGGuGGdTsdT sense
    2309-2328 9348 CCACCAACUGAUCCACACC 11348 CcACcAACUGAUCcAcACCdTsdT antis
    2451-2470 9349 CUCCACCAGAGGCAAUUGC 11349 cuccAccAGAGGcAAuuGcdTsdT sense
    2451-2470 9350 GCAAUUGCCUCUGGUGGAG 11350 GcAAUUGCCUCUGGUGGAGdTsdT antis
    1546-1565 9351 CACCUCCUUUGCGGAGAGC 11351 cAccuccuuuGcGGAGAGcdTsdT sense
    1546-1565 9352 GCUCUCCGCAAAGGAGGUG 11352 GCUCUCCGcAAAGGAGGUGdTsdT antis
    1936-1955 9353 GACAGUGUACAGAGUCGCC 11353 GAcAGuGuAcAGAGucGccdTsdT sense
    1936-1955 9354 GGCGACUCUGUACACUGUC 11354 GGCGACUCUGuAcACUGUCdTsdT antis
    1592-1611 9355 UUUGGUAGCAUGAAAGUUA 11355 uuuGGuAGcAuGAAAGuuAdTsdT sense
    1592-1611 9356 UAACUUUCAUGCUACCAAA 11356 uAACUUUcAUGCuACcAAAdTsdT antis
    1620-1639 9357 AAGAUGGCAGCAAGGUAAC 11357 AAGAuGGcAGcAAGGuAAcdTsdT sense
    1620-1639 9358 GUUACCUUGCUGCCAUCUU 11358 GUuACCUUGCUGCcAUCUUdTsdT antis
    1675-1694 9359 GCCACAGGAAGUCAGUUAU 11359 GccAcAGGAAGucAGuuAudTsdT sense
    1675-1694 9360 AUAACUGACUUCCUGUGGC 11360 AuAACUGACUUCCUGUGGCdTsdT antis
    1723-1742 9361 AUUUGGUGUGGUAUAUCAA 11361 AuuuGGuGuGGuAuAucAAdTsdT sense
    1723-1742 9362 UUGAUAUACCACACCAAAU 11362 UUGAuAuACcAcACcAAAUdTsdT antis
    1738-1757 9363 UCAAGCCAAACUUUGUGAU 11363 ucAAGccAAAcuuuGuGAudTsdT sense
    1738-1757 9364 AUCACAAAGUUUGGCUUGA 11364 AUcAcAAAGUUUGGCUUGAdTsdT antis
    1758-1777 9365 CUGGAGAACUGGUUGCCAU 11365 cuGGAGAAcuGGuuGccAudTsdT sense
    1758-1777 9366 AUGGCAACCAGUUCUCCAG 11366 AUGGcAACcAGUUCUCcAGdTsdT antis
    2027-2046 9367 AGUCUAGCCUAUAUCCAUU 11367 AGucuAGccuAuAuccAuudTsdT sense
    2027-2046 9368 AAUGGAUAUAGGCUAGACU 11368 AAUGGAuAuAGGCuAGACUdTsdT antis
    2083-2102 9369 CCUCUUGUUGGAUCCUGAU 11369 ccucuuGuuGGAuccuGAudTsdT sense
    2083-2102 9370 AUCAGGAUCCAACAAGAGG 11370 AUcAGGAUCcAAcAAGAGGdTsdT antis
    2097-2116 9371 CUGAUACAGCUGUAUUAAA 11371 cuGAuAcAGcuGuAuuAAAdTsdT sense
    2097-2116 9372 UUUAAUACAGCUGUAUCAG 11372 UUuAAuAcAGCUGuAUcAGdTsdT antis
    2104-2123 9373 AGCUGUAUUAAAACUCUGU 11373 AGcuGuAuuAAAAcucuGudTsdT sense
    2104-2123 9374 ACAGAGUUUUAAUACAGCU 11374 AcAGAGUUUuAAuAcAGCUdTsdT antis
    2208-2227 9375 UCUUUGGAGCCACUGAUUA 11375 ucuuuGGAGccAcuGAuuAdTsdT sense
    2208-2227 9376 UAAUCAGUGGCUCCAAAGA 11376 uAAUcAGUGGCUCcAAAGAdTsdT antis
    2210-2229 9377 UUUGGAGCCACUGAUUACA 11377 uuuGGAGccAcuGAuuAcAdTsdT sense
    2210-2229 9378 UGUAAUCAGUGGCUCCAAA 11378 UGuAAUcAGUGGCUCcAAAdTsdT antis
    2304-2323 9379 ACAGUGGUGUGGAUCAGUU 11379 AcAGuGGuGuGGAucAGuudTsdT sense
    2304-2323 9380 AACUGAUCCACACCACUGU 11380 AACUGAUCcAcACcACUGUdTsdT antis
    2328-2347 9381 AAAUAAUAAAGGUCCUAGG 11381 AAAuAAuAAAGGuccuAGGdTsdT sense
    2328-2347 9382 CCUAGGACCUUUAUUAUUU 11382 CCuAGGACCUUuAUuAUUUdTsdT antis
    2390-2409 9383 ACAGAAUUCAAAUUCCCUC 11383 AcAGAAuucAAAuucccucdTsdT sense
    2390-2409 9384 GAGGGAAUUUGAAUUCUGU 11384 GAGGGAAUUUGAAUUCUGUdTsdT antis
    2018-2037 9385 CUGUUCAGAAGUCUAGCCU 11385 cuGuucAGAAGucuAGccudTsdT sense
    2018-2037 9386 AGGCUAGACUUCUGAACAG 11386 AGGCuAGACUUCUGAAcAGdTsdT antis
    2338-2357 9387 GGUCCUAGGAACACCAACA 11387 GGuccuAGGAAcAccAAcAdTsdT sense
    2338-2357 9388 UGUUGGUGUUCCUAGGACC 11388 UGUUGGUGUUCCuAGGACCdTsdT antis
    2351-2370 9389 CCAACAAGGGAGCAAAUUA 11389 ccAAcAAGGGAGcAAAuuAdTsdT sense
    2351-2370 9390 UAAUUUGCUCCCUUGUUGG 11390 uAAUUUGCUCCCUUGUUGGdTsdT antis
    2433-2452 9391 AGGUCUUCCGGCCCCGAAC 11391 AGGucuuccGGccccGAAcdTsdT sense
    2433-2452 9392 GUUCGGGGCCGGAAGACCU 11392 GUUCGGGGCCGGAAGACCUdTsdT antis
    2180-2199 9393 UCUCGGUACUACAGGGCAC 11393 ucucGGuAcuAcAGGGcAcdTsdT sense
    2180-2199 9394 GUGCCCUGUAGUACCGAGA 11394 GUGCCCUGuAGuACCGAGAdTsdT antis
    1644-1663 9395 UAGUGGCAACUCCUGGCCA 11395 uAGuGGcAAcuccuGGccAdTsdT sense
    1644-1663 9396 UGGCCAGGAGUUGCCACUA 11396 UGGCcAGGAGUUGCcACuAdTsdT antis
    1827-1846 9397 UGAGAAAGCUAGACCACUG 11397 uGAGAAAGcuAGAccAcuGdTsdT sense
    1827-1846 9398 CAGUGGUCUAGCUUUCUCA 11398 cAGUGGUCuAGCUUUCUcAdTsdT antis
    2098-2117 9399 UGAUACAGCUGUAUUAAAA 11399 uGAuAcAGcuGuAuuAAAAdTsdT sense
    2098-2117 9400 UUUUAAUACAGCUGUAUCA 11400 UUUuAAuAcAGCUGuAUcAdTsdT antis
    2254-2273 9401 AGGCUGUGUGUUGGCUGAA 11401 AGGcuGuGuGuuGGcuGAAdTsdT sense
    2254-2273 9402 UUCAGCCAACACACAGCCU 11402 UUcAGCcAAcAcAcAGCCUdTsdT antis
    1674-1693 9403 GGCCACAGGAAGUCAGUUA 11403 GGccAcAGGAAGucAGuuAdTsdT sense
    1674-1693 9404 UAACUGACUUCCUGUGGCC 11404 uAACUGACUUCCUGUGGCCdTsdT antis
    2495-2514 9405 ACACCUACCGCCCGGCUAA 11405 AcAccuAccGcccGGcuAAdTsdT sense
    2495-2514 9406 UUAGCCGGGCGGUAGGUGU 11406 UuAGCCGGGCGGuAGGUGUdTsdT antis
    1794-1813 9407 ACAAGCGAUUUAAGAACCG 11407 AcAAGcGAuuuAAGAAccGdTsdT sense
    1794-1813 9408 CGGUUCUUAAAUCGCUUGU 11408 CGGUUCUuAAAUCGCUUGUdTsdT antis
    1861-1880 9409 GCGGUAUUUCUUCUACUCG 11409 GcGGuAuuucuucuAcucGdTsdT sense
    1861-1880 9410 CGAGUAGAAGAAAUACCGC 11410 CGAGuAGAAGAAAuACCGCdTsdT antis
    1989-2008 9411 UGAUCUAUGUCAAGUUGUA 11411 uGAucuAuGucAAGuuGuAdTsdT sense
    1989-2008 9412 UACAACUUGACAUAGAUCA 11412 uAcAACUUGAcAuAGAUcAdTsdT antis
    2025-2044 9413 GAAGUCUAGCCUAUAUCCA 11413 GAAGucuAGccuAuAuccAdTsdT sense
    2025-2044 9414 UGGAUAUAGGCUAGACUUC 11414 UGGAuAuAGGCuAGACUUCdTsdT antis
    2028-2047 9415 GUCUAGCCUAUAUCCAUUC 11415 GucuAGccuAuAuccAuucdTsdT sense
    2028-2047 9416 GAAUGGAUAUAGGCUAGAC 11416 GAAUGGAuAuAGGCuAGACdTsdT antis
    2029-2048 9417 UCUAGCCUAUAUCCAUUCC 11417 ucuAGccuAuAuccAuuccdTsdT sense
    2029-2048 9418 GGAAUGGAUAUAGGCUAGA 11418 GGAAUGGAuAuAGGCuAGAdTsdT antis
    2275-2294 9419 GUUGCUAGGACAACCAAUA 11419 GuuGcuAGGAcAAccAAuAdTsdT sense
    2275-2294 9420 UAUUGGUUGUCCUAGCAAC 11420 uAUUGGUUGUCCuAGcAACdTsdT antis
    1593-1612 9421 UUGGUAGCAUGAAAGUUAG 11421 uuGGuAGcAuGAAAGuuAGdTsdT sense
    1593-1612 9422 CUAACUUUCAUGCUACCAA 11422 CuAACUUUcAUGCuACcAAdTsdT antis
    1690-1709 9423 UUAUACAGACACGAAAGUG 11423 uuAuAcAGAcAcGAAAGuGdTsdT sense
    1690-1709 9424 CACUUUCGUGUCUGUAUAA 11424 cACUUUCGUGUCUGuAuAAdTsdT antis
    1795-1814 9425 CAAGCGAUUUAAGAACCGA 11425 cAAGcGAuuuAAGAAccGAdTsdT sense
    1795-1814 9426 UCGGUUCUUAAAUCGCUUG 11426 UCGGUUCUuAAAUCGCUUGdTsdT antis
    1822-1841 9427 GAUCAUGAGAAAGCUAGAC 11427 GAucAuGAGAAAGcuAGAcdTsdT sense
    1822-1841 9428 GUCUAGCUUUCUCAUGAUC 11428 GUCuAGCUUUCUcAUGAUCdTsdT antis
    1901-1920 9429 GUCUACCUUAACCUGGUGC 11429 GucuAccuuAAccuGGuGcdTsdT sense
    1901-1920 9430 GCACCAGGUUAAGGUAGAC 11430 GcACcAGGUuAAGGuAGACdTsdT antis
    1926-1945 9431 AUGUUCCGGAGACAGUGUA 11431 AuGuuccGGAGAcAGuGuAdTsdT sense
    1926-1945 9432 UACACUGUCUCCGGAACAU 11432 uAcACUGUCUCCGGAAcAUdTsdT antis
    1947-1966 9433 GAGUCGCCAGACACUAUAG 11433 GAGucGccAGAcAcuAuAGdTsdT sense
    1947-1966 9434 CUAUAGUGUCUGGCGACUC 11434 CuAuAGUGUCUGGCGACUCdTsdT antis
    1949-1968 9435 GUCGCCAGACACUAUAGUC 11435 GucGccAGAcAcuAuAGucdTsdT sense
    1949-1968 9436 GACUAUAGUGUCUGGCGAC 11436 GACuAuAGUGUCUGGCGACdTsdT antis
    1956-1975 9437 GACACUAUAGUCGAGCCAA 11437 GAcAcuAuAGucGAGccAAdTsdT sense
    1956-1975 9438 UUGGCUCGACUAUAGUGUC 11438 UUGGCUCGACuAuAGUGUCdTsdT antis
    1977-1996 9439 AGACACUCCCUGUGAUCUA 11439 AGAcAcucccuGuGAucuAdTsdT sense
    1977-1996 9440 UAGAUCACAGGGAGUGUCU 11440 uAGAUcAcAGGGAGUGUCUdTsdT antis
    1990-2009 9441 GAUCUAUGUCAAGUUGUAU 11441 GAucuAuGucAAGuuGuAudTsdT sense
    1990-2009 9442 AUACAACUUGACAUAGAUC 11442 AuAcAACUUGAcAuAGAUCdTsdT antis
    2008-2027 9443 UAUGUAUCAGCUGUUCAGA 11443 uAuGuAucAGcuGuucAGAdTsdT sense
    2008-2027 9444 UCUGAACAGCUGAUACAUA 11444 UCUGAAcAGCUGAuAcAuAdTsdT antis
    2047-2066 9445 CUUUGGAAUCUGCCAUCGA 11445 cuuuGGAAucuGccAucGAdTsdT sense
    2047-2066 9446 UCGAUGGCAGAUUCCAAAG 11446 UCGAUGGcAGAUUCcAAAGdTsdT antis
    2187-2206 9447 ACUACAGGGCACCAGAGUU 11447 AcuAcAGGGcAccAGAGuudTsdT sense
    2187-2206 9448 AACUCUGGUGCCCUGUAGU 11448 AACUCUGGUGCCCUGuAGUdTsdT antis
    2307-2326 9449 GUGGUGUGGAUCAGUUGGU 11449 GuGGuGuGGAucAGuuGGudTsdT sense
    2307-2326 9450 ACCAACUGAUCCACACCAC 11450 ACcAACUGAUCcAcACcACdTsdT antis
    2357-2376 9451 AGGGAGCAAAUUAGAGAAA 11451 AGGGAGcAAAuuAGAGAAAdTsdT sense
    2357-2376 9452 UUUCUCUAAUUUGCUCCCU 11452 UUUCUCuAAUUUGCUCCCUdTsdT antis
    2405-2424 9453 CCUCAAAUCAAGGCACAUC 11453 ccucAAAucAAGGcAcAucdTsdT sense
    2405-2424 9454 GAUGUGCCUUGAUUUGAGG 11454 GAUGUGCCUUGAUUUGAGGdTsdT antis
    2483-2502 9455 CUGCUGGAGUACACACCUA 11455 cuGcuGGAGuAcAcAccuAdTsdT sense
    2483-2502 9456 UAGGUGUGUACUCCAGCAG 11456 uAGGUGUGuACUCcAGcAGdTsdT antis
    1629-1648 9457 GCAAGGUAACCACAGUAGU 11457 GcAAGGuAAccAcAGuAGudTsdT sense
    1629-1648 9458 ACUACUGUGGUUACCUUGC 11458 ACuACUGUGGUuACCUUGCdTsdT antis
    1972-1991 9459 CAAGCAGACACUCCCUGUG 11459 cAAGcAGAcAcucccuGuGdTsdT sense
    1972-1991 9460 CACAGGGAGUGUCUGCUUG 11460 cAcAGGGAGUGUCUGCUUGdTsdT antis
    1622-1641 9461 GAUGGCAGCAAGGUAACCA 11461 GAuGGcAGcAAGGuAAccAdTsdT sense
    1622-1641 9462 UGGUUACCUUGCUGCCAUC 11462 UGGUuACCUUGCUGCcAUCdTsdT antis
    1635-1654 9463 UAACCACAGUAGUGGCAAC 11463 uAAccAcAGuAGuGGcAAcdTsdT sense
    1635-1654 9464 GUUGCCACUACUGUGGUUA 11464 GUUGCcACuACUGUGGUuAdTsdT antis
    1790-1809 9465 CAGGACAAGCGAUUUAAGA 11465 cAGGAcAAGcGAuuuAAGAdTsdT sense
    1790-1809 9466 UCUUAAAUCGCUUGUCCUG 11466 UCUuAAAUCGCUUGUCCUGdTsdT antis
    1818-1837 9467 UCCAGAUCAUGAGAAAGCU 11467 uccAGAucAuGAGAAAGcudTsdT sense
    1818-1837 9468 AGCUUUCUCAUGAUCUGGA 11468 AGCUUUCUcAUGAUCUGGAdTsdT antis
    1854-1873 9469 UCCGACUGCGGUAUUUCUU 11469 uccGAcuGcGGuAuuucuudTsdT sense
    1854-1873 9470 AAGAAAUACCGCAGUCGGA 11470 AAGAAAuACCGcAGUCGGAdTsdT antis
    1942-1961 9471 GUACAGAGUCGCCAGACAC 11471 GuAcAGAGucGccAGAcAcdTsdT sense
    1942-1961 9472 GUGUCUGGCGACUCUGUAC 11472 GUGUCUGGCGACUCUGuACdTsdT antis
    1988-2007 9473 GUGAUCUAUGUCAAGUUGU 11473 GuGAucuAuGucAAGuuGudTsdT sense
    1988-2007 9474 ACAACUUGACAUAGAUCAC 11474 AcAACUUGAcAuAGAUcACdTsdT antis
    2055-2074 9475 UCUGCCAUCGAGACAUUAA 11475 ucuGccAucGAGAcAuuAAdTsdT sense
    2055-2074 9476 UUAAUGUCUCGAUGGCAGA 11476 UuAAUGUCUCGAUGGcAGAdTsdT antis
    2217-2236 9477 CCACUGAUUACACGUCCAG 11477 ccAcuGAuuAcAcGuccAGdTsdT sense
    2217-2236 9478 CUGGACGUGUAAUCAGUGG 11478 CUGGACGUGuAAUcAGUGGdTsdT antis
    2235-2254 9479 GUAUAGAUGUAUGGUCUGC 11479 GuAuAGAuGuAuGGucuGcdTsdT sense
    2235-2254 9480 GCAGACCAUACAUCUAUAC 11480 GcAGACcAuAcAUCuAuACdTsdT antis
    2258-2277 9481 UGUGUGUUGGCUGAAUUGU 11481 uGuGuGuuGGcuGAAuuGudTsdT sense
    2258-2277 9482 ACAAUUCAGCCAACACACA 11482 AcAAUUcAGCcAAcAcAcAdTsdT antis
    2269-2288 9483 UGAAUUGUUGCUAGGACAA 11483 uGAAuuGuuGcuAGGAcAAdTsdT sense
    2269-2288 9484 UUGUCCUAGCAACAAUUCA 11484 UUGUCCuAGcAAcAAUUcAdTsdT antis
    2404-2423 9485 CCCUCAAAUCAAGGCACAU 11485 cccucAAAucAAGGcAcAudTsdT sense
    2404-2423 9486 AUGUGCCUUGAUUUGAGGG 11486 AUGUGCCUUGAUUUGAGGGdTsdT antis
    2423-2442 9487 CCUUGGACAAAGGUCUUCC 11487 ccuuGGAcAAAGGucuuccdTsdT sense
    2423-2442 9488 GGAAGACCUUUGUCCAAGG 11488 GGAAGACCUUUGUCcAAGGdTsdT antis
    2455-2474 9489 ACCAGAGGCAAUUGCACUG 11489 AccAGAGGcAAuuGcAcuGdTsdT sense
    2455-2474 9490 CAGUGCAAUUGCCUCUGGU 11490 cAGUGcAAUUGCCUCUGGUdTsdT antis
    1586-1605 9491 UCAGCUUUUGGUAGCAUGA 11491 ucAGcuuuuGGuAGcAuGAdTsdT sense
    1586-1605 9492 UCAUGCUACCAAAAGCUGA 11492 UcAUGCuACcAAAAGCUGAdTsdT antis
    1601-1620 9493 AUGAAAGUUAGCAGAGAUA 11493 AuGAAAGuuAGcAGAGAuAdTsdT sense
    1601-1620 9494 UAUCUCUGCUAACUUUCAU 11494 uAUCUCUGCuAACUUUcAUdTsdT antis
    1621-1640 9495 AGAUGGCAGCAAGGUAACC 11495 AGAuGGcAGcAAGGuAAccdTsdT sense
    1621-1640 9496 GGUUACCUUGCUGCCAUCU 11496 GGUuACCUUGCUGCcAUCUdTsdT antis
    1626-1645 9497 GCAGCAAGGUAACCACAGU 11497 GcAGcAAGGuAAccAcAGudTsdT sense
    1626-1645 9498 ACUGUGGUUACCUUGCUGC 11498 ACUGUGGUuACCUUGCUGCdTsdT antis
    1658-1677 9499 GGCCAGGGUCCUGACAGGC 11499 GGccAGGGuccuGAcAGGcdTsdT sense
    1658-1677 9500 GCCUGUCAGGACCCUGGCC 11500 GCCUGUcAGGACCCUGGCCdTsdT antis
    1683-1702 9501 AAGUCAGUUAUACAGACAC 11501 AAGucAGuuAuAcAGAcAcdTsdT sense
    1683-1702 9502 GUGUCUGUAUAACUGACUU 11502 GUGUCUGuAuAACUGACUUdTsdT antis
    1709-1728 9503 AUUGGAAAUGGAUCAUUUG 11503 AuuGGAAAuGGAucAuuuGdTsdT sense
    1709-1728 9504 CAAAUGAUCCAUUUCCAAU 11504 cAAAUGAUCcAUUUCcAAUdTsdT antis
    1710-1729 9505 UUGGAAAUGGAUCAUUUGG 11505 uuGGAAAuGGAucAuuuGGdTsdT sense
    1710-1729 9506 CCAAAUGAUCCAUUUCCAA 11506 CcAAAUGAUCcAUUUCcAAdTsdT antis
    1726-1745 9507 UGGUGUGGUAUAUCAAGCC 11507 uGGuGuGGuAuAucAAGccdTsdT sense
    1726-1745 9508 GGCUUGAUAUACCACACCA 11508 GGCUUGAuAuACcAcACcAdTsdT antis
    1740-1759 9509 AAGCCAAACUUUGUGAUUC 11509 AAGccAAAcuuuGuGAuucdTsdT sense
    1740-1759 9510 GAAUCACAAAGUUUGGCUU 11510 GAAUcAcAAAGUUUGGCUUdTsdT antis
    1754-1773 9511 GAUUCUGGAGAACUGGUUG 11511 GAuucuGGAGAAcuGGuuGdTsdT sense
    1754-1773 9512 CAACCAGUUCUCCAGAAUC 11512 cAACcAGUUCUCcAGAAUCdTsdT antis
    1755-1774 9513 AUUCUGGAGAACUGGUUGC 11513 AuucuGGAGAAcuGGuuGcdTsdT sense
    1755-1774 9514 GCAACCAGUUCUCCAGAAU 11514 GcAACcAGUUCUCcAGAAUdTsdT antis
    1757-1776 9515 UCUGGAGAACUGGUUGCCA 11515 ucuGGAGAAcuGGuuGccAdTsdT sense
    1757-1776 9516 UGGCAACCAGUUCUCCAGA 11516 UGGcAACcAGUUCUCcAGAdTsdT antis
    1786-1805 9517 UCUACAGGACAAGCGAUUU 11517 ucuAcAGGAcAAGcGAuuudTsdT sense
    1786-1805 9518 AAAUCGCUUGUCCUGUAGA 11518 AAAUCGCUUGUCCUGuAGAdTsdT antis
    1834-1853 9519 GCUAGACCACUGUAACAUA 11519 GcuAGAccAcuGuAAcAuAdTsdT sense
    1834-1853 9520 UAUGUUACAGUGGUCUAGC 11520 uAUGUuAcAGUGGUCuAGCdTsdT antis
    1886-1905 9521 GAGAAGAAAGAUGAGGUCU 11521 GAGAAGAAAGAuGAGGucudTsdT sense
    1886-1905 9522 AGACCUCAUCUUUCUUCUC 11522 AGACCUcAUCUUUCUUCUCdTsdT antis
    1887-1906 9523 AGAAGAAAGAUGAGGUCUA 11523 AGAAGAAAGAuGAGGucuAdTsdT sense
    1887-1906 9524 UAGACCUCAUCUUUCUUCU 11524 uAGACCUcAUCUUUCUUCUdTsdT antis
    1892-1911 9525 AAAGAUGAGGUCUACCUUA 11525 AAAGAuGAGGucuAccuuAdTsdT sense
    1892-1911 9526 UAAGGUAGACCUCAUCUUU 11526 uAAGGuAGACCUcAUCUUUdTsdT antis
    1893-1912 9527 AAGAUGAGGUCUACCUUAA 11527 AAGAuGAGGucuAccuuAAdTsdT sense
    1893-1912 9528 UUAAGGUAGACCUCAUCUU 11528 UuAAGGuAGACCUcAUCUUdTsdT antis
    1925-1944 9529 UAUGUUCCGGAGACAGUGU 11529 uAuGuuccGGAGAcAGuGudTsdT sense
    1925-1944 9530 ACACUGUCUCCGGAACAUA 11530 AcACUGUCUCCGGAAcAuAdTsdT antis
    1937-1956 9531 ACAGUGUACAGAGUCGCCA 11531 AcAGuGuAcAGAGucGccAdTsdT sense
    1937-1956 9532 UGGCGACUCUGUACACUGU 11532 UGGCGACUCUGuAcACUGUdTsdT antis
    1978-1997 9533 GACACUCCCUGUGAUCUAU 11533 GAcAcucccuGuGAucuAudTsdT sense
    1978-1997 9534 AUAGAUCACAGGGAGUGUC 11534 AuAGAUcAcAGGGAGUGUCdTsdT antis
    1980-1999 9535 CACUCCCUGUGAUCUAUGU 11535 cAcucccuGuGAucuAuGudTsdT sense
    1980-1999 9536 ACAUAGAUCACAGGGAGUG 11536 AcAuAGAUcAcAGGGAGUGdTsdT antis
    2005-2024 9537 GUAUAUGUAUCAGCUGUUC 11537 GuAuAuGuAucAGcuGuucdTsdT sense
    2005-2024 9538 GAACAGCUGAUACAUAUAC 11538 GAAcAGCUGAuAcAuAuACdTsdT antis
    2074-2093 9539 ACCACAGAACCUCUUGUUG 11539 AccAcAGAAccucuuGuuGdTsdT sense
    2074-2093 9540 CAACAAGAGGUUCUGUGGU 11540 cAAcAAGAGGUUCUGUGGUdTsdT antis
    2081-2100 9541 AACCUCUUGUUGGAUCCUG 11541 AAccucuuGuuGGAuccuGdTsdT sense
    2081-2100 9542 CAGGAUCCAACAAGAGGUU 11542 cAGGAUCcAAcAAGAGGUUdTsdT antis
    2094-2113 9543 AUCCUGAUACAGCUGUAUU 11543 AuccuGAuAcAGcuGuAuudTsdT sense
    2094-2113 9544 AAUACAGCUGUAUCAGGAU 11544 AAuAcAGCUGuAUcAGGAUdTsdT antis
    2101-2120 9545 UACAGCUGUAUUAAAACUC 11545 uAcAGcuGuAuuAAAAcucdTsdT sense
    2101-2120 9546 GAGUUUUAAUACAGCUGUA 11546 GAGUUUuAAuAcAGCUGuAdTsdT antis
    2138-2157 9547 AAGCAGCUGGUCCGAGGAG 11547 AAGcAGcuGGuccGAGGAGdTsdT sense
    2138-2157 9548 CUCCUCGGACCAGCUGCUU 11548 CUCCUCGGACcAGCUGCUUdTsdT antis
    2161-2180 9549 CAAUGUUUCAUAUAUCUGU 11549 cAAuGuuucAuAuAucuGudTsdT sense
    2161-2180 9550 ACAGAUAUAUGAAACAUUG 11550 AcAGAuAuAUGAAAcAUUGdTsdT antis
    2171-2190 9551 UAUAUCUGUUCUCGGUACU 11551 uAuAucuGuucucGGuAcudTsdT sense
    2171-2190 9552 AGUACCGAGAACAGAUAUA 11552 AGuACCGAGAAcAGAuAuAdTsdT antis
    2178-2197 9553 GUUCUCGGUACUACAGGGC 11553 GuucucGGuAcuAcAGGGcdTsdT sense
    2178-2197 9554 GCCCUGUAGUACCGAGAAC 11554 GCCCUGuAGuACCGAGAACdTsdT antis
    2193-2212 9555 GGGCACCAGAGUUGAUCUU 11555 GGGcAccAGAGuuGAucuudTsdT sense
    2193-2212 9556 AAGAUCAACUCUGGUGCCC 11556 AAGAUcAACUCUGGUGCCCdTsdT antis
    2197-2216 9557 ACCAGAGUUGAUCUUUGGA 11557 AccAGAGuuGAucuuuGGAdTsdT sense
    2197-2216 9558 UCCAAAGAUCAACUCUGGU 11558 UCcAAAGAUcAACUCUGGUdTsdT antis
    2209-2228 9559 CUUUGGAGCCACUGAUUAC 11559 cuuuGGAGccAcuGAuuAcdTsdT sense
    2209-2228 9560 GUAAUCAGUGGCUCCAAAG 11560 GuAAUcAGUGGCUCcAAAGdTsdT antis
    2215-2234 9561 AGCCACUGAUUACACGUCC 11561 AGccAcuGAuuAcAcGuccdTsdT sense
    2215-2234 9562 GGACGUGUAAUCAGUGGCU 11562 GGACGUGuAAUcAGUGGCUdTsdT antis
    2231-2250 9563 UCCAGUAUAGAUGUAUGGU 11563 uccAGuAuAGAuGuAuGGudTsdT sense
    2231-2250 9564 ACCAUACAUCUAUACUGGA 11564 ACcAuAcAUCuAuACUGGAdTsdT antis
    2308-2327 9565 UGGUGUGGAUCAGUUGGUG 11565 uGGuGuGGAucAGuuGGuGdTsdT sense
    2308-2327 9566 CACCAACUGAUCCACACCA 11566 cACcAACUGAUCcAcACcAdTsdT antis
    2334-2353 9567 UAAAGGUCCUAGGAACACC 11567 uAAAGGuccuAGGAAcAccdTsdT sense
    2334-2353 9568 GGUGUUCCUAGGACCUUUA 11568 GGUGUUCCuAGGACCUUuAdTsdT antis
    2336-2355 9569 AAGGUCCUAGGAACACCAA 11569 AAGGuccuAGGAAcAccAAdTsdT sense
    2336-2355 9570 UUGGUGUUCCUAGGACCUU 11570 UUGGUGUUCCuAGGACCUUdTsdT antis
    2337-2356 9571 AGGUCCUAGGAACACCAAC 11571 AGGuccuAGGAAcAccAAcdTsdT sense
    2337-2356 9572 GUUGGUGUUCCUAGGACCU 11572 GUUGGUGUUCCuAGGACCUdTsdT antis
    2343-2362 9573 UAGGAACACCAACAAGGGA 11573 uAGGAAcAccAAcAAGGGAdTsdT sense
    2343-2362 9574 UCCCUUGUUGGUGUUCCUA 11574 UCCCUUGUUGGUGUUCCuAdTsdT antis
    2352-2371 9575 CAACAAGGGAGCAAAUUAG 11575 cAAcAAGGGAGcAAAuuAGdTsdT sense
    2352-2371 9576 CUAAUUUGCUCCCUUGUUG 11576 CuAAUUUGCUCCCUUGUUGdTsdT antis
    2370-2389 9577 GAGAAAUGAACCCAAAUUA 11577 GAGAAAuGAAcccAAAuuAdTsdT sense
    2370-2389 9578 UAAUUUGGGUUCAUUUCUC 11578 uAAUUUGGGUUcAUUUCUCdTsdT antis
    2385-2404 9579 AUUAUACAGAAUUCAAAUU 11579 AuuAuAcAGAAuucAAAuudTsdT sense
    2385-2404 9580 AAUUUGAAUUCUGUAUAAU 11580 AAUUUGAAUUCUGuAuAAUdTsdT antis
    2392-2411 9581 AGAAUUCAAAUUCCCUCAA 11581 AGAAuucAAAuucccucAAdTsdT sense
    2392-2411 9582 UUGAGGGAAUUUGAAUUCU 11582 UUGAGGGAAUUUGAAUUCUdTsdT antis
    2393-2412 9583 GAAUUCAAAUUCCCUCAAA 11583 GAAuucAAAuucccucAAAdTsdT sense
    2393-2412 9584 UUUGAGGGAAUUUGAAUUC 11584 UUUGAGGGAAUUUGAAUUCdTsdT antis
    2403-2422 9585 UCCCUCAAAUCAAGGCACA 11585 ucccucAAAucAAGGcAcAdTsdT sense
    2403-2422 9586 UGUGCCUUGAUUUGAGGGA 11586 UGUGCCUUGAUUUGAGGGAdTsdT antis
    2421-2440 9587 AUCCUUGGACAAAGGUCUU 11587 AuccuuGGAcAAAGGucuudTsdT sense
    2421-2440 9588 AAGACCUUUGUCCAAGGAU 11588 AAGACCUUUGUCcAAGGAUdTsdT antis
    2424-2443 9589 CUUGGACAAAGGUCUUCCG 11589 cuuGGAcAAAGGucuuccGdTsdT sense
    2424-2443 9590 CGGAAGACCUUUGUCCAAG 11590 CGGAAGACCUUUGUCcAAGdTsdT antis
    2454-2473 9591 CACCAGAGGCAAUUGCACU 11591 cAccAGAGGcAAuuGcAcudTsdT sense
    2454-2473 9592 AGUGCAAUUGCCUCUGGUG 11592 AGUGcAAUUGCCUCUGGUGdTsdT antis
    2468-2487 9593 GCACUGUGCAGCCGUCUGC 11593 GcAcuGuGcAGccGucuGcdTsdT sense
    2468-2487 9594 GCAGACGGCUGCACAGUGC 11594 GcAGACGGCUGcAcAGUGCdTsdT antis
    2469-2488 9595 CACUGUGCAGCCGUCUGCU 11595 cAcuGuGcAGccGucuGcudTsdT sense
    2469-2488 9596 AGCAGACGGCUGCACAGUG 11596 AGcAGACGGCUGcAcAGUGdTsdT antis
    2516-2535 9597 CCACUGGAAGCUUGUGCAC 11597 ccAcuGGAAGcuuGuGcAcdTsdT sense
    2516-2535 9598 GUGCACAAGCUUCCAGUGG 11598 GUGcAcAAGCUUCcAGUGGdTsdT antis
    1559-1578 9599 GAGAGCUGCAAGCCAGUGC 11599 GAGAGcuGcAAGccAGuGcdTsdT sense
    1559-1578 9600 GCACUGGCUUGCAGCUCUC 11600 GcACUGGCUUGcAGCUCUCdTsdT antis
    1676-1695 9601 CCACAGGAAGUCAGUUAUA 11601 ccAcAGGAAGucAGuuAuAdTsdT sense
    1676-1695 9602 UAUAACUGACUUCCUGUGG 11602 uAuAACUGACUUCCUGUGGdTsdT antis
    1896-1915 9603 AUGAGGUCUACCUUAACCU 11603 AuGAGGucuAccuuAAccudTsdT sense
    1896-1915 9604 AGGUUAAGGUAGACCUCAU 11604 AGGUuAAGGuAGACCUcAUdTsdT antis
    2262-2281 9605 UGUUGGCUGAAUUGUUGCU 11605 uGuuGGcuGAAuuGuuGcudTsdT sense
    2262-2281 9606 AGCAACAAUUCAGCCAACA 11606 AGcAAcAAUUcAGCcAAcAdTsdT antis
    2270-2289 9607 GAAUUGUUGCUAGGACAAC 11607 GAAuuGuuGcuAGGAcAAcdTsdT sense
    2270-2289 9608 GUUGUCCUAGCAACAAUUC 11608 GUUGUCCuAGcAAcAAUUCdTsdT antis
    1576-1595 9609 GCAGCAGCCUUCAGCUUUU 11609 GcAGcAGccuucAGcuuuudTsdT sense
    1576-1595 9610 AAAAGCUGAAGGCUGCUGC 11610 AAAAGCUGAAGGCUGCUGCdTsdT antis
    1577-1596 9611 CAGCAGCCUUCAGCUUUUG 11611 cAGcAGccuucAGcuuuuGdTsdT sense
    1577-1596 9612 CAAAAGCUGAAGGCUGCUG 11612 cAAAAGCUGAAGGCUGCUGdTsdT antis
    1623-1642 9613 AUGGCAGCAAGGUAACCAC 11613 AuGGcAGcAAGGuAAccAcdTsdT sense
    1623-1642 9614 GUGGUUACCUUGCUGCCAU 11614 GUGGUuACCUUGCUGCcAUdTsdT antis
    1645-1664 9615 AGUGGCAACUCCUGGCCAG 11615 AGuGGcAAcuccuGGccAGdTsdT sense
    1645-1664 9616 CUGGCCAGGAGUUGCCACU 11616 CUGGCcAGGAGUUGCcACUdTsdT antis
    1742-1761 9617 GCCAAACUUUGUGAUUCUG 11617 GccAAAcuuuGuGAuucuGdTsdT sense
    1742-1761 9618 CAGAAUCACAAAGUUUGGC 11618 cAGAAUcAcAAAGUUUGGCdTsdT antis
    1778-1797 9619 AAGAAAGUUCUACAGGACA 11619 AAGAAAGuucuAcAGGAcAdTsdT sense
    1778-1797 9620 UGUCCUGUAGAACUUUCUU 11620 UGUCCUGuAGAACUUUCUUdTsdT antis
    1920-1939 9621 UGGACUAUGUUCCGGAGAC 11621 uGGAcuAuGuuccGGAGAcdTsdT sense
    1920-1939 9622 GUCUCCGGAACAUAGUCCA 11622 GUCUCCGGAAcAuAGUCcAdTsdT antis
    1973-1992 9623 AAGCAGACACUCCCUGUGA 11623 AAGcAGAcAcucccuGuGAdTsdT sense
    1973-1992 9624 UCACAGGGAGUGUCUGCUU 11624 UcAcAGGGAGUGUCUGCUUdTsdT antis
    1984-2003 9625 CCCUGUGAUCUAUGUCAAG 11625 cccuGuGAucuAuGucAAGdTsdT sense
    1984-2003 9626 CUUGACAUAGAUCACAGGG 11626 CUUGAcAuAGAUcAcAGGGdTsdT antis
    2085-2104 9627 UCUUGUUGGAUCCUGAUAC 11627 ucuuGuuGGAuccuGAuAcdTsdT sense
    2085-2104 9628 GUAUCAGGAUCCAACAAGA 11628 GuAUcAGGAUCcAAcAAGAdTsdT antis
    2090-2109 9629 UUGGAUCCUGAUACAGCUG 11629 uuGGAuccuGAuAcAGcuGdTsdT sense
    2090-2109 9630 CAGCUGUAUCAGGAUCCAA 11630 cAGCUGuAUcAGGAUCcAAdTsdT antis
    2170-2189 9631 AUAUAUCUGUUCUCGGUAC 11631 AuAuAucuGuucucGGuAcdTsdT sense
    2170-2189 9632 GUACCGAGAACAGAUAUAU 11632 GuACCGAGAAcAGAuAuAUdTsdT antis
    2200-2219 9633 AGAGUUGAUCUUUGGAGCC 11633 AGAGuuGAucuuuGGAGccdTsdT sense
    2200-2219 9634 GGCUCCAAAGAUCAACUCU 11634 GGCUCcAAAGAUcAACUCUdTsdT antis
    2253-2272 9635 CAGGCUGUGUGUUGGCUGA 11635 cAGGcuGuGuGuuGGcuGAdTsdT sense
    2253-2272 9636 UCAGCCAACACACAGCCUG 11636 UcAGCcAAcAcAcAGCCUGdTsdT antis
    2264-2283 9637 UUGGCUGAAUUGUUGCUAG 11637 uuGGcuGAAuuGuuGcuAGdTsdT sense
    2264-2283 9638 CUAGCAACAAUUCAGCCAA 11638 CuAGcAAcAAUUcAGCcAAdTsdT antis
    2285-2304 9639 CAACCAAUAUUUCCUGGGG 11639 cAAccAAuAuuuccuGGGGdTsdT sense
    2285-2304 9640 CCCCAGGAAAUAUUGGUUG 11640 CCCcAGGAAAuAUUGGUUGdTsdT antis
    2315-2334 9641 GAUCAGUUGGUGGAAAUAA 11641 GAucAGuuGGuGGAAAuAAdTsdT sense
    2315-2334 9642 UUAUUUCCACCAACUGAUC 11642 UuAUUUCcACcAACUGAUCdTsdT antis
    2452-2471 9643 UCCACCAGAGGCAAUUGCA 11643 uccAccAGAGGcAAuuGcAdTsdT sense
    2452-2471 9644 UGCAAUUGCCUCUGGUGGA 11644 UGcAAUUGCCUCUGGUGGAdTsdT antis
    2503-2522 9645 CGCCCGGCUAACACCACUG 11645 cGcccGGcuAAcAccAcuGdTsdT sense
    2503-2522 9646 CAGUGGUGUUAGCCGGGCG 11646 cAGUGGUGUuAGCCGGGCGdTsdT antis
    2504-2523 9647 GCCCGGCUAACACCACUGG 11647 GcccGGcuAAcAccAcuGGdTsdT sense
    2504-2523 9648 CCAGUGGUGUUAGCCGGGC 11648 CcAGUGGUGUuAGCCGGGCdTsdT antis
    1961-1980 9649 UAUAGUCGAGCCAAGCAGA 11649 uAuAGucGAGccAAGcAGAdTsdT sense
    1961-1980 9650 UCUGCUUGGCUCGACUAUA 11650 UCUGCUUGGCUCGACuAuAdTsdT antis
    1699-1718 9651 CACGAAAGUGAUUGGAAAU 11651 cAcGAAAGuGAuuGGAAAudTsdT sense
    1699-1718 9652 AUUUCCAAUCACUUUCGUG 11652 AUUUCcAAUcACUUUCGUGdTsdT antis
    1791-1810 9653 AGGACAAGCGAUUUAAGAA 11653 AGGAcAAGcGAuuuAAGAAdTsdT sense
    1791-1810 9654 UUCUUAAAUCGCUUGUCCU 11654 UUCUuAAAUCGCUUGUCCUdTsdT antis
    1534-1553 9655 GCGACCGAGAACCACCUCC 11655 GcGAccGAGAAccAccuccdTsdT sense
    1534-1553 9656 GGAGGUGGUUCUCGGUCGC 11656 GGAGGUGGUUCUCGGUCGCdTsdT antis
    1899-1918 9657 AGGUCUACCUUAACCUGGU 11657 AGGucuAccuuAAccuGGudTsdT sense
    1899-1918 9658 ACCAGGUUAAGGUAGACCU 11658 ACcAGGUuAAGGuAGACCUdTsdT antis
    1931-1950 9659 CCGGAGACAGUGUACAGAG 11659 ccGGAGAcAGuGuAcAGAGdTsdT sense
    1931-1950 9660 CUCUGUACACUGUCUCCGG 11660 CUCUGuAcACUGUCUCCGGdTsdT antis
    1964-1983 9661 AGUCGAGCCAAGCAGACAC 11661 AGucGAGccAAGcAGAcAcdTsdT sense
    1964-1983 9662 GUGUCUGCUUGGCUCGACU 11662 GUGUCUGCUUGGCUCGACUdTsdT antis
    2056-2075 9663 CUGCCAUCGAGACAUUAAA 11663 cuGccAucGAGAcAuuAAAdTsdT sense
    2056-2075 9664 UUUAAUGUCUCGAUGGCAG 11664 UUuAAUGUCUCGAUGGcAGdTsdT antis
    2155-2174 9665 AGAGCCCAAUGUUUCAUAU 11665 AGAGcccAAuGuuucAuAudTsdT sense
    2155-2174 9666 AUAUGAAACAUUGGGCUCU 11666 AuAUGAAAcAUUGGGCUCUdTsdT antis
    2182-2201 9667 UCGGUACUACAGGGCACCA 11667 ucGGuAcuAcAGGGcAccAdTsdT sense
    2182-2201 9668 UGGUGCCCUGUAGUACCGA 11668 UGGUGCCCUGuAGuACCGAdTsdT antis
    2329-2348 9669 AAUAAUAAAGGUCCUAGGA 11669 AAuAAuAAAGGuccuAGGAdTsdT sense
    2329-2348 9670 UCCUAGGACCUUUAUUAUU 11670 UCCuAGGACCUUuAUuAUUdTsdT antis
    2360-2379 9671 GAGCAAAUUAGAGAAAUGA 11671 GAGcAAAuuAGAGAAAuGAdTsdT sense
    2360-2379 9672 UCAUUUCUCUAAUUUGCUC 11672 UcAUUUCUCuAAUUUGCUCdTsdT antis
    2500-2519 9673 UACCGCCCGGCUAACACCA 11673 uAccGcccGGcuAAcAccAdTsdT sense
    2500-2519 9674 UGGUGUUAGCCGGGCGGUA 11674 UGGUGUuAGCCGGGCGGuAdTsdT antis
    1526-1545 9675 AUGUCGGGGCGACCGAGAA 11675 AuGucGGGGcGAccGAGAAdTsdT sense
    1526-1545 9676 UUCUCGGUCGCCCCGACAU 11676 UUCUCGGUCGCCCCGAcAUdTsdT antis
    1535-1554 9677 CGACCGAGAACCACCUCCU 11677 cGAccGAGAAccAccuccudTsdT sense
    1535-1554 9678 AGGAGGUGGUUCUCGGUCG 11678 AGGAGGUGGUUCUCGGUCGdTsdT antis
    1553-1572 9679 UUUGCGGAGAGCUGCAAGC 11679 uuuGcGGAGAGcuGcAAGcdTsdT sense
    1553-1572 9680 GCUUGCAGCUCUCCGCAAA 11680 GCUUGcAGCUCUCCGcAAAdTsdT antis
    1628-1647 9681 AGCAAGGUAACCACAGUAG 11681 AGcAAGGuAAccAcAGuAGdTsdT sense
    1628-1647 9682 CUACUGUGGUUACCUUGCU 11682 CuACUGUGGUuACCUUGCUdTsdT antis
    1633-1652 9683 GGUAACCACAGUAGUGGCA 11683 GGuAAccAcAGuAGuGGcAdTsdT sense
    1633-1652 9684 UGCCACUACUGUGGUUACC 11684 UGCcACuACUGUGGUuACCdTsdT antis
    1682-1701 9685 GAAGUCAGUUAUACAGACA 11685 GAAGucAGuuAuAcAGAcAdTsdT sense
    1682-1701 9686 UGUCUGUAUAACUGACUUC 11686 UGUCUGuAuAACUGACUUCdTsdT antis
    1684-1703 9687 AGUCAGUUAUACAGACACG 11687 AGucAGuuAuAcAGAcAcGdTsdT sense
    1684-1703 9688 CGUGUCUGUAUAACUGACU 11688 CGUGUCUGuAuAACUGACUdTsdT antis
    1698-1717 9689 ACACGAAAGUGAUUGGAAA 11689 AcAcGAAAGuGAuuGGAAAdTsdT sense
    1698-1717 9690 UUUCCAAUCACUUUCGUGU 11690 UUUCcAAUcACUUUCGUGUdTsdT antis
    1700-1719 9691 ACGAAAGUGAUUGGAAAUG 11691 AcGAAAGuGAuuGGAAAuGdTsdT sense
    1700-1719 9692 CAUUUCCAAUCACUUUCGU 11692 cAUUUCcAAUcACUUUCGUdTsdT antis
    1703-1722 9693 AAAGUGAUUGGAAAUGGAU 11693 AAAGuGAuuGGAAAuGGAudTsdT sense
    1703-1722 9694 AUCCAUUUCCAAUCACUUU 11694 AUCcAUUUCcAAUcACUUUdTsdT antis
    1735-1754 9695 AUAUCAAGCCAAACUUUGU 11695 AuAucAAGccAAAcuuuGudTsdT sense
    1735-1754 9696 ACAAAGUUUGGCUUGAUAU 11696 AcAAAGUUUGGCUUGAuAUdTsdT antis
    1741-1760 9697 AGCCAAACUUUGUGAUUCU 11697 AGccAAAcuuuGuGAuucudTsdT sense
    1741-1760 9698 AGAAUCACAAAGUUUGGCU 11698 AGAAUcAcAAAGUUUGGCUdTsdT antis
    1773-1792 9699 CCAUCAAGAAAGUUCUACA 11699 ccAucAAGAAAGuucuAcAdTsdT sense
    1773-1792 9700 UGUAGAACUUUCUUGAUGG 11700 UGuAGAACUUUCUUGAUGGdTsdT antis
    1774-1793 9701 CAUCAAGAAAGUUCUACAG 11701 cAucAAGAAAGuucuAcAGdTsdT sense
    1774-1793 9702 CUGUAGAACUUUCUUGAUG 11702 CUGuAGAACUUUCUUGAUGdTsdT antis
    1784-1803 9703 GUUCUACAGGACAAGCGAU 11703 GuucuAcAGGAcAAGcGAudTsdT sense
    1784-1803 9704 AUCGCUUGUCCUGUAGAAC 11704 AUCGCUUGUCCUGuAGAACdTsdT antis
    1823-1842 9705 AUCAUGAGAAAGCUAGACC 11705 AucAuGAGAAAGcuAGAccdTsdT sense
    1823-1842 9706 GGUCUAGCUUUCUCAUGAU 11706 GGUCuAGCUUUCUcAUGAUdTsdT antis
    1868-1887 9707 UUCUUCUACUCGAGUGGUG 11707 uucuucuAcucGAGuGGuGdTsdT sense
    1868-1887 9708 CACCACUCGAGUAGAAGAA 11708 cACcACUCGAGuAGAAGAAdTsdT antis
    1876-1895 9709 CUCGAGUGGUGAGAAGAAA 11709 cucGAGuGGuGAGAAGAAAdTsdT sense
    1876-1895 9710 UUUCUUCUCACCACUCGAG 11710 UUUCUUCUcACcACUCGAGdTsdT antis
    1907-1926 9711 CUUAACCUGGUGCUGGACU 11711 cuuAAccuGGuGcuGGAcudTsdT sense
    1907-1926 9712 AGUCCAGCACCAGGUUAAG 11712 AGUCcAGcACcAGGUuAAGdTsdT antis
    1910-1929 9713 AACCUGGUGCUGGACUAUG 11713 AAccuGGuGcuGGAcuAuGdTsdT sense
    1910-1929 9714 CAUAGUCCAGCACCAGGUU 11714 cAuAGUCcAGcACcAGGUUdTsdT antis
    1930-1949 9715 UCCGGAGACAGUGUACAGA 11715 uccGGAGAcAGuGuAcAGAdTsdT sense
    1930-1949 9716 UCUGUACACUGUCUCCGGA 11716 UCUGuAcACUGUCUCCGGAdTsdT antis
    1939-1958 9717 AGUGUACAGAGUCGCCAGA 11717 AGuGuAcAGAGucGccAGAdTsdT sense
    1939-1958 9718 UCUGGCGACUCUGUACACU 11718 UCUGGCGACUCUGuAcACUdTsdT antis
    1940-1959 9719 GUGUACAGAGUCGCCAGAC 11719 GuGuAcAGAGucGccAGAcdTsdT sense
    1940-1959 9720 GUCUGGCGACUCUGUACAC 11720 GUCUGGCGACUCUGuAcACdTsdT antis
    1943-1962 9721 UACAGAGUCGCCAGACACU 11721 uAcAGAGucGccAGAcAcudTsdT sense
    1943-1962 9722 AGUGUCUGGCGACUCUGUA 11722 AGUGUCUGGCGACUCUGuAdTsdT antis
    1946-1965 9723 AGAGUCGCCAGACACUAUA 11723 AGAGucGccAGAcAcuAuAdTsdT sense
    1946-1965 9724 UAUAGUGUCUGGCGACUCU 11724 uAuAGUGUCUGGCGACUCUdTsdT antis
    1948-1967 9725 AGUCGCCAGACACUAUAGU 11725 AGucGccAGAcAcuAuAGudTsdT sense
    1948-1967 9726 ACUAUAGUGUCUGGCGACU 11726 ACuAuAGUGUCUGGCGACUdTsdT antis
    1963-1982 9727 UAGUCGAGCCAAGCAGACA 11727 uAGucGAGccAAGcAGAcAdTsdT sense
    1963-1982 9728 UGUCUGCUUGGCUCGACUA 11728 UGUCUGCUUGGCUCGACuAdTsdT antis
    1987-2006 9729 UGUGAUCUAUGUCAAGUUG 11729 uGuGAucuAuGucAAGuuGdTsdT sense
    1987-2006 9730 CAACUUGACAUAGAUCACA 11730 cAACUUGAcAuAGAUcAcAdTsdT antis
    1991-2010 9731 AUCUAUGUCAAGUUGUAUA 11731 AucuAuGucAAGuuGuAuAdTsdT sense
    1991-2010 9732 UAUACAACUUGACAUAGAU 11732 uAuAcAACUUGAcAuAGAUdTsdT antis
    1992-2011 9733 UCUAUGUCAAGUUGUAUAU 11733 ucuAuGucAAGuuGuAuAudTsdT sense
    1992-2011 9734 AUAUACAACUUGACAUAGA 11734 AuAuAcAACUUGAcAuAGAdTsdT antis
    2000-2019 9735 AAGUUGUAUAUGUAUCAGC 11735 AAGuuGuAuAuGuAucAGcdTsdT sense
    2000-2019 9736 GCUGAUACAUAUACAACUU 11736 GCUGAuAcAuAuAcAACUUdTsdT antis
    2001-2020 9737 AGUUGUAUAUGUAUCAGCU 11737 AGuuGuAuAuGuAucAGcudTsdT sense
    2001-2020 9738 AGCUGAUACAUAUACAACU 11738 AGCUGAuAcAuAuAcAACUdTsdT antis
    2004-2023 9739 UGUAUAUGUAUCAGCUGUU 11739 uGuAuAuGuAucAGcuGuudTsdT sense
    2004-2023 9740 AACAGCUGAUACAUAUACA 11740 AAcAGCUGAuAcAuAuAcAdTsdT antis
    2007-2026 9741 AUAUGUAUCAGCUGUUCAG 11741 AuAuGuAucAGcuGuucAGdTsdT sense
    2007-2026 9742 CUGAACAGCUGAUACAUAU 11742 CUGAAcAGCUGAuAcAuAUdTsdT antis
    2048-2067 9743 UUUGGAAUCUGCCAUCGAG 11743 uuuGGAAucuGccAucGAGdTsdT sense
    2048-2067 9744 CUCGAUGGCAGAUUCCAAA 11744 CUCGAUGGcAGAUUCcAAAdTsdT antis
    2100-2119 9745 AUACAGCUGUAUUAAAACU 11745 AuAcAGcuGuAuuAAAAcudTsdT sense
    2100-2119 9746 AGUUUUAAUACAGCUGUAU 11746 AGUUUuAAuAcAGCUGuAUdTsdT antis
    2107-2126 9747 UGUAUUAAAACUCUGUGAC 11747 uGuAuuAAAAcucuGuGAcdTsdT sense
    2107-2126 9748 GUCACAGAGUUUUAAUACA 11748 GUcAcAGAGUUUuAAuAcAdTsdT antis
    2151-2170 9749 GAGGAGAGCCCAAUGUUUC 11749 GAGGAGAGcccAAuGuuucdTsdT sense
    2151-2170 9750 GAAACAUUGGGCUCUCCUC 11750 GAAAcAUUGGGCUCUCCUCdTsdT antis
    2158-2177 9751 GCCCAAUGUUUCAUAUAUC 11751 GcccAAuGuuucAuAuAucdTsdT sense
    2158-2177 9752 GAUAUAUGAAACAUUGGGC 11752 GAuAuAUGAAAcAUUGGGCdTsdT antis
    2166-2185 9753 UUUCAUAUAUCUGUUCUCG 11753 uuucAuAuAucuGuucucGdTsdT sense
    2166-2185 9754 CGAGAACAGAUAUAUGAAA 11754 CGAGAAcAGAuAuAUGAAAdTsdT antis
    2172-2191 9755 AUAUCUGUUCUCGGUACUA 11755 AuAucuGuucucGGuAcuAdTsdT sense
    2172-2191 9756 UAGUACCGAGAACAGAUAU 11756 uAGuACCGAGAAcAGAuAUdTsdT antis
    2183-2202 9757 CGGUACUACAGGGCACCAG 11757 cGGuAcuAcAGGGcAccAGdTsdT sense
    2183-2202 9758 CUGGUGCCCUGUAGUACCG 11758 CUGGUGCCCUGuAGuACCGdTsdT antis
    2232-2251 9759 CCAGUAUAGAUGUAUGGUC 11759 ccAGuAuAGAuGuAuGGucdTsdT sense
    2232-2251 9760 GACCAUACAUCUAUACUGG 11760 GACcAuAcAUCuAuACUGGdTsdT antis
    2273-2292 9761 UUGUUGCUAGGACAACCAA 11761 uuGuuGcuAGGAcAAccAAdTsdT sense
    2273-2292 9762 UUGGUUGUCCUAGCAACAA 11762 UUGGUUGUCCuAGcAAcAAdTsdT antis
    2274-2293 9763 UGUUGCUAGGACAACCAAU 11763 uGuuGcuAGGAcAAccAAudTsdT sense
    2274-2293 9764 AUUGGUUGUCCUAGCAACA 11764 AUUGGUUGUCCuAGcAAcAdTsdT antis
    2318-2337 9765 CAGUUGGUGGAAAUAAUAA 11765 cAGuuGGuGGAAAuAAuAAdTsdT sense
    2318-2337 9766 UUAUUAUUUCCACCAACUG 11766 UuAUuAUUUCcACcAACUGdTsdT antis
    2361-2380 9767 AGCAAAUUAGAGAAAUGAA 11767 AGcAAAuuAGAGAAAuGAAdTsdT sense
    2361-2380 9768 UUCAUUUCUCUAAUUUGCU 11768 UUcAUUUCUCuAAUUUGCUdTsdT antis
    2380-2399 9769 CCCAAAUUAUACAGAAUUC 11769 cccAAAuuAuAcAGAAuucdTsdT sense
    2380-2399 9770 GAAUUCUGUAUAAUUUGGG 11770 GAAUUCUGuAuAAUUUGGGdTsdT antis
    2400-2419 9771 AAUUCCCUCAAAUCAAGGC 11771 AAuucccucAAAucAAGGcdTsdT sense
    2400-2419 9772 GCCUUGAUUUGAGGGAAUU 11772 GCCUUGAUUUGAGGGAAUUdTsdT antis
    2409-2428 9773 AAAUCAAGGCACAUCCUUG 11773 AAAucAAGGcAcAuccuuGdTsdT sense
    2409-2428 9774 CAAGGAUGUGCCUUGAUUU 11774 cAAGGAUGUGCCUUGAUUUdTsdT antis
    2445-2464 9775 CCCGAACUCCACCAGAGGC 11775 cccGAAcuccAccAGAGGcdTsdT sense
    2445-2464 9776 GCCUCUGGUGGAGUUCGGG 11776 GCCUCUGGUGGAGUUCGGGdTsdT antis
    2479-2498 9777 CCGUCUGCUGGAGUACACA 11777 ccGucuGcuGGAGuAcAcAdTsdT sense
    2479-2498 9778 UGUGUACUCCAGCAGACGG 11778 UGUGuACUCcAGcAGACGGdTsdT antis
    2489-2508 9779 GAGUACACACCUACCGCCC 11779 GAGuAcAcAccuAccGcccdTsdT sense
    2489-2508 9780 GGGCGGUAGGUGUGUACUC 11780 GGGCGGuAGGUGUGuACUCdTsdT antis
    1819-1838 9781 CCAGAUCAUGAGAAAGCUA 11781 ccAGAucAuGAGAAAGcuAdTsdT sense
    1819-1838 9782 UAGCUUUCUCAUGAUCUGG 11782 uAGCUUUCUcAUGAUCUGGdTsdT antis
    2030-2049 9783 CUAGCCUAUAUCCAUUCCU 11783 cuAGccuAuAuccAuuccudTsdT sense
    2030-2049 9784 AGGAAUGGAUAUAGGCUAG 11784 AGGAAUGGAuAuAGGCuAGdTsdT antis
    2154-2173 9785 GAGAGCCCAAUGUUUCAUA 11785 GAGAGcccAAuGuuucAuAdTsdT sense
    2154-2173 9786 UAUGAAACAUUGGGCUCUC 11786 uAUGAAAcAUUGGGCUCUCdTsdT antis
    2184-2203 9787 GGUACUACAGGGCACCAGA 11787 GGuAcuAcAGGGcAccAGAdTsdT sense
    2184-2203 9788 UCUGGUGCCCUGUAGUACC 11788 UCUGGUGCCCUGuAGuACCdTsdT antis
    2190-2209 9789 ACAGGGCACCAGAGUUGAU 11789 AcAGGGcAccAGAGuuGAudTsdT sense
    2190-2209 9790 AUCAACUCUGGUGCCCUGU 11790 AUcAACUCUGGUGCCCUGUdTsdT antis
    2314-2333 9791 GGAUCAGUUGGUGGAAAUA 11791 GGAucAGuuGGuGGAAAuAdTsdT sense
    2314-2333 9792 UAUUUCCACCAACUGAUCC 11792 uAUUUCcACcAACUGAUCCdTsdT antis
    2428-2447 9793 GACAAAGGUCUUCCGGCCC 11793 GAcAAAGGucuuccGGcccdTsdT sense
    2428-2447 9794 GGGCCGGAAGACCUUUGUC 11794 GGGCCGGAAGACCUUUGUCdTsdT antis
    1913-1932 9795 CUGGUGCUGGACUAUGUUC 11795 cuGGuGcuGGAcuAuGuucdTsdT sense
    1913-1932 9796 GAACAUAGUCCAGCACCAG 11796 GAAcAuAGUCcAGcACcAGdTsdT antis
    1530-1549 9797 CGGGGCGACCGAGAACCAC 11797 cGGGGcGAccGAGAAccAcdTsdT sense
    1530-1549 9798 GUGGUUCUCGGUCGCCCCG 11798 GUGGUUCUCGGUCGCCCCGdTsdT antis
    1549-1568 9799 CUCCUUUGCGGAGAGCUGC 11799 cuccuuuGcGGAGAGcuGcdTsdT sense
    1549-1568 9800 GCAGCUCUCCGCAAAGGAG 11800 GcAGCUCUCCGcAAAGGAGdTsdT antis
    1550-1569 9801 UCCUUUGCGGAGAGCUGCA 11801 uccuuuGcGGAGAGcuGcAdTsdT sense
    1550-1569 9802 UGCAGCUCUCCGCAAAGGA 11802 UGcAGCUCUCCGcAAAGGAdTsdT antis
    1610-1629 9803 AGCAGAGAUAAAGAUGGCA 11803 AGcAGAGAuAAAGAuGGcAdTsdT sense
    1610-1629 9804 UGCCAUCUUUAUCUCUGCU 11804 UGCcAUCUUuAUCUCUGCUdTsdT antis
    1642-1661 9805 AGUAGUGGCAACUCCUGGC 11805 AGuAGuGGcAAcuccuGGcdTsdT sense
    1642-1661 9806 GCCAGGAGUUGCCACUACU 11806 GCcAGGAGUUGCcACuACUdTsdT antis
    1643-1662 9807 GUAGUGGCAACUCCUGGCC 11807 GuAGuGGcAAcuccuGGccdTsdT sense
    1643-1662 9808 GGCCAGGAGUUGCCACUAC 11808 GGCcAGGAGUUGCcACuACdTsdT antis
    1696-1715 9809 AGACACGAAAGUGAUUGGA 11809 AGAcAcGAAAGuGAuuGGAdTsdT sense
    1696-1715 9810 UCCAAUCACUUUCGUGUCU 11810 UCcAAUcACUUUCGUGUCUdTsdT antis
    1704-1723 9811 AAGUGAUUGGAAAUGGAUC 11811 AAGuGAuuGGAAAuGGAucdTsdT sense
    1704-1723 9812 GAUCCAUUUCCAAUCACUU 11812 GAUCcAUUUCcAAUcACUUdTsdT antis
    1719-1738 9813 GAUCAUUUGGUGUGGUAUA 11813 GAucAuuuGGuGuGGuAuAdTsdT sense
    1719-1738 9814 UAUACCACACCAAAUGAUC 11814 uAuACcAcACcAAAUGAUCdTsdT antis
    1728-1747 9815 GUGUGGUAUAUCAAGCCAA 11815 GuGuGGuAuAucAAGccAAdTsdT sense
    1728-1747 9816 UUGGCUUGAUAUACCACAC 11816 UUGGCUUGAuAuACcAcACdTsdT antis
    1731-1750 9817 UGGUAUAUCAAGCCAAACU 11817 uGGuAuAucAAGccAAAcudTsdT sense
    1731-1750 9818 AGUUUGGCUUGAUAUACCA 11818 AGUUUGGCUUGAuAuACcAdTsdT antis
    1732-1751 9819 GGUAUAUCAAGCCAAACUU 11819 GGuAuAucAAGccAAAcuudTsdT sense
    1732-1751 9820 AAGUUUGGCUUGAUAUACC 11820 AAGUUUGGCUUGAuAuACCdTsdT antis
    1733-1752 9821 GUAUAUCAAGCCAAACUUU 11821 GuAuAucAAGccAAAcuuudTsdT sense
    1733-1752 9822 AAAGUUUGGCUUGAUAUAC 11822 AAAGUUUGGCUUGAuAuACdTsdT antis
    1768-1787 9823 GGUUGCCAUCAAGAAAGUU 11823 GGuuGccAucAAGAAAGuudTsdT sense
    1768-1787 9824 AACUUUCUUGAUGGCAACC 11824 AACUUUCUUGAUGGcAACCdTsdT antis
    1800-1819 9825 GAUUUAAGAACCGAGAGCU 11825 GAuuuAAGAAccGAGAGcudTsdT sense
    1800-1819 9826 AGCUCUCGGUUCUUAAAUC 11826 AGCUCUCGGUUCUuAAAUCdTsdT antis
    1802-1821 9827 UUUAAGAACCGAGAGCUCC 11827 uuuAAGAAccGAGAGcuccdTsdT sense
    1802-1821 9828 GGAGCUCUCGGUUCUUAAA 11828 GGAGCUCUCGGUUCUuAAAdTsdT antis
    1821-1840 9829 AGAUCAUGAGAAAGCUAGA 11829 AGAucAuGAGAAAGcuAGAdTsdT sense
    1821-1840 9830 UCUAGCUUUCUCAUGAUCU 11830 UCuAGCUUUCUcAUGAUCUdTsdT antis
    1830-1849 9831 GAAAGCUAGACCACUGUAA 11831 GAAAGcuAGAccAcuGuAAdTsdT sense
    1830-1849 9832 UUACAGUGGUCUAGCUUUC 11832 UuAcAGUGGUCuAGCUUUCdTsdT antis
    1831-1850 9833 AAAGCUAGACCACUGUAAC 11833 AAAGcuAGAccAcuGuAAcdTsdT sense
    1831-1850 9834 GUUACAGUGGUCUAGCUUU 11834 GUuAcAGUGGUCuAGCUUUdTsdT antis
    1856-1875 9835 CGACUGCGGUAUUUCUUCU 11835 cGAcuGcGGuAuuucuucudTsdT sense
    1856-1875 9836 AGAAGAAAUACCGCAGUCG 11836 AGAAGAAAuACCGcAGUCGdTsdT antis
    1857-1876 9837 GACUGCGGUAUUUCUUCUA 11837 GAcuGcGGuAuuucuucuAdTsdT sense
    1857-1876 9838 UAGAAGAAAUACCGCAGUC 11838 uAGAAGAAAuACCGcAGUCdTsdT antis
    1875-1894 9839 ACUCGAGUGGUGAGAAGAA 11839 AcucGAGuGGuGAGAAGAAdTsdT sense
    1875-1894 9840 UUCUUCUCACCACUCGAGU 11840 UUCUUCUcACcACUCGAGUdTsdT antis
    1877-1896 9841 UCGAGUGGUGAGAAGAAAG 11841 ucGAGuGGuGAGAAGAAAGdTsdT sense
    1877-1896 9842 CUUUCUUCUCACCACUCGA 11842 CUUUCUUCUcACcACUCGAdTsdT antis
    1897-1916 9843 UGAGGUCUACCUUAACCUG 11843 uGAGGucuAccuuAAccuGdTsdT sense
    1897-1916 9844 CAGGUUAAGGUAGACCUCA 11844 cAGGUuAAGGuAGACCUcAdTsdT antis
    1908-1927 9845 UUAACCUGGUGCUGGACUA 11845 uuAAccuGGuGcuGGAcuAdTsdT sense
    1908-1927 9846 UAGUCCAGCACCAGGUUAA 11846 uAGUCcAGcACcAGGUuAAdTsdT antis
    1923-1942 9847 ACUAUGUUCCGGAGACAGU 11847 AcuAuGuuccGGAGAcAGudTsdT sense
    1923-1942 9848 ACUGUCUCCGGAACAUAGU 11848 ACUGUCUCCGGAAcAuAGUdTsdT antis
    1928-1947 9849 GUUCCGGAGACAGUGUACA 11849 GuuccGGAGAcAGuGuAcAdTsdT sense
    1928-1947 9850 UGUACACUGUCUCCGGAAC 11850 UGuAcACUGUCUCCGGAACdTsdT antis
    1934-1953 9851 GAGACAGUGUACAGAGUCG 11851 GAGAcAGuGuAcAGAGucGdTsdT sense
    1934-1953 9852 CGACUCUGUACACUGUCUC 11852 CGACUCUGuAcACUGUCUCdTsdT antis
    1951-1970 9853 CGCCAGACACUAUAGUCGA 11853 cGccAGAcAcuAuAGucGAdTsdT sense
    1951-1970 9854 UCGACUAUAGUGUCUGGCG 11854 UCGACuAuAGUGUCUGGCGdTsdT antis
    1981-2000 9855 ACUCCCUGUGAUCUAUGUC 11855 AcucccuGuGAucuAuGucdTsdT sense
    1981-2000 9856 GACAUAGAUCACAGGGAGU 11856 GAcAuAGAUcAcAGGGAGUdTsdT antis
    1983-2002 9857 UCCCUGUGAUCUAUGUCAA 11857 ucccuGuGAucuAuGucAAdTsdT sense
    1983-2002 9858 UUGACAUAGAUCACAGGGA 11858 UUGAcAuAGAUcAcAGGGAdTsdT antis
    1994-2013 9859 UAUGUCAAGUUGUAUAUGU 11859 uAuGucAAGuuGuAuAuGudTsdT sense
    1994-2013 9860 ACAUAUACAACUUGACAUA 11860 AcAuAuAcAACUUGAcAuAdTsdT antis
    2003-2022 9861 UUGUAUAUGUAUCAGCUGU 11861 uuGuAuAuGuAucAGcuGudTsdT sense
    2003-2022 9862 ACAGCUGAUACAUAUACAA 11862 AcAGCUGAuAcAuAuAcAAdTsdT antis
    2067-2086 9863 ACAUUAAACCACAGAACCU 11863 AcAuuAAAccAcAGAAccudTsdT sense
    2067-2086 9864 AGGUUCUGUGGUUUAAUGU 11864 AGGUUCUGUGGUUuAAUGUdTsdT antis
    2077-2096 9865 ACAGAACCUCUUGUUGGAU 11865 AcAGAAccucuuGuuGGAudTsdT sense
    2077-2096 9866 AUCCAACAAGAGGUUCUGU 11866 AUCcAAcAAGAGGUUCUGUdTsdT antis
    2079-2098 9867 AGAACCUCUUGUUGGAUCC 11867 AGAAccucuuGuuGGAuccdTsdT sense
    2079-2098 9868 GGAUCCAACAAGAGGUUCU 11868 GGAUCcAAcAAGAGGUUCUdTsdT antis
    2087-2106 9869 UUGUUGGAUCCUGAUACAG 11869 uuGuuGGAuccuGAuAcAGdTsdT sense
    2087-2106 9870 CUGUAUCAGGAUCCAACAA 11870 CUGuAUcAGGAUCcAAcAAdTsdT antis
    2093-2112 9871 GAUCCUGAUACAGCUGUAU 11871 GAuccuGAuAcAGcuGuAudTsdT sense
    2093-2112 9872 AUACAGCUGUAUCAGGAUC 11872 AuAcAGCUGuAUcAGGAUCdTsdT antis
    2099-2118 9873 GAUACAGCUGUAUUAAAAC 11873 GAuAcAGcuGuAuuAAAAcdTsdT sense
    2099-2118 9874 GUUUUAAUACAGCUGUAUC 11874 GUUUuAAuAcAGCUGuAUCdTsdT antis
    2135-2154 9875 GCAAAGCAGCUGGUCCGAG 11875 GcAAAGcAGcuGGuccGAGdTsdT sense
    2135-2154 9876 CUCGGACCAGCUGCUUUGC 11876 CUCGGACcAGCUGCUUUGCdTsdT antis
    2150-2169 9877 CGAGGAGAGCCCAAUGUUU 11877 cGAGGAGAGcccAAuGuuudTsdT sense
    2150-2169 9878 AAACAUUGGGCUCUCCUCG 11878 AAAcAUUGGGCUCUCCUCGdTsdT antis
    2157-2176 9879 AGCCCAAUGUUUCAUAUAU 11879 AGcccAAuGuuucAuAuAudTsdT sense
    2157-2176 9880 AUAUAUGAAACAUUGGGCU 11880 AuAuAUGAAAcAUUGGGCUdTsdT antis
    2198-2217 9881 CCAGAGUUGAUCUUUGGAG 11881 ccAGAGuuGAucuuuGGAGdTsdT sense
    2198-2217 9882 CUCCAAAGAUCAACUCUGG 11882 CUCcAAAGAUcAACUCUGGdTsdT antis
    2199-2218 9883 CAGAGUUGAUCUUUGGAGC 11883 cAGAGuuGAucuuuGGAGcdTsdT sense
    2199-2218 9884 GCUCCAAAGAUCAACUCUG 11884 GCUCcAAAGAUcAACUCUGdTsdT antis
    2216-2235 9885 GCCACUGAUUACACGUCCA 11885 GccAcuGAuuAcAcGuccAdTsdT sense
    2216-2235 9886 UGGACGUGUAAUCAGUGGC 11886 UGGACGUGuAAUcAGUGGCdTsdT antis
    2237-2256 9887 AUAGAUGUAUGGUCUGCAG 11887 AuAGAuGuAuGGucuGcAGdTsdT sense
    2237-2256 9888 CUGCAGACCAUACAUCUAU 11888 CUGcAGACcAuAcAUCuAUdTsdT antis
    2243-2262 9889 GUAUGGUCUGCAGGCUGUG 11889 GuAuGGucuGcAGGcuGuGdTsdT sense
    2243-2262 9890 CACAGCCUGCAGACCAUAC 11890 cAcAGCCUGcAGACcAuACdTsdT antis
    2272-2291 9891 AUUGUUGCUAGGACAACCA 11891 AuuGuuGcuAGGAcAAccAdTsdT sense
    2272-2291 9892 UGGUUGUCCUAGCAACAAU 11892 UGGUUGUCCuAGcAAcAAUdTsdT antis
    2283-2302 9893 GACAACCAAUAUUUCCUGG 11893 GAcAAccAAuAuuuccuGGdTsdT sense
    2283-2302 9894 CCAGGAAAUAUUGGUUGUC 11894 CcAGGAAAuAUUGGUUGUCdTsdT antis
    2291-2310 9895 AUAUUUCCUGGGGACAGUG 11895 AuAuuuccuGGGGAcAGuGdTsdT sense
    2291-2310 9896 CACUGUCCCCAGGAAAUAU 11896 cACUGUCCCcAGGAAAuAUdTsdT antis
    2311-2330 9897 UGUGGAUCAGUUGGUGGAA 11897 uGuGGAucAGuuGGuGGAAdTsdT sense
    2311-2330 9898 UUCCACCAACUGAUCCACA 11898 UUCcACcAACUGAUCcAcAdTsdT antis
    2353-2372 9899 AACAAGGGAGCAAAUUAGA 11899 AAcAAGGGAGcAAAuuAGAdTsdT sense
    2353-2372 9900 UCUAAUUUGCUCCCUUGUU 11900 UCuAAUUUGCUCCCUUGUUdTsdT antis
    2359-2378 9901 GGAGCAAAUUAGAGAAAUG 11901 GGAGcAAAuuAGAGAAAuGdTsdT sense
    2359-2378 9902 CAUUUCUCUAAUUUGCUCC 11902 cAUUUCUCuAAUUUGCUCCdTsdT antis
    2379-2398 9903 ACCCAAAUUAUACAGAAUU 11903 AcccAAAuuAuAcAGAAuudTsdT sense
    2379-2398 9904 AAUUCUGUAUAAUUUGGGU 11904 AAUUCUGuAuAAUUUGGGUdTsdT antis
    2408-2427 9905 CAAAUCAAGGCACAUCCUU 11905 cAAAucAAGGcAcAuccuudTsdT sense
    2408-2427 9906 AAGGAUGUGCCUUGAUUUG 11906 AAGGAUGUGCCUUGAUUUGdTsdT antis
    2412-2431 9907 UCAAGGCACAUCCUUGGAC 11907 ucAAGGcAcAuccuuGGAcdTsdT sense
    2412-2431 9908 GUCCAAGGAUGUGCCUUGA 11908 GUCcAAGGAUGUGCCUUGAdTsdT antis
    2438-2457 9909 UUCCGGCCCCGAACUCCAC 11909 uuccGGccccGAAcuccAcdTsdT sense
    2438-2457 9910 GUGGAGUUCGGGGCCGGAA 11910 GUGGAGUUCGGGGCCGGAAdTsdT antis
    2476-2495 9911 CAGCCGUCUGCUGGAGUAC 11911 cAGccGucuGcuGGAGuAcdTsdT sense
    2476-2495 9912 GUACUCCAGCAGACGGCUG 11912 GuACUCcAGcAGACGGCUGdTsdT antis
    2477-2496 9913 AGCCGUCUGCUGGAGUACA 11913 AGccGucuGcuGGAGuAcAdTsdT sense
    2477-2496 9914 UGUACUCCAGCAGACGGCU 11914 UGuACUCcAGcAGACGGCUdTsdT antis
    2478-2497 9915 GCCGUCUGCUGGAGUACAC 11915 GccGucuGcuGGAGuAcAcdTsdT sense
    2478-2497 9916 GUGUACUCCAGCAGACGGC 11916 GUGuACUCcAGcAGACGGCdTsdT antis
    2484-2503 9917 UGCUGGAGUACACACCUAC 11917 uGcuGGAGuAcAcAccuAcdTsdT sense
    2484-2503 9918 GUAGGUGUGUACUCCAGCA 11918 GuAGGUGUGuACUCcAGcAdTsdT antis
    1527-1546 9919 UGUCGGGGCGACCGAGAAC 11919 uGucGGGGcGAccGAGAAcdTsdT sense
    1527-1546 9920 GUUCUCGGUCGCCCCGACA 11920 GUUCUCGGUCGCCCCGAcAdTsdT antis
    1531-1550 9921 GGGGCGACCGAGAACCACC 11921 GGGGcGAccGAGAAccAccdTsdT sense
    1531-1550 9922 GGUGGUUCUCGGUCGCCCC 11922 GGUGGUUCUCGGUCGCCCCdTsdT antis
    1536-1555 9923 GACCGAGAACCACCUCCUU 11923 GAccGAGAAccAccuccuudTsdT sense
    1536-1555 9924 AAGGAGGUGGUUCUCGGUC 11924 AAGGAGGUGGUUCUCGGUCdTsdT antis
    1542-1561 9925 GAACCACCUCCUUUGCGGA 11925 GAAccAccuccuuuGcGGAdTsdT sense
    1542-1561 9926 UCCGCAAAGGAGGUGGUUC 11926 UCCGcAAAGGAGGUGGUUCdTsdT antis
    1552-1571 9927 CUUUGCGGAGAGCUGCAAG 11927 cuuuGcGGAGAGcuGcAAGdTsdT sense
    1552-1571 9928 CUUGCAGCUCUCCGCAAAG 11928 CUUGcAGCUCUCCGcAAAGdTsdT antis
    1556-1575 9929 GCGGAGAGCUGCAAGCCAG 11929 GcGGAGAGcuGcAAGccAGdTsdT sense
    1556-1575 9930 CUGGCUUGCAGCUCUCCGC 11930 CUGGCUUGcAGCUCUCCGCdTsdT antis
    1564-1583 9931 CUGCAAGCCAGUGCAGCAG 11931 cuGcAAGccAGuGcAGcAGdTsdT sense
    1564-1583 9932 CUGCUGCACUGGCUUGCAG 11932 CUGCUGcACUGGCUUGcAGdTsdT antis
    1572-1591 9933 CAGUGCAGCAGCCUUCAGC 11933 cAGuGcAGcAGccuucAGcdTsdT sense
    1572-1591 9934 GCUGAAGGCUGCUGCACUG 11934 GCUGAAGGCUGCUGcACUGdTsdT antis
    1578-1597 9935 AGCAGCCUUCAGCUUUUGG 11935 AGcAGccuucAGcuuuuGGdTsdT sense
    1578-1597 9936 CCAAAAGCUGAAGGCUGCU 11936 CcAAAAGCUGAAGGCUGCUdTsdT antis
    1579-1598 9937 GCAGCCUUCAGCUUUUGGU 11937 GcAGccuucAGcuuuuGGudTsdT sense
    1579-1598 9938 ACCAAAAGCUGAAGGCUGC 11938 ACcAAAAGCUGAAGGCUGCdTsdT antis
    1581-1600 9939 AGCCUUCAGCUUUUGGUAG 11939 AGccuucAGcuuuuGGuAGdTsdT sense
    1581-1600 9940 CUACCAAAAGCUGAAGGCU 11940 CuACcAAAAGCUGAAGGCUdTsdT antis
    1582-1601 9941 GCCUUCAGCUUUUGGUAGC 11941 GccuucAGcuuuuGGuAGcdTsdT sense
    1582-1601 9942 GCUACCAAAAGCUGAAGGC 11942 GCuACcAAAAGCUGAAGGCdTsdT antis
    1585-1604 9943 UUCAGCUUUUGGUAGCAUG 11943 uucAGcuuuuGGuAGcAuGdTsdT sense
    1585-1604 9944 CAUGCUACCAAAAGCUGAA 11944 cAUGCuACcAAAAGCUGAAdTsdT antis
    1587-1606 9945 CAGCUUUUGGUAGCAUGAA 11945 cAGcuuuuGGuAGcAuGAAdTsdT sense
    1587-1606 9946 UUCAUGCUACCAAAAGCUG 11946 UUcAUGCuACcAAAAGCUGdTsdT antis
    1588-1607 9947 AGCUUUUGGUAGCAUGAAA 11947 AGcuuuuGGuAGcAuGAAAdTsdT sense
    1588-1607 9948 UUUCAUGCUACCAAAAGCU 11948 UUUcAUGCuACcAAAAGCUdTsdT antis
    1598-1617 9949 AGCAUGAAAGUUAGCAGAG 11949 AGcAuGAAAGuuAGcAGAGdTsdT sense
    1598-1617 9950 CUCUGCUAACUUUCAUGCU 11950 CUCUGCuAACUUUcAUGCUdTsdT antis
    1602-1621 9951 UGAAAGUUAGCAGAGAUAA 11951 uGAAAGuuAGcAGAGAuAAdTsdT sense
    1602-1621 9952 UUAUCUCUGCUAACUUUCA 11952 UuAUCUCUGCuAACUUUcAdTsdT antis
    1618-1637 9953 UAAAGAUGGCAGCAAGGUA 11953 uAAAGAuGGcAGcAAGGuAdTsdT sense
    1618-1637 9954 UACCUUGCUGCCAUCUUUA 11954 uACCUUGCUGCcAUCUUuAdTsdT antis
    1619-1638 9955 AAAGAUGGCAGCAAGGUAA 11955 AAAGAuGGcAGcAAGGuAAdTsdT sense
    1619-1638 9956 UUACCUUGCUGCCAUCUUU 11956 UuACCUUGCUGCcAUCUUUdTsdT antis
    1625-1644 9957 GGCAGCAAGGUAACCACAG 11957 GGcAGcAAGGuAAccAcAGdTsdT sense
    1625-1644 9958 CUGUGGUUACCUUGCUGCC 11958 CUGUGGUuACCUUGCUGCCdTsdT antis
    1627-1646 9959 CAGCAAGGUAACCACAGUA 11959 cAGcAAGGuAAccAcAGuAdTsdT sense
    1627-1646 9960 UACUGUGGUUACCUUGCUG 11960 uACUGUGGUuACCUUGCUGdTsdT antis
    1636-1655 9961 AACCACAGUAGUGGCAACU 11961 AAccAcAGuAGuGGcAAcudTsdT sense
    1636-1655 9962 AGUUGCCACUACUGUGGUU 11962 AGUUGCcACuACUGUGGUUdTsdT antis
    1637-1656 9963 ACCACAGUAGUGGCAACUC 11963 AccAcAGuAGuGGcAAcucdTsdT sense
    1637-1656 9964 GAGUUGCCACUACUGUGGU 11964 GAGUUGCcACuACUGUGGUdTsdT antis
    1646-1665 9965 GUGGCAACUCCUGGCCAGG 11965 GuGGcAAcuccuGGccAGGdTsdT sense
    1646-1665 9966 CCUGGCCAGGAGUUGCCAC 11966 CCUGGCcAGGAGUUGCcACdTsdT antis
    1648-1667 9967 GGCAACUCCUGGCCAGGGU 11967 GGcAAcuccuGGccAGGGudTsdT sense
    1648-1667 9968 ACCCUGGCCAGGAGUUGCC 11968 ACCCUGGCcAGGAGUUGCCdTsdT antis
    1649-1668 9969 GCAACUCCUGGCCAGGGUC 11969 GcAAcuccuGGccAGGGucdTsdT sense
    1649-1668 9970 GACCCUGGCCAGGAGUUGC 11970 GACCCUGGCcAGGAGUUGCdTsdT antis
    1651-1670 9971 AACUCCUGGCCAGGGUCCU 11971 AAcuccuGGccAGGGuccudTsdT sense
    1651-1670 9972 AGGACCCUGGCCAGGAGUU 11972 AGGACCCUGGCcAGGAGUUdTsdT antis
    1666-1685 9973 UCCUGACAGGCCACAGGAA 11973 uccuGAcAGGccAcAGGAAdTsdT sense
    1666-1685 9974 UUCCUGUGGCCUGUCAGGA 11974 UUCCUGUGGCCUGUcAGGAdTsdT antis
    1667-1686 9975 CCUGACAGGCCACAGGAAG 11975 ccuGAcAGGccAcAGGAAGdTsdT sense
    1667-1686 9976 CUUCCUGUGGCCUGUCAGG 11976 CUUCCUGUGGCCUGUcAGGdTsdT antis
    1669-1688 9977 UGACAGGCCACAGGAAGUC 11977 uGAcAGGccAcAGGAAGucdTsdT sense
    1669-1688 9978 GACUUCCUGUGGCCUGUCA 11978 GACUUCCUGUGGCCUGUcAdTsdT antis
    1670-1689 9979 GACAGGCCACAGGAAGUCA 11979 GAcAGGccAcAGGAAGucAdTsdT sense
    1670-1689 9980 UGACUUCCUGUGGCCUGUC 11980 UGACUUCCUGUGGCCUGUCdTsdT antis
    1685-1704 9981 GUCAGUUAUACAGACACGA 11981 GucAGuuAuAcAGAcAcGAdTsdT sense
    1685-1704 9982 UCGUGUCUGUAUAACUGAC 11982 UCGUGUCUGuAuAACUGACdTsdT antis
    1687-1706 9983 CAGUUAUACAGACACGAAA 11983 cAGuuAuAcAGAcAcGAAAdTsdT sense
    1687-1706 9984 UUUCGUGUCUGUAUAACUG 11984 UUUCGUGUCUGuAuAACUGdTsdT antis
    1689-1708 9985 GUUAUACAGACACGAAAGU 11985 GuuAuAcAGAcAcGAAAGudTsdT sense
    1689-1708 9986 ACUUUCGUGUCUGUAUAAC 11986 ACUUUCGUGUCUGuAuAACdTsdT antis
    1691-1710 9987 UAUACAGACACGAAAGUGA 11987 uAuAcAGAcAcGAAAGuGAdTsdT sense
    1691-1710 9988 UCACUUUCGUGUCUGUAUA 11988 UcACUUUCGUGUCUGuAuAdTsdT antis
    1693-1712 9989 UACAGACACGAAAGUGAUU 11989 uAcAGAcAcGAAAGuGAuudTsdT sense
    1693-1712 9990 AAUCACUUUCGUGUCUGUA 11990 AAUcACUUUCGUGUCUGuAdTsdT antis
    1701-1720 9991 CGAAAGUGAUUGGAAAUGG 11991 cGAAAGuGAuuGGAAAuGGdTsdT sense
    1701-1720 9992 CCAUUUCCAAUCACUUUCG 11992 CcAUUUCcAAUcACUUUCGdTsdT antis
    1707-1726 9993 UGAUUGGAAAUGGAUCAUU 11993 uGAuuGGAAAuGGAucAuudTsdT sense
    1707-1726 9994 AAUGAUCCAUUUCCAAUCA 11994 AAUGAUCcAUUUCcAAUcAdTsdT antis
    1717-1736 9995 UGGAUCAUUUGGUGUGGUA 11995 uGGAucAuuuGGuGuGGuAdTsdT sense
    1717-1736 9996 UACCACACCAAAUGAUCCA 11996 uACcAcACcAAAUGAUCcAdTsdT antis
    1721-1740 9997 UCAUUUGGUGUGGUAUAUC 11997 ucAuuuGGuGuGGuAuAucdTsdT sense
    1721-1740 9998 GAUAUACCACACCAAAUGA 11998 GAuAuACcAcACcAAAUGAdTsdT antis
    1729-1748 9999 UGUGGUAUAUCAAGCCAAA 11999 uGuGGuAuAucAAGccAAAdTsdT sense
    1729-1748 10000 UUUGGCUUGAUAUACCACA 12000 UUUGGCUUGAuAuACcAcAdTsdT antis
    1734-1753 10001 UAUAUCAAGCCAAACUUUG 12001 uAuAucAAGccAAAcuuuGdTsdT sense
    1734-1753 10002 CAAAGUUUGGCUUGAUAUA 12002 cAAAGUUUGGCUUGAuAuAdTsdT antis
    1736-1755 10003 UAUCAAGCCAAACUUUGUG 12003 uAucAAGccAAAcuuuGuGdTsdT sense
    1736-1755 10004 CACAAAGUUUGGCUUGAUA 12004 cAcAAAGUUUGGCUUGAuAdTsdT antis
    1737-1756 10005 AUCAAGCCAAACUUUGUGA 12005 AucAAGccAAAcuuuGuGAdTsdT sense
    1737-1756 10006 UCACAAAGUUUGGCUUGAU 12006 UcAcAAAGUUUGGCUUGAUdTsdT antis
    1749-1768 10007 UUUGUGAUUCUGGAGAACU 12007 uuuGuGAuucuGGAGAAcudTsdT sense
    1749-1768 10008 AGUUCUCCAGAAUCACAAA 12008 AGUUCUCcAGAAUcAcAAAdTsdT antis
    1759-1778 10009 UGGAGAACUGGUUGCCAUC 12009 uGGAGAAcuGGuuGccAucdTsdT sense
    1759-1778 10010 GAUGGCAACCAGUUCUCCA 12010 GAUGGcAACcAGUUCUCcAdTsdT antis
    1760-1779 10011 GGAGAACUGGUUGCCAUCA 12011 GGAGAAcuGGuuGccAucAdTsdT sense
    1760-1779 10012 UGAUGGCAACCAGUUCUCC 12012 UGAUGGcAACcAGUUCUCCdTsdT antis
    1767-1786 10013 UGGUUGCCAUCAAGAAAGU 12013 uGGuuGccAucAAGAAAGudTsdT sense
    1767-1786 10014 ACUUUCUUGAUGGCAACCA 12014 ACUUUCUUGAUGGcAACcAdTsdT antis
    1769-1788 10015 GUUGCCAUCAAGAAAGUUC 12015 GuuGccAucAAGAAAGuucdTsdT sense
    1769-1788 10016 GAACUUUCUUGAUGGCAAC 12016 GAACUUUCUUGAUGGcAACdTsdT antis
    1770-1789 10017 UUGCCAUCAAGAAAGUUCU 12017 uuGccAucAAGAAAGuucudTsdT sense
    1770-1789 10018 AGAACUUUCUUGAUGGCAA 12018 AGAACUUUCUUGAUGGcAAdTsdT antis
    1775-1794 10019 AUCAAGAAAGUUCUACAGG 12019 AucAAGAAAGuucuAcAGGdTsdT sense
    1775-1794 10020 CCUGUAGAACUUUCUUGAU 12020 CCUGuAGAACUUUCUUGAUdTsdT antis
    1783-1802 10021 AGUUCUACAGGACAAGCGA 12021 AGuucuAcAGGAcAAGcGAdTsdT sense
    1783-1802 10022 UCGCUUGUCCUGUAGAACU 12022 UCGCUUGUCCUGuAGAACUdTsdT antis
    1787-1806 10023 CUACAGGACAAGCGAUUUA 12023 cuAcAGGAcAAGcGAuuuAdTsdT sense
    1787-1806 10024 UAAAUCGCUUGUCCUGUAG 12024 uAAAUCGCUUGUCCUGuAGdTsdT antis
    1806-1825 10025 AGAACCGAGAGCUCCAGAU 12025 AGAAccGAGAGcuccAGAudTsdT sense
    1806-1825 10026 AUCUGGAGCUCUCGGUUCU 12026 AUCUGGAGCUCUCGGUUCUdTsdT antis
    1810-1829 10027 CCGAGAGCUCCAGAUCAUG 12027 ccGAGAGcuccAGAucAuGdTsdT sense
    1810-1829 10028 CAUGAUCUGGAGCUCUCGG 12028 cAUGAUCUGGAGCUCUCGGdTsdT antis
    1815-1834 10029 AGCUCCAGAUCAUGAGAAA 12029 AGcuccAGAucAuGAGAAAdTsdT sense
    1815-1834 10030 UUUCUCAUGAUCUGGAGCU 12030 UUUCUcAUGAUCUGGAGCUdTsdT antis
    1816-1835 10031 GCUCCAGAUCAUGAGAAAG 12031 GcuccAGAucAuGAGAAAGdTsdT sense
    1816-1835 10032 CUUUCUCAUGAUCUGGAGC 12032 CUUUCUcAUGAUCUGGAGCdTsdT antis
    1817-1836 10033 CUCCAGAUCAUGAGAAAGC 12033 cuccAGAucAuGAGAAAGcdTsdT sense
    1817-1836 10034 GCUUUCUCAUGAUCUGGAG 12034 GCUUUCUcAUGAUCUGGAGdTsdT antis
    1820-1839 10035 CAGAUCAUGAGAAAGCUAG 12035 cAGAucAuGAGAAAGcuAGdTsdT sense
    1820-1839 10036 CUAGCUUUCUCAUGAUCUG 12036 CuAGCUUUCUcAUGAUCUGdTsdT antis
    1824-1843 10037 UCAUGAGAAAGCUAGACCA 12037 ucAuGAGAAAGcuAGAccAdTsdT sense
    1824-1843 10038 UGGUCUAGCUUUCUCAUGA 12038 UGGUCuAGCUUUCUcAUGAdTsdT antis
    1825-1844 10039 CAUGAGAAAGCUAGACCAC 12039 cAuGAGAAAGcuAGAccAcdTsdT sense
    1825-1844 10040 GUGGUCUAGCUUUCUCAUG 12040 GUGGUCuAGCUUUCUcAUGdTsdT antis
    1826-1845 10041 AUGAGAAAGCUAGACCACU 12041 AuGAGAAAGcuAGAccAcudTsdT sense
    1826-1845 10042 AGUGGUCUAGCUUUCUCAU 12042 AGUGGUCuAGCUUUCUcAUdTsdT antis
    1858-1877 10043 ACUGCGGUAUUUCUUCUAC 12043 AcuGcGGuAuuucuucuAcdTsdT sense
    1858-1877 10044 GUAGAAGAAAUACCGCAGU 12044 GuAGAAGAAAuACCGcAGUdTsdT antis
    1866-1885 10045 AUUUCUUCUACUCGAGUGG 12045 AuuucuucuAcucGAGuGGdTsdT sense
    1866-1885 10046 CCACUCGAGUAGAAGAAAU 12046 CcACUCGAGuAGAAGAAAUdTsdT antis
    1869-1888 10047 UCUUCUACUCGAGUGGUGA 12047 ucuucuAcucGAGuGGuGAdTsdT sense
    1869-1888 10048 UCACCACUCGAGUAGAAGA 12048 UcACcACUCGAGuAGAAGAdTsdT antis
    1878-1897 10049 CGAGUGGUGAGAAGAAAGA 12049 cGAGuGGuGAGAAGAAAGAdTsdT sense
    1878-1897 10050 UCUUUCUUCUCACCACUCG 12050 UCUUUCUUCUcACcACUCGdTsdT antis
    1890-1909 10051 AGAAAGAUGAGGUCUACCU 12051 AGAAAGAuGAGGucuAccudTsdT sense
    1890-1909 10052 AGGUAGACCUCAUCUUUCU 12052 AGGuAGACCUcAUCUUUCUdTsdT antis
    1891-1910 10053 GAAAGAUGAGGUCUACCUU 12053 GAAAGAuGAGGucuAccuudTsdT sense
    1891-1910 10054 AAGGUAGACCUCAUCUUUC 12054 AAGGuAGACCUcAUCUUUCdTsdT antis
    1898-1917 10055 GAGGUCUACCUUAACCUGG 12055 GAGGucuAccuuAAccuGGdTsdT sense
    1898-1917 10056 CCAGGUUAAGGUAGACCUC 12056 CcAGGUuAAGGuAGACCUCdTsdT antis
    1903-1922 10057 CUACCUUAACCUGGUGCUG 12057 cuAccuuAAccuGGuGcuGdTsdT sense
    1903-1922 10058 CAGCACCAGGUUAAGGUAG 12058 cAGcACcAGGUuAAGGuAGdTsdT antis
    1911-1930 10059 ACCUGGUGCUGGACUAUGU 12059 AccuGGuGcuGGAcuAuGudTsdT sense
    1911-1930 10060 ACAUAGUCCAGCACCAGGU 12060 AcAuAGUCcAGcACcAGGUdTsdT antis
    1912-1931 10061 CCUGGUGCUGGACUAUGUU 12061 ccuGGuGcuGGAcuAuGuudTsdT sense
    1912-1931 10062 AACAUAGUCCAGCACCAGG 12062 AAcAuAGUCcAGcACcAGGdTsdT antis
    1915-1934 10063 GGUGCUGGACUAUGUUCCG 12063 GGuGcuGGAcuAuGuuccGdTsdT sense
    1915-1934 10064 CGGAACAUAGUCCAGCACC 12064 CGGAAcAuAGUCcAGcACCdTsdT antis
    1929-1948 10065 UUCCGGAGACAGUGUACAG 12065 uuccGGAGAcAGuGuAcAGdTsdT sense
    1929-1948 10066 CUGUACACUGUCUCCGGAA 12066 CUGuAcACUGUCUCCGGAAdTsdT antis
    1933-1952 10067 GGAGACAGUGUACAGAGUC 12067 GGAGAcAGuGuAcAGAGucdTsdT sense
    1933-1952 10068 GACUCUGUACACUGUCUCC 12068 GACUCUGuAcACUGUCUCCdTsdT antis
    1935-1954 10069 AGACAGUGUACAGAGUCGC 12069 AGAcAGuGuAcAGAGucGcdTsdT sense
    1935-1954 10070 GCGACUCUGUACACUGUCU 12070 GCGACUCUGuAcACUGUCUdTsdT antis
    1941-1960 10071 UGUACAGAGUCGCCAGACA 12071 uGuAcAGAGucGccAGAcAdTsdT sense
    1941-1960 10072 UGUCUGGCGACUCUGUACA 12072 UGUCUGGCGACUCUGuAcAdTsdT antis
    1944-1963 10073 ACAGAGUCGCCAGACACUA 12073 AcAGAGucGccAGAcAcuAdTsdT sense
    1944-1963 10074 UAGUGUCUGGCGACUCUGU 12074 uAGUGUCUGGCGACUCUGUdTsdT antis
    1945-1964 10075 CAGAGUCGCCAGACACUAU 12075 cAGAGucGccAGAcAcuAudTsdT sense
    1945-1964 10076 AUAGUGUCUGGCGACUCUG 12076 AuAGUGUCUGGCGACUCUGdTsdT antis
    1965-1984 10077 GUCGAGCCAAGCAGACACU 12077 GucGAGccAAGcAGAcAcudTsdT sense
    1965-1984 10078 AGUGUCUGCUUGGCUCGAC 12078 AGUGUCUGCUUGGCUCGACdTsdT antis
    1966-1985 10079 UCGAGCCAAGCAGACACUC 12079 ucGAGccAAGcAGAcAcucdTsdT sense
    1966-1985 10080 GAGUGUCUGCUUGGCUCGA 12080 GAGUGUCUGCUUGGCUCGAdTsdT antis
    1967-1986 10081 CGAGCCAAGCAGACACUCC 12081 cGAGccAAGcAGAcAcuccdTsdT sense
    1967-1986 10082 GGAGUGUCUGCUUGGCUCG 12082 GGAGUGUCUGCUUGGCUCGdTsdT antis
    1970-1989 10083 GCCAAGCAGACACUCCCUG 12083 GccAAGcAGAcAcucccuGdTsdT sense
    1970-1989 10084 CAGGGAGUGUCUGCUUGGC 12084 cAGGGAGUGUCUGCUUGGCdTsdT antis
    1971-1990 10085 CCAAGCAGACACUCCCUGU 12085 ccAAGcAGAcAcucccuGudTsdT sense
    1971-1990 10086 ACAGGGAGUGUCUGCUUGG 12086 AcAGGGAGUGUCUGCUUGGdTsdT antis
    1974-1993 10087 AGCAGACACUCCCUGUGAU 12087 AGcAGAcAcucccuGuGAudTsdT sense
    1974-1993 10088 AUCACAGGGAGUGUCUGCU 12088 AUcAcAGGGAGUGUCUGCUdTsdT antis
    1975-1994 10089 GCAGACACUCCCUGUGAUC 12089 GcAGAcAcucccuGuGAucdTsdT sense
    1975-1994 10090 GAUCACAGGGAGUGUCUGC 12090 GAUcAcAGGGAGUGUCUGCdTsdT antis
    1986-2005 10091 CUGUGAUCUAUGUCAAGUU 12091 cuGuGAucuAuGucAAGuudTsdT sense
    1986-2005 10092 AACUUGACAUAGAUCACAG 12092 AACUUGAcAuAGAUcAcAGdTsdT antis
    1993-2012 10093 CUAUGUCAAGUUGUAUAUG 12093 cuAuGucAAGuuGuAuAuGdTsdT sense
    1993-2012 10094 CAUAUACAACUUGACAUAG 12094 cAuAuAcAACUUGAcAuAGdTsdT antis
    1995-2014 10095 AUGUCAAGUUGUAUAUGUA 12095 AuGucAAGuuGuAuAuGuAdTsdT sense
    1995-2014 10096 UACAUAUACAACUUGACAU 12096 uAcAuAuAcAACUUGAcAUdTsdT antis
    1996-2015 10097 UGUCAAGUUGUAUAUGUAU 12097 uGucAAGuuGuAuAuGuAudTsdT sense
    1996-2015 10098 AUACAUAUACAACUUGACA 12098 AuAcAuAuAcAACUUGAcAdTsdT antis
    1999-2018 10099 CAAGUUGUAUAUGUAUCAG 12099 cAAGuuGuAuAuGuAucAGdTsdT sense
    1999-2018 10100 CUGAUACAUAUACAACUUG 12100 CUGAuAcAuAuAcAACUUGdTsdT antis
    2009-2028 10101 AUGUAUCAGCUGUUCAGAA 12101 AuGuAucAGcuGuucAGAAdTsdT sense
    2009-2028 10102 UUCUGAACAGCUGAUACAU 12102 UUCUGAAcAGCUGAuAcAUdTsdT antis
    2010-2029 10103 UGUAUCAGCUGUUCAGAAG 12103 uGuAucAGcuGuucAGAAGdTsdT sense
    2010-2029 10104 CUUCUGAACAGCUGAUACA 12104 CUUCUGAAcAGCUGAuAcAdTsdT antis
    2016-2035 10105 AGCUGUUCAGAAGUCUAGC 12105 AGcuGuucAGAAGucuAGcdTsdT sense
    2016-2035 10106 GCUAGACUUCUGAACAGCU 12106 GCuAGACUUCUGAAcAGCUdTsdT antis
    2035-2054 10107 CUAUAUCCAUUCCUUUGGA 12107 cuAuAuccAuuccuuuGGAdTsdT sense
    2035-2054 10108 UCCAAAGGAAUGGAUAUAG 12108 UCcAAAGGAAUGGAuAuAGdTsdT antis
    2036-2055 10109 UAUAUCCAUUCCUUUGGAA 12109 uAuAuccAuuccuuuGGAAdTsdT sense
    2036-2055 10110 UUCCAAAGGAAUGGAUAUA 12110 UUCcAAAGGAAUGGAuAuAdTsdT antis
    2046-2065 10111 CCUUUGGAAUCUGCCAUCG 12111 ccuuuGGAAucuGccAucGdTsdT sense
    2046-2065 10112 CGAUGGCAGAUUCCAAAGG 12112 CGAUGGcAGAUUCcAAAGGdTsdT antis
    2049-2068 10113 UUGGAAUCUGCCAUCGAGA 12113 uuGGAAucuGccAucGAGAdTsdT sense
    2049-2068 10114 UCUCGAUGGCAGAUUCCAA 12114 UCUCGAUGGcAGAUUCcAAdTsdT antis
    2051-2070 10115 GGAAUCUGCCAUCGAGACA 12115 GGAAucuGccAucGAGAcAdTsdT sense
    2051-2070 10116 UGUCUCGAUGGCAGAUUCC 12116 UGUCUCGAUGGcAGAUUCCdTsdT antis
    2068-2087 10117 CAUUAAACCACAGAACCUC 12117 cAuuAAAccAcAGAAccucdTsdT sense
    2068-2087 10118 GAGGUUCUGUGGUUUAAUG 12118 GAGGUUCUGUGGUUuAAUGdTsdT antis
    2070-2089 10119 UUAAACCACAGAACCUCUU 12119 uuAAAccAcAGAAccucuudTsdT sense
    2070-2089 10120 AAGAGGUUCUGUGGUUUAA 12120 AAGAGGUUCUGUGGUUuAAdTsdT antis
    2071-2090 10121 UAAACCACAGAACCUCUUG 12121 uAAAccAcAGAAccucuuGdTsdT sense
    2071-2090 10122 CAAGAGGUUCUGUGGUUUA 12122 cAAGAGGUUCUGUGGUUuAdTsdT antis
    2073-2092 10123 AACCACAGAACCUCUUGUU 12123 AAccAcAGAAccucuuGuudTsdT sense
    2073-2092 10124 AACAAGAGGUUCUGUGGUU 12124 AAcAAGAGGUUCUGUGGUUdTsdT antis
    2075-2094 10125 CCACAGAACCUCUUGUUGG 12125 ccAcAGAAccucuuGuuGGdTsdT sense
    2075-2094 10126 CCAACAAGAGGUUCUGUGG 12126 CcAAcAAGAGGUUCUGUGGdTsdT antis
    2076-2095 10127 CACAGAACCUCUUGUUGGA 12127 cAcAGAAccucuuGuuGGAdTsdT sense
    2076-2095 10128 UCCAACAAGAGGUUCUGUG 12128 UCcAAcAAGAGGUUCUGUGdTsdT antis
    2078-2097 10129 CAGAACCUCUUGUUGGAUC 12129 cAGAAccucuuGuuGGAucdTsdT sense
    2078-2097 10130 GAUCCAACAAGAGGUUCUG 12130 GAUCcAAcAAGAGGUUCUGdTsdT antis
    2084-2103 10131 CUCUUGUUGGAUCCUGAUA 12131 cucuuGuuGGAuccuGAuAdTsdT sense
    2084-2103 10132 UAUCAGGAUCCAACAAGAG 12132 uAUcAGGAUCcAAcAAGAGdTsdT antis
    2086-2105 10133 CUUGUUGGAUCCUGAUACA 12133 cuuGuuGGAuccuGAuAcAdTsdT sense
    2086-2105 10134 UGUAUCAGGAUCCAACAAG 12134 UGuAUcAGGAUCcAAcAAGdTsdT antis
    2095-2114 10135 UCCUGAUACAGCUGUAUUA 12135 uccuGAuAcAGcuGuAuuAdTsdT sense
    2095-2114 10136 UAAUACAGCUGUAUCAGGA 12136 uAAuAcAGCUGuAUcAGGAdTsdT antis
    2102-2121 10137 ACAGCUGUAUUAAAACUCU 12137 AcAGcuGuAuuAAAAcucudTsdT sense
    2102-2121 10138 AGAGUUUUAAUACAGCUGU 12138 AGAGUUUuAAuAcAGCUGUdTsdT antis
    2103-2122 10139 CAGCUGUAUUAAAACUCUG 12139 cAGcuGuAuuAAAAcucuGdTsdT sense
    2103-2122 10140 CAGAGUUUUAAUACAGCUG 12140 cAGAGUUUuAAuAcAGCUGdTsdT antis
    2105-2124 10141 GCUGUAUUAAAACUCUGUG 12141 GcuGuAuuAAAAcucuGuGdTsdT sense
    2105-2124 10142 CACAGAGUUUUAAUACAGC 12142 cAcAGAGUUUuAAuAcAGCdTsdT antis
    2106-2125 10143 CUGUAUUAAAACUCUGUGA 12143 cuGuAuuAAAAcucuGuGAdTsdT sense
    2106-2125 10144 UCACAGAGUUUUAAUACAG 12144 UcAcAGAGUUUuAAuAcAGdTsdT antis
    2108-2127 10145 GUAUUAAAACUCUGUGACU 12145 GuAuuAAAAcucuGuGAcudTsdT sense
    2108-2127 10146 AGUCACAGAGUUUUAAUAC 12146 AGUcAcAGAGUUUuAAuACdTsdT antis
    2115-2134 10147 AACUCUGUGACUUUGGAAG 12147 AAcucuGuGAcuuuGGAAGdTsdT sense
    2115-2134 10148 CUUCCAAAGUCACAGAGUU 12148 CUUCcAAAGUcAcAGAGUUdTsdT antis
    2120-2139 10149 UGUGACUUUGGAAGUGCAA 12149 uGuGAcuuuGGAAGuGcAAdTsdT sense
    2120-2139 10150 UUGCACUUCCAAAGUCACA 12150 UUGcACUUCcAAAGUcAcAdTsdT antis
    2124-2143 10151 ACUUUGGAAGUGCAAAGCA 12151 AcuuuGGAAGuGcAAAGcAdTsdT sense
    2124-2143 10152 UGCUUUGCACUUCCAAAGU 12152 UGCUUUGcACUUCcAAAGUdTsdT antis
    2132-2151 10153 AGUGCAAAGCAGCUGGUCC 12153 AGuGcAAAGcAGcuGGuccdTsdT sense
    2132-2151 10154 GGACCAGCUGCUUUGCACU 12154 GGACcAGCUGCUUUGcACUdTsdT antis
    2134-2153 10155 UGCAAAGCAGCUGGUCCGA 12155 uGcAAAGcAGcuGGuccGAdTsdT sense
    2134-2153 10156 UCGGACCAGCUGCUUUGCA 12156 UCGGACcAGCUGCUUUGcAdTsdT antis
    2136-2155 10157 CAAAGCAGCUGGUCCGAGG 12157 cAAAGcAGcuGGuccGAGGdTsdT sense
    2136-2155 10158 CCUCGGACCAGCUGCUUUG 12158 CCUCGGACcAGCUGCUUUGdTsdT antis
    2139-2158 10159 AGCAGCUGGUCCGAGGAGA 12159 AGcAGcuGGuccGAGGAGAdTsdT sense
    2139-2158 10160 UCUCCUCGGACCAGCUGCU 12160 UCUCCUCGGACcAGCUGCUdTsdT antis
    2140-2159 10161 GCAGCUGGUCCGAGGAGAG 12161 GcAGcuGGuccGAGGAGAGdTsdT sense
    2140-2159 10162 CUCUCCUCGGACCAGCUGC 12162 CUCUCCUCGGACcAGCUGCdTsdT antis
    2141-2160 10163 CAGCUGGUCCGAGGAGAGC 12163 cAGcuGGuccGAGGAGAGcdTsdT sense
    2141-2160 10164 GCUCUCCUCGGACCAGCUG 12164 GCUCUCCUCGGACcAGCUGdTsdT antis
    2142-2161 10165 AGCUGGUCCGAGGAGAGCC 12165 AGcuGGuccGAGGAGAGccdTsdT sense
    2142-2161 10166 GGCUCUCCUCGGACCAGCU 12166 GGCUCUCCUCGGACcAGCUdTsdT antis
    2146-2165 10167 GGUCCGAGGAGAGCCCAAU 12167 GGuccGAGGAGAGcccAAudTsdT sense
    2146-2165 10168 AUUGGGCUCUCCUCGGACC 12168 AUUGGGCUCUCCUCGGACCdTsdT antis
    2147-2166 10169 GUCCGAGGAGAGCCCAAUG 12169 GuccGAGGAGAGcccAAuGdTsdT sense
    2147-2166 10170 CAUUGGGCUCUCCUCGGAC 12170 cAUUGGGCUCUCCUCGGACdTsdT antis
    2160-2179 10171 CCAAUGUUUCAUAUAUCUG 12171 ccAAuGuuucAuAuAucuGdTsdT sense
    2160-2179 10172 CAGAUAUAUGAAACAUUGG 12172 cAGAuAuAUGAAAcAUUGGdTsdT antis
    2189-2208 10173 UACAGGGCACCAGAGUUGA 12173 uAcAGGGcAccAGAGuuGAdTsdT sense
    2189-2208 10174 UCAACUCUGGUGCCCUGUA 12174 UcAACUCUGGUGCCCUGuAdTsdT antis
    2191-2210 10175 CAGGGCACCAGAGUUGAUC 12175 cAGGGcAccAGAGuuGAucdTsdT sense
    2191-2210 10176 GAUCAACUCUGGUGCCCUG 12176 GAUcAACUCUGGUGCCCUGdTsdT antis
    2194-2213 10177 GGCACCAGAGUUGAUCUUU 12177 GGcAccAGAGuuGAucuuudTsdT sense
    2194-2213 10178 AAAGAUCAACUCUGGUGCC 12178 AAAGAUcAACUCUGGUGCCdTsdT antis
    2195-2214 10179 GCACCAGAGUUGAUCUUUG 12179 GcAccAGAGuuGAucuuuGdTsdT sense
    2195-2214 10180 CAAAGAUCAACUCUGGUGC 12180 cAAAGAUcAACUCUGGUGCdTsdT antis
    2196-2215 10181 CACCAGAGUUGAUCUUUGG 12181 cAccAGAGuuGAucuuuGGdTsdT sense
    2196-2215 10182 CCAAAGAUCAACUCUGGUG 12182 CcAAAGAUcAACUCUGGUGdTsdT antis
    2201-2220 10183 GAGUUGAUCUUUGGAGCCA 12183 GAGuuGAucuuuGGAGccAdTsdT sense
    2201-2220 10184 UGGCUCCAAAGAUCAACUC 12184 UGGCUCcAAAGAUcAACUCdTsdT antis
    2211-2230 10185 UUGGAGCCACUGAUUACAC 12185 uuGGAGccAcuGAuuAcAcdTsdT sense
    2211-2230 10186 GUGUAAUCAGUGGCUCCAA 12186 GUGuAAUcAGUGGCUCcAAdTsdT antis
    2234-2253 10187 AGUAUAGAUGUAUGGUCUG 12187 AGuAuAGAuGuAuGGucuGdTsdT sense
    2234-2253 10188 CAGACCAUACAUCUAUACU 12188 cAGACcAuAcAUCuAuACUdTsdT antis
    2238-2257 10189 UAGAUGUAUGGUCUGCAGG 12189 uAGAuGuAuGGucuGcAGGdTsdT sense
    2238-2257 10190 CCUGCAGACCAUACAUCUA 12190 CCUGcAGACcAuAcAUCuAdTsdT antis
    2240-2259 10191 GAUGUAUGGUCUGCAGGCU 12191 GAuGuAuGGucuGcAGGcudTsdT sense
    2240-2259 10192 AGCCUGCAGACCAUACAUC 12192 AGCCUGcAGACcAuAcAUCdTsdT antis
    2241-2260 10193 AUGUAUGGUCUGCAGGCUG 12193 AuGuAuGGucuGcAGGcuGdTsdT sense
    2241-2260 10194 CAGCCUGCAGACCAUACAU 12194 cAGCCUGcAGACcAuAcAUdTsdT antis
    2242-2261 10195 UGUAUGGUCUGCAGGCUGU 12195 uGuAuGGucuGcAGGcuGudTsdT sense
    2242-2261 10196 ACAGCCUGCAGACCAUACA 12196 AcAGCCUGcAGACcAuAcAdTsdT antis
    2249-2268 10197 UCUGCAGGCUGUGUGUUGG 12197 ucuGcAGGcuGuGuGuuGGdTsdT sense
    2249-2268 10198 CCAACACACAGCCUGCAGA 12198 CcAAcAcAcAGCCUGcAGAdTsdT antis
    2255-2274 10199 GGCUGUGUGUUGGCUGAAU 12199 GGcuGuGuGuuGGcuGAAudTsdT sense
    2255-2274 10200 AUUCAGCCAACACACAGCC 12200 AUUcAGCcAAcAcAcAGCCdTsdT antis
    2256-2275 10201 GCUGUGUGUUGGCUGAAUU 12201 GcuGuGuGuuGGcuGAAuudTsdT sense
    2256-2275 10202 AAUUCAGCCAACACACAGC 12202 AAUUcAGCcAAcAcAcAGCdTsdT antis
    2257-2276 10203 CUGUGUGUUGGCUGAAUUG 12203 cuGuGuGuuGGcuGAAuuGdTsdT sense
    2257-2276 10204 CAAUUCAGCCAACACACAG 12204 cAAUUcAGCcAAcAcAcAGdTsdT antis
    2259-2278 10205 GUGUGUUGGCUGAAUUGUU 12205 GuGuGuuGGcuGAAuuGuudTsdT sense
    2259-2278 10206 AACAAUUCAGCCAACACAC 12206 AAcAAUUcAGCcAAcAcACdTsdT antis
    2260-2279 10207 UGUGUUGGCUGAAUUGUUG 12207 uGuGuuGGcuGAAuuGuuGdTsdT sense
    2260-2279 10208 CAACAAUUCAGCCAACACA 12208 cAAcAAUUcAGCcAAcAcAdTsdT antis
    2271-2290 10209 AAUUGUUGCUAGGACAACC 12209 AAuuGuuGcuAGGAcAAccdTsdT sense
    2271-2290 10210 GGUUGUCCUAGCAACAAUU 12210 GGUUGUCCuAGcAAcAAUUdTsdT antis
    2280-2299 10211 UAGGACAACCAAUAUUUCC 12211 uAGGAcAAccAAuAuuuccdTsdT sense
    2280-2299 10212 GGAAAUAUUGGUUGUCCUA 12212 GGAAAuAUUGGUUGUCCuAdTsdT antis
    2284-2303 10213 ACAACCAAUAUUUCCUGGG 12213 AcAAccAAuAuuuccuGGGdTsdT sense
    2284-2303 10214 CCCAGGAAAUAUUGGUUGU 12214 CCcAGGAAAuAUUGGUUGUdTsdT antis
    2287-2306 10215 ACCAAUAUUUCCUGGGGAC 12215 AccAAuAuuuccuGGGGAcdTsdT sense
    2287-2306 10216 GUCCCCAGGAAAUAUUGGU 12216 GUCCCcAGGAAAuAUUGGUdTsdT antis
    2288-2307 10217 CCAAUAUUUCCUGGGGACA 12217 ccAAuAuuuccuGGGGAcAdTsdT sense
    2288-2307 10218 UGUCCCCAGGAAAUAUUGG 12218 UGUCCCcAGGAAAuAUUGGdTsdT antis
    2289-2308 10219 CAAUAUUUCCUGGGGACAG 12219 cAAuAuuuccuGGGGAcAGdTsdT sense
    2289-2308 10220 CUGUCCCCAGGAAAUAUUG 12220 CUGUCCCcAGGAAAuAUUGdTsdT antis
    2290-2309 10221 AAUAUUUCCUGGGGACAGU 12221 AAuAuuuccuGGGGAcAGudTsdT sense
    2290-2309 10222 ACUGUCCCCAGGAAAUAUU 12222 ACUGUCCCcAGGAAAuAUUdTsdT antis
    2292-2311 10223 UAUUUCCUGGGGACAGUGG 12223 uAuuuccuGGGGAcAGuGGdTsdT sense
    2292-2311 10224 CCACUGUCCCCAGGAAAUA 12224 CcACUGUCCCcAGGAAAuAdTsdT antis
    2299-2318 10225 UGGGGACAGUGGUGUGGAU 12225 uGGGGAcAGuGGuGuGGAudTsdT sense
    2299-2318 10226 AUCCACACCACUGUCCCCA 12226 AUCcAcACcACUGUCCCcAdTsdT antis
    2303-2322 10227 GACAGUGGUGUGGAUCAGU 12227 GAcAGuGGuGuGGAucAGudTsdT sense
    2303-2322 10228 ACUGAUCCACACCACUGUC 12228 ACUGAUCcAcACcACUGUCdTsdT antis
    2310-2329 10229 GUGUGGAUCAGUUGGUGGA 12229 GuGuGGAucAGuuGGuGGAdTsdT sense
    2310-2329 10230 UCCACCAACUGAUCCACAC 12230 UCcACcAACUGAUCcAcACdTsdT antis
    2316-2335 10231 AUCAGUUGGUGGAAAUAAU 12231 AucAGuuGGuGGAAAuAAudTsdT sense
    2316-2335 10232 AUUAUUUCCACCAACUGAU 12232 AUuAUUUCcACcAACUGAUdTsdT antis
    2324-2343 10233 GUGGAAAUAAUAAAGGUCC 12233 GuGGAAAuAAuAAAGGuccdTsdT sense
    2324-2343 10234 GGACCUUUAUUAUUUCCAC 12234 GGACCUUuAUuAUUUCcACdTsdT antis
    2327-2346 10235 GAAAUAAUAAAGGUCCUAG 12235 GAAAuAAuAAAGGuccuAGdTsdT sense
    2327-2346 10236 CUAGGACCUUUAUUAUUUC 12236 CuAGGACCUUuAUuAUUUCdTsdT antis
    2333-2352 10237 AUAAAGGUCCUAGGAACAC 12237 AuAAAGGuccuAGGAAcAcdTsdT sense
    2333-2352 10238 GUGUUCCUAGGACCUUUAU 12238 GUGUUCCuAGGACCUUuAUdTsdT antis
    2335-2354 10239 AAAGGUCCUAGGAACACCA 12239 AAAGGuccuAGGAAcAccAdTsdT sense
    2335-2354 10240 UGGUGUUCCUAGGACCUUU 12240 UGGUGUUCCuAGGACCUUUdTsdT antis
    2341-2360 10241 CCUAGGAACACCAACAAGG 12241 ccuAGGAAcAccAAcAAGGdTsdT sense
    2341-2360 10242 CCUUGUUGGUGUUCCUAGG 12242 CCUUGUUGGUGUUCCuAGGdTsdT antis
    2345-2364 10243 GGAACACCAACAAGGGAGC 12243 GGAAcAccAAcAAGGGAGcdTsdT sense
    2345-2364 10244 GCUCCCUUGUUGGUGUUCC 12244 GCUCCCUUGUUGGUGUUCCdTsdT antis
    2356-2375 10245 AAGGGAGCAAAUUAGAGAA 12245 AAGGGAGcAAAuuAGAGAAdTsdT sense
    2356-2375 10246 UUCUCUAAUUUGCUCCCUU 12246 UUCUCuAAUUUGCUCCCUUdTsdT antis
    2358-2377 10247 GGGAGCAAAUUAGAGAAAU 12247 GGGAGcAAAuuAGAGAAAudTsdT sense
    2358-2377 10248 AUUUCUCUAAUUUGCUCCC 12248 AUUUCUCuAAUUUGCUCCCdTsdT antis
    2364-2383 10249 AAAUUAGAGAAAUGAACCC 12249 AAAuuAGAGAAAuGAAcccdTsdT sense
    2364-2383 10250 GGGUUCAUUUCUCUAAUUU 12250 GGGUUcAUUUCUCuAAUUUdTsdT antis
    2365-2384 10251 AAUUAGAGAAAUGAACCCA 12251 AAuuAGAGAAAuGAAcccAdTsdT sense
    2365-2384 10252 UGGGUUCAUUUCUCUAAUU 12252 UGGGUUcAUUUCUCuAAUUdTsdT antis
    2368-2387 10253 UAGAGAAAUGAACCCAAAU 12253 uAGAGAAAuGAAcccAAAudTsdT sense
    2368-2387 10254 AUUUGGGUUCAUUUCUCUA 12254 AUUUGGGUUcAUUUCUCuAdTsdT antis
    2369-2388 10255 AGAGAAAUGAACCCAAAUU 12255 AGAGAAAuGAAcccAAAuudTsdT sense
    2369-2388 10256 AAUUUGGGUUCAUUUCUCU 12256 AAUUUGGGUUcAUUUCUCUdTsdT antis
    2371-2390 10257 AGAAAUGAACCCAAAUUAU 12257 AGAAAuGAAcccAAAuuAudTsdT sense
    2371-2390 10258 AUAAUUUGGGUUCAUUUCU 12258 AuAAUUUGGGUUcAUUUCUdTsdT antis
    2372-2391 10259 GAAAUGAACCCAAAUUAUA 12259 GAAAuGAAcccAAAuuAuAdTsdT sense
    2372-2391 10260 UAUAAUUUGGGUUCAUUUC 12260 uAuAAUUUGGGUUcAUUUCdTsdT antis
    2374-2393 10261 AAUGAACCCAAAUUAUACA 12261 AAuGAAcccAAAuuAuAcAdTsdT sense
    2374-2393 10262 UGUAUAAUUUGGGUUCAUU 12262 UGuAuAAUUUGGGUUcAUUdTsdT antis
    2375-2394 10263 AUGAACCCAAAUUAUACAG 12263 AuGAAcccAAAuuAuAcAGdTsdT sense
    2375-2394 10264 CUGUAUAAUUUGGGUUCAU 12264 CUGuAuAAUUUGGGUUcAUdTsdT antis
    2381-2400 10265 CCAAAUUAUACAGAAUUCA 12265 ccAAAuuAuAcAGAAuucAdTsdT sense
    2381-2400 10266 UGAAUUCUGUAUAAUUUGG 12266 UGAAUUCUGuAuAAUUUGGdTsdT antis
    2386-2405 10267 UUAUACAGAAUUCAAAUUC 12267 uuAuAcAGAAuucAAAuucdTsdT sense
    2386-2405 10268 GAAUUUGAAUUCUGUAUAA 12268 GAAUUUGAAUUCUGuAuAAdTsdT antis
    2387-2406 10269 UAUACAGAAUUCAAAUUCC 12269 uAuAcAGAAuucAAAuuccdTsdT sense
    2387-2406 10270 GGAAUUUGAAUUCUGUAUA 12270 GGAAUUUGAAUUCUGuAuAdTsdT antis
    2388-2407 10271 AUACAGAAUUCAAAUUCCC 12271 AuAcAGAAuucAAAuucccdTsdT sense
    2388-2407 10272 GGGAAUUUGAAUUCUGUAU 12272 GGGAAUUUGAAUUCUGuAUdTsdT antis
    2396-2415 10273 UUCAAAUUCCCUCAAAUCA 12273 uucAAAuucccucAAAucAdTsdT sense
    2396-2415 10274 UGAUUUGAGGGAAUUUGAA 12274 UGAUUUGAGGGAAUUUGAAdTsdT antis
    2398-2417 10275 CAAAUUCCCUCAAAUCAAG 12275 cAAAuucccucAAAucAAGdTsdT sense
    2398-2417 10276 CUUGAUUUGAGGGAAUUUG 12276 CUUGAUUUGAGGGAAUUUGdTsdT antis
    2399-2418 10277 AAAUUCCCUCAAAUCAAGG 12277 AAAuucccucAAAucAAGGdTsdT sense
    2399-2418 10278 CCUUGAUUUGAGGGAAUUU 12278 CCUUGAUUUGAGGGAAUUUdTsdT antis
    2406-2425 10279 CUCAAAUCAAGGCACAUCC 12279 cucAAAucAAGGcAcAuccdTsdT sense
    2406-2425 10280 GGAUGUGCCUUGAUUUGAG 12280 GGAUGUGCCUUGAUUUGAGdTsdT antis
    2407-2426 10281 UCAAAUCAAGGCACAUCCU 12281 ucAAAucAAGGcAcAuccudTsdT sense
    2407-2426 10282 AGGAUGUGCCUUGAUUUGA 12282 AGGAUGUGCCUUGAUUUGAdTsdT antis
    2410-2429 10283 AAUCAAGGCACAUCCUUGG 12283 AAucAAGGcAcAuccuuGGdTsdT sense
    2410-2429 10284 CCAAGGAUGUGCCUUGAUU 12284 CcAAGGAUGUGCCUUGAUUdTsdT antis
    2411-2430 10285 AUCAAGGCACAUCCUUGGA 12285 AucAAGGcAcAuccuuGGAdTsdT sense
    2411-2430 10286 UCCAAGGAUGUGCCUUGAU 12286 UCcAAGGAUGUGCCUUGAUdTsdT antis
    2413-2432 10287 CAAGGCACAUCCUUGGACA 12287 cAAGGcAcAuccuuGGAcAdTsdT sense
    2413-2432 10288 UGUCCAAGGAUGUGCCUUG 12288 UGUCcAAGGAUGUGCCUUGdTsdT antis
    2415-2434 10289 AGGCACAUCCUUGGACAAA 12289 AGGcAcAuccuuGGAcAAAdTsdT sense
    2415-2434 10290 UUUGUCCAAGGAUGUGCCU 12290 UUUGUCcAAGGAUGUGCCUdTsdT antis
    2416-2435 10291 GGCACAUCCUUGGACAAAG 12291 GGcAcAuccuuGGAcAAAGdTsdT sense
    2416-2435 10292 CUUUGUCCAAGGAUGUGCC 12292 CUUUGUCcAAGGAUGUGCCdTsdT antis
    2417-2436 10293 GCACAUCCUUGGACAAAGG 12293 GcAcAuccuuGGAcAAAGGdTsdT sense
    2417-2436 10294 CCUUUGUCCAAGGAUGUGC 12294 CCUUUGUCcAAGGAUGUGCdTsdT antis
    2418-2437 10295 CACAUCCUUGGACAAAGGU 12295 cAcAuccuuGGAcAAAGGudTsdT sense
    2418-2437 10296 ACCUUUGUCCAAGGAUGUG 12296 ACCUUUGUCcAAGGAUGUGdTsdT antis
    2420-2439 10297 CAUCCUUGGACAAAGGUCU 12297 cAuccuuGGAcAAAGGucudTsdT sense
    2420-2439 10298 AGACCUUUGUCCAAGGAUG 12298 AGACCUUUGUCcAAGGAUGdTsdT antis
    2422-2441 10299 UCCUUGGACAAAGGUCUUC 12299 uccuuGGAcAAAGGucuucdTsdT sense
    2422-2441 10300 GAAGACCUUUGUCCAAGGA 12300 GAAGACCUUUGUCcAAGGAdTsdT antis
    2426-2445 10301 UGGACAAAGGUCUUCCGGC 12301 uGGAcAAAGGucuuccGGcdTsdT sense
    2426-2445 10302 GCCGGAAGACCUUUGUCCA 12302 GCCGGAAGACCUUUGUCcAdTsdT antis
    2430-2449 10303 CAAAGGUCUUCCGGCCCCG 12303 cAAAGGucuuccGGccccGdTsdT sense
    2430-2449 10304 CGGGGCCGGAAGACCUUUG 12304 CGGGGCCGGAAGACCUUUGdTsdT antis
    2439-2458 10305 UCCGGCCCCGAACUCCACC 12305 uccGGccccGAAcuccAccdTsdT sense
    2439-2458 10306 GGUGGAGUUCGGGGCCGGA 12306 GGUGGAGUUCGGGGCCGGAdTsdT antis
    2443-2462 10307 GCCCCGAACUCCACCAGAG 12307 GccccGAAcuccAccAGAGdTsdT sense
    2443-2462 10308 CUCUGGUGGAGUUCGGGGC 12308 CUCUGGUGGAGUUCGGGGCdTsdT antis
    2444-2463 10309 CCCCGAACUCCACCAGAGG 12309 ccccGAAcuccAccAGAGGdTsdT sense
    2444-2463 10310 CCUCUGGUGGAGUUCGGGG 12310 CCUCUGGUGGAGUUCGGGGdTsdT antis
    2446-2465 10311 CCGAACUCCACCAGAGGCA 12311 ccGAAcuccAccAGAGGcAdTsdT sense
    2446-2465 10312 UGCCUCUGGUGGAGUUCGG 12312 UGCCUCUGGUGGAGUUCGGdTsdT antis
    2447-2466 10313 CGAACUCCACCAGAGGCAA 12313 cGAAcuccAccAGAGGcAAdTsdT sense
    2447-2466 10314 UUGCCUCUGGUGGAGUUCG 12314 UUGCCUCUGGUGGAGUUCGdTsdT antis
    2448-2467 10315 GAACUCCACCAGAGGCAAU 12315 GAAcuccAccAGAGGcAAudTsdT sense
    2448-2467 10316 AUUGCCUCUGGUGGAGUUC 12316 AUUGCCUCUGGUGGAGUUCdTsdT antis
    2458-2477 10317 AGAGGCAAUUGCACUGUGC 12317 AGAGGcAAuuGcAcuGuGcdTsdT sense
    2458-2477 10318 GCACAGUGCAAUUGCCUCU 12318 GcAcAGUGcAAUUGCCUCUdTsdT antis
    2459-2478 10319 GAGGCAAUUGCACUGUGCA 12319 GAGGcAAuuGcAcuGuGcAdTsdT sense
    2459-2478 10320 UGCACAGUGCAAUUGCCUC 12320 UGcAcAGUGcAAUUGCCUCdTsdT antis
    2461-2480 10321 GGCAAUUGCACUGUGCAGC 12321 GGcAAuuGcAcuGuGcAGcdTsdT sense
    2461-2480 10322 GCUGCACAGUGCAAUUGCC 12322 GCUGcAcAGUGcAAUUGCCdTsdT antis
    2462-2481 10323 GCAAUUGCACUGUGCAGCC 12323 GcAAuuGcAcuGuGcAGccdTsdT sense
    2462-2481 10324 GGCUGCACAGUGCAAUUGC 12324 GGCUGcAcAGUGcAAUUGCdTsdT antis
    2464-2483 10325 AAUUGCACUGUGCAGCCGU 12325 AAuuGcAcuGuGcAGccGudTsdT sense
    2464-2483 10326 ACGGCUGCACAGUGCAAUU 12326 ACGGCUGcAcAGUGcAAUUdTsdT antis
    2465-2484 10327 AUUGCACUGUGCAGCCGUC 12327 AuuGcAcuGuGcAGccGucdTsdT sense
    2465-2484 10328 GACGGCUGCACAGUGCAAU 12328 GACGGCUGcAcAGUGcAAUdTsdT antis
    2471-2490 10329 CUGUGCAGCCGUCUGCUGG 12329 cuGuGcAGccGucuGcuGGdTsdT sense
    2471-2490 10330 CCAGCAGACGGCUGCACAG 12330 CcAGcAGACGGCUGcAcAGdTsdT antis
    2485-2504 10331 GCUGGAGUACACACCUACC 12331 GcuGGAGuAcAcAccuAccdTsdT sense
    2485-2504 10332 GGUAGGUGUGUACUCCAGC 12332 GGuAGGUGUGuACUCcAGCdTsdT antis
    2507-2526 10333 CGGCUAACACCACUGGAAG 12333 cGGcuAAcAccAcuGGAAGdTsdT sense
    2507-2526 10334 CUUCCAGUGGUGUUAGCCG 12334 CUUCcAGUGGUGUuAGCCGdTsdT antis
    2509-2528 10335 GCUAACACCACUGGAAGCU 12335 GcuAAcAccAcuGGAAGcudTsdT sense
    2509-2528 10336 AGCUUCCAGUGGUGUUAGC 12336 AGCUUCcAGUGGUGUuAGCdTsdT antis
    2510-2529 10337 CUAACACCACUGGAAGCUU 12337 cuAAcAccAcuGGAAGcuudTsdT sense
    2510-2529 10338 AAGCUUCCAGUGGUGUUAG 12338 AAGCUUCcAGUGGUGUuAGdTsdT antis
    2512-2531 10339 AACACCACUGGAAGCUUGU 12339 AAcAccAcuGGAAGcuuGudTsdT sense
    2512-2531 10340 ACAAGCUUCCAGUGGUGUU 12340 AcAAGCUUCcAGUGGUGUUdTsdT antis
    2513-2532 10341 ACACCACUGGAAGCUUGUG 12341 AcAccAcuGGAAGcuuGuGdTsdT sense
    2513-2532 10342 CACAAGCUUCCAGUGGUGU 12342 cAcAAGCUUCcAGUGGUGUdTsdT antis
    2514-2533 10343 CACCACUGGAAGCUUGUGC 12343 cAccAcuGGAAGcuuGuGcdTsdT sense
    2514-2533 10344 GCACAAGCUUCCAGUGGUG 12344 GcAcAAGCUUCcAGUGGUGdTsdT antis
    2515-2534 10345 ACCACUGGAAGCUUGUGCA 12345 AccAcuGGAAGcuuGuGcAdTsdT sense
    2515-2534 10346 UGCACAAGCUUCCAGUGGU 12346 UGcAcAAGCUUCcAGUGGUdTsdT antis
    2517-2536 10347 CACUGGAAGCUUGUGCACA 12347 cAcuGGAAGcuuGuGcAcAdTsdT sense
    2517-2536 10348 UGUGCACAAGCUUCCAGUG 12348 UGUGcAcAAGCUUCcAGUGdTsdT antis
    2519-2538 10349 CUGGAAGCUUGUGCACAUU 12349 cuGGAAGcuuGuGcAcAuudTsdT sense
    2519-2538 10350 AAUGUGCACAAGCUUCCAG 12350 AAUGUGcAcAAGCUUCcAGdTsdT antis
    2520-2539 10351 UGGAAGCUUGUGCACAUUC 12351 uGGAAGcuuGuGcAcAuucdTsdT sense
    2520-2539 10352 GAAUGUGCACAAGCUUCCA 12352 GAAUGUGcAcAAGCUUCcAdTsdT antis
    2521-2540 10353 GGAAGCUUGUGCACAUUCA 12353 GGAAGcuuGuGcAcAuucAdTsdT sense
    2521-2540 10354 UGAAUGUGCACAAGCUUCC 12354 UGAAUGUGcAcAAGCUUCCdTsdT antis
    2522-2541 10355 GAAGCUUGUGCACAUUCAU 12355 GAAGcuuGuGcAcAuucAudTsdT sense
    2522-2541 10356 AUGAAUGUGCACAAGCUUC 12356 AUGAAUGUGcAcAAGCUUCdTsdT antis
    2524-2543 10357 AGCUUGUGCACAUUCAUUU 12357 AGcuuGuGcAcAuucAuuudTsdT sense
    2524-2543 10358 AAAUGAAUGUGCACAAGCU 12358 AAAUGAAUGUGcAcAAGCUdTsdT antis
    1560-1579 10359 AGAGCUGCAAGCCAGUGCA 12359 AGAGcuGcAAGccAGuGcAdTsdT sense
    1560-1579 10360 UGCACUGGCUUGCAGCUCU 12360 UGcACUGGCUUGcAGCUCUdTsdT antis
    1561-1580 10361 GAGCUGCAAGCCAGUGCAG 12361 GAGcuGcAAGccAGuGcAGdTsdT sense
    1561-1580 10362 CUGCACUGGCUUGCAGCUC 12362 CUGcACUGGCUUGcAGCUCdTsdT antis
    1575-1594 10363 UGCAGCAGCCUUCAGCUUU 12363 uGcAGcAGccuucAGcuuudTsdT sense
    1575-1594 10364 AAAGCUGAAGGCUGCUGCA 12364 AAAGCUGAAGGCUGCUGcAdTsdT antis
    1611-1630 10365 GCAGAGAUAAAGAUGGCAG 12365 GcAGAGAuAAAGAuGGcAGdTsdT sense
    1611-1630 10366 CUGCCAUCUUUAUCUCUGC 12366 CUGCcAUCUUuAUCUCUGCdTsdT antis
    1661-1680 10367 CAGGGUCCUGACAGGCCAC 12367 cAGGGuccuGAcAGGccAcdTsdT sense
    1661-1680 10368 GUGGCCUGUCAGGACCCUG 12368 GUGGCCUGUcAGGACCCUGdTsdT antis
    1779-1798 10369 AGAAAGUUCUACAGGACAA 12369 AGAAAGuucuAcAGGAcAAdTsdT sense
    1779-1798 10370 UUGUCCUGUAGAACUUUCU 12370 UUGUCCUGuAGAACUUUCUdTsdT antis
    1917-1936 10371 UGCUGGACUAUGUUCCGGA 12371 uGcuGGAcuAuGuuccGGAdTsdT sense
    1917-1936 10372 UCCGGAACAUAGUCCAGCA 12372 UCCGGAAcAuAGUCcAGcAdTsdT antis
    2012-2031 10373 UAUCAGCUGUUCAGAAGUC 12373 uAucAGcuGuucAGAAGucdTsdT sense
    2012-2031 10374 GACUUCUGAACAGCUGAUA 12374 GACUUCUGAAcAGCUGAuAdTsdT antis
    2042-2061 10375 CAUUCCUUUGGAAUCUGCC 12375 cAuuccuuuGGAAucuGccdTsdT sense
    2042-2061 10376 GGCAGAUUCCAAAGGAAUG 12376 GGcAGAUUCcAAAGGAAUGdTsdT antis
    2053-2072 10377 AAUCUGCCAUCGAGACAUU 12377 AAucuGccAucGAGAcAuudTsdT sense
    2053-2072 10378 AAUGUCUCGAUGGCAGAUU 12378 AAUGUCUCGAUGGcAGAUUdTsdT antis
    2066-2085 10379 GACAUUAAACCACAGAACC 12379 GAcAuuAAAccAcAGAAccdTsdT sense
    2066-2085 10380 GGUUCUGUGGUUUAAUGUC 12380 GGUUCUGUGGUUuAAUGUCdTsdT antis
    2149-2168 10381 CCGAGGAGAGCCCAAUGUU 12381 ccGAGGAGAGcccAAuGuudTsdT sense
    2149-2168 10382 AACAUUGGGCUCUCCUCGG 12382 AAcAUUGGGCUCUCCUCGGdTsdT antis
    2248-2267 10383 GUCUGCAGGCUGUGUGUUG 12383 GucuGcAGGcuGuGuGuuGdTsdT sense
    2248-2267 10384 CAACACACAGCCUGCAGAC 12384 cAAcAcAcAGCCUGcAGACdTsdT antis
    2302-2321 10385 GGACAGUGGUGUGGAUCAG 12385 GGAcAGuGGuGuGGAucAGdTsdT sense
    2302-2321 10386 CUGAUCCACACCACUGUCC 12386 CUGAUCcAcACcACUGUCCdTsdT antis
    2330-2349 10387 AUAAUAAAGGUCCUAGGAA 12387 AuAAuAAAGGuccuAGGAAdTsdT sense
    2330-2349 10388 UUCCUAGGACCUUUAUUAU 12388 UUCCuAGGACCUUuAUuAUdTsdT antis
    2362-2381 10389 GCAAAUUAGAGAAAUGAAC 12389 GcAAAuuAGAGAAAuGAAcdTsdT sense
    2362-2381 10390 GUUCAUUUCUCUAAUUUGC 12390 GUUcAUUUCUCuAAUUUGCdTsdT antis
    2366-2385 10391 AUUAGAGAAAUGAACCCAA 12391 AuuAGAGAAAuGAAcccAAdTsdT sense
    2366-2385 10392 UUGGGUUCAUUUCUCUAAU 12392 UUGGGUUcAUUUCUCuAAUdTsdT antis
    2378-2397 10393 AACCCAAAUUAUACAGAAU 12393 AAcccAAAuuAuAcAGAAudTsdT sense
    2378-2397 10394 AUUCUGUAUAAUUUGGGUU 12394 AUUCUGuAuAAUUUGGGUUdTsdT antis
    2432-2451 10395 AAGGUCUUCCGGCCCCGAA 12395 AAGGucuuccGGccccGAAdTsdT sense
    2432-2451 10396 UUCGGGGCCGGAAGACCUU 12396 UUCGGGGCCGGAAGACCUUdTsdT antis
    2441-2460 10397 CGGCCCCGAACUCCACCAG 12397 cGGccccGAAcuccAccAGdTsdT sense
    2441-2460 10398 CUGGUGGAGUUCGGGGCCG 12398 CUGGUGGAGUUCGGGGCCGdTsdT antis
    2456-2475 10399 CCAGAGGCAAUUGCACUGU 12399 ccAGAGGcAAuuGcAcuGudTsdT sense
    2456-2475 10400 ACAGUGCAAUUGCCUCUGG 12400 AcAGUGcAAUUGCCUCUGGdTsdT antis
    2472-2491 10401 UGUGCAGCCGUCUGCUGGA 12401 uGuGcAGccGucuGcuGGAdTsdT sense
    2472-2491 10402 UCCAGCAGACGGCUGCACA 12402 UCcAGcAGACGGCUGcAcAdTsdT antis
    1538-1557 10403 CCGAGAACCACCUCCUUUG 12403 ccGAGAAccAccuccuuuGdTsdT sense
    1538-1557 10404 CAAAGGAGGUGGUUCUCGG 12404 cAAAGGAGGUGGUUCUCGGdTsdT antis
    1539-1558 10405 CGAGAACCACCUCCUUUGC 12405 cGAGAAccAccuccuuuGcdTsdT sense
    1539-1558 10406 GCAAAGGAGGUGGUUCUCG 12406 GcAAAGGAGGUGGUUCUCGdTsdT antis
    1547-1566 10407 ACCUCCUUUGCGGAGAGCU 12407 AccuccuuuGcGGAGAGcudTsdT sense
    1547-1566 10408 AGCUCUCCGCAAAGGAGGU 12408 AGCUCUCCGcAAAGGAGGUdTsdT antis
    1551-1570 10409 CCUUUGCGGAGAGCUGCAA 12409 ccuuuGcGGAGAGcuGcAAdTsdT sense
    1551-1570 10410 UUGCAGCUCUCCGCAAAGG 12410 UUGcAGCUCUCCGcAAAGGdTsdT antis
    1558-1577 10411 GGAGAGCUGCAAGCCAGUG 12411 GGAGAGcuGcAAGccAGuGdTsdT sense
    1558-1577 10412 CACUGGCUUGCAGCUCUCC 12412 cACUGGCUUGcAGCUCUCCdTsdT antis
    1573-1592 10413 AGUGCAGCAGCCUUCAGCU 12413 AGuGcAGcAGccuucAGcudTsdT sense
    1573-1592 10414 AGCUGAAGGCUGCUGCACU 12414 AGCUGAAGGCUGCUGcACUdTsdT antis
    1574-1593 10415 GUGCAGCAGCCUUCAGCUU 12415 GuGcAGcAGccuucAGcuudTsdT sense
    1574-1593 10416 AAGCUGAAGGCUGCUGCAC 12416 AAGCUGAAGGCUGCUGcACdTsdT antis
    1584-1603 10417 CUUCAGCUUUUGGUAGCAU 12417 cuucAGcuuuuGGuAGcAudTsdT sense
    1584-1603 10418 AUGCUACCAAAAGCUGAAG 12418 AUGCuACcAAAAGCUGAAGdTsdT antis
    1594-1613 10419 UGGUAGCAUGAAAGUUAGC 12419 uGGuAGcAuGAAAGuuAGcdTsdT sense
    1594-1613 10420 GCUAACUUUCAUGCUACCA 12420 GCuAACUUUcAUGCuACcAdTsdT antis
    1599-1618 10421 GCAUGAAAGUUAGCAGAGA 12421 GcAuGAAAGuuAGcAGAGAdTsdT sense
    1599-1618 10422 UCUCUGCUAACUUUCAUGC 12422 UCUCUGCuAACUUUcAUGCdTsdT antis
    1600-1619 10423 CAUGAAAGUUAGCAGAGAU 12423 cAuGAAAGuuAGcAGAGAudTsdT sense
    1600-1619 10424 AUCUCUGCUAACUUUCAUG 12424 AUCUCUGCuAACUUUcAUGdTsdT antis
    1613-1632 10425 AGAGAUAAAGAUGGCAGCA 12425 AGAGAuAAAGAuGGcAGcAdTsdT sense
    1613-1632 10426 UGCUGCCAUCUUUAUCUCU 12426 UGCUGCcAUCUUuAUCUCUdTsdT antis
    1614-1633 10427 GAGAUAAAGAUGGCAGCAA 12427 GAGAuAAAGAuGGcAGcAAdTsdT sense
    1614-1633 10428 UUGCUGCCAUCUUUAUCUC 12428 UUGCUGCcAUCUUuAUCUCdTsdT antis
    1630-1649 10429 CAAGGUAACCACAGUAGUG 12429 cAAGGuAAccAcAGuAGuGdTsdT sense
    1630-1649 10430 CACUACUGUGGUUACCUUG 12430 cACuACUGUGGUuACCUUGdTsdT antis
    1650-1669 10431 CAACUCCUGGCCAGGGUCC 12431 cAAcuccuGGccAGGGuccdTsdT sense
    1650-1669 10432 GGACCCUGGCCAGGAGUUG 12432 GGACCCUGGCcAGGAGUUGdTsdT antis
    1652-1671 10433 ACUCCUGGCCAGGGUCCUG 12433 AcuccuGGccAGGGuccuGdTsdT sense
    1652-1671 10434 CAGGACCCUGGCCAGGAGU 12434 cAGGACCCUGGCcAGGAGUdTsdT antis
    1653-1672 10435 CUCCUGGCCAGGGUCCUGA 12435 cuccuGGccAGGGuccuGAdTsdT sense
    1653-1672 10436 UCAGGACCCUGGCCAGGAG 12436 UcAGGACCCUGGCcAGGAGdTsdT antis
    1654-1673 10437 UCCUGGCCAGGGUCCUGAC 12437 uccuGGccAGGGuccuGAcdTsdT sense
    1654-1673 10438 GUCAGGACCCUGGCCAGGA 12438 GUcAGGACCCUGGCcAGGAdTsdT antis
    1665-1684 10439 GUCCUGACAGGCCACAGGA 12439 GuccuGAcAGGccAcAGGAdTsdT sense
    1665-1684 10440 UCCUGUGGCCUGUCAGGAC 12440 UCCUGUGGCCUGUcAGGACdTsdT antis
    1673-1692 10441 AGGCCACAGGAAGUCAGUU 12441 AGGccAcAGGAAGucAGuudTsdT sense
    1673-1692 10442 AACUGACUUCCUGUGGCCU 12442 AACUGACUUCCUGUGGCCUdTsdT antis
    1688-1707 10443 AGUUAUACAGACACGAAAG 12443 AGuuAuAcAGAcAcGAAAGdTsdT sense
    1688-1707 10444 CUUUCGUGUCUGUAUAACU 12444 CUUUCGUGUCUGuAuAACUdTsdT antis
    1743-1762 10445 CCAAACUUUGUGAUUCUGG 12445 ccAAAcuuuGuGAuucuGGdTsdT sense
    1743-1762 10446 CCAGAAUCACAAAGUUUGG 12446 CcAGAAUcAcAAAGUUUGGdTsdT antis
    1744-1763 10447 CAAACUUUGUGAUUCUGGA 12447 cAAAcuuuGuGAuucuGGAdTsdT sense
    1744-1763 10448 UCCAGAAUCACAAAGUUUG 12448 UCcAGAAUcAcAAAGUUUGdTsdT antis
    1745-1764 10449 AAACUUUGUGAUUCUGGAG 12449 AAAcuuuGuGAuucuGGAGdTsdT sense
    1745-1764 10450 CUCCAGAAUCACAAAGUUU 12450 CUCcAGAAUcAcAAAGUUUdTsdT antis
    1746-1765 10451 AACUUUGUGAUUCUGGAGA 12451 AAcuuuGuGAuucuGGAGAdTsdT sense
    1746-1765 10452 UCUCCAGAAUCACAAAGUU 12452 UCUCcAGAAUcAcAAAGUUdTsdT antis
    1780-1799 10453 GAAAGUUCUACAGGACAAG 12453 GAAAGuucuAcAGGAcAAGdTsdT sense
    1780-1799 10454 CUUGUCCUGUAGAACUUUC 12454 CUUGUCCUGuAGAACUUUCdTsdT antis
    1781-1800 10455 AAAGUUCUACAGGACAAGC 12455 AAAGuucuAcAGGAcAAGcdTsdT sense
    1781-1800 10456 GCUUGUCCUGUAGAACUUU 12456 GCUUGUCCUGuAGAACUUUdTsdT antis
    1782-1801 10457 AAGUUCUACAGGACAAGCG 12457 AAGuucuAcAGGAcAAGcGdTsdT sense
    1782-1801 10458 CGCUUGUCCUGUAGAACUU 12458 CGCUUGUCCUGuAGAACUUdTsdT antis
    1809-1828 10459 ACCGAGAGCUCCAGAUCAU 12459 AccGAGAGcuccAGAucAudTsdT sense
    1809-1828 10460 AUGAUCUGGAGCUCUCGGU 12460 AUGAUCUGGAGCUCUCGGUdTsdT antis
    1880-1899 10461 AGUGGUGAGAAGAAAGAUG 12461 AGuGGuGAGAAGAAAGAuGdTsdT sense
    1880-1899 10462 CAUCUUUCUUCUCACCACU 12462 cAUCUUUCUUCUcACcACUdTsdT antis
    1885-1904 10463 UGAGAAGAAAGAUGAGGUC 12463 uGAGAAGAAAGAuGAGGucdTsdT sense
    1885-1904 10464 GACCUCAUCUUUCUUCUCA 12464 GACCUcAUCUUUCUUCUcAdTsdT antis
    1889-1908 10465 AAGAAAGAUGAGGUCUACC 12465 AAGAAAGAuGAGGucuAccdTsdT sense
    1889-1908 10466 GGUAGACCUCAUCUUUCUU 12466 GGuAGACCUcAUCUUUCUUdTsdT antis
    2043-2062 10467 AUUCCUUUGGAAUCUGCCA 12467 AuuccuuuGGAAucuGccAdTsdT sense
    2043-2062 10468 UGGCAGAUUCCAAAGGAAU 12468 UGGcAGAUUCcAAAGGAAUdTsdT antis
    2050-2069 10469 UGGAAUCUGCCAUCGAGAC 12469 uGGAAucuGccAucGAGAcdTsdT sense
    2050-2069 10470 GUCUCGAUGGCAGAUUCCA 12470 GUCUCGAUGGcAGAUUCcAdTsdT antis
    2092-2111 10471 GGAUCCUGAUACAGCUGUA 12471 GGAuccuGAuAcAGcuGuAdTsdT sense
    2092-2111 10472 UACAGCUGUAUCAGGAUCC 12472 uAcAGCUGuAUcAGGAUCCdTsdT antis
    2116-2135 10473 ACUCUGUGACUUUGGAAGU 12473 AcucuGuGAcuuuGGAAGudTsdT sense
    2116-2135 10474 ACUUCCAAAGUCACAGAGU 12474 ACUUCcAAAGUcAcAGAGUdTsdT antis
    2143-2162 10475 GCUGGUCCGAGGAGAGCCC 12475 GcuGGuccGAGGAGAGcccdTsdT sense
    2143-2162 10476 GGGCUCUCCUCGGACCAGC 12476 GGGCUCUCCUCGGACcAGCdTsdT antis
    2159-2178 10477 CCCAAUGUUUCAUAUAUCU 12477 cccAAuGuuucAuAuAucudTsdT sense
    2159-2178 10478 AGAUAUAUGAAACAUUGGG 12478 AGAuAuAUGAAAcAUUGGGdTsdT antis
    2163-2182 10479 AUGUUUCAUAUAUCUGUUC 12479 AuGuuucAuAuAucuGuucdTsdT sense
    2163-2182 10480 GAACAGAUAUAUGAAACAU 12480 GAAcAGAuAuAUGAAAcAUdTsdT antis
    2207-2226 10481 AUCUUUGGAGCCACUGAUU 12481 AucuuuGGAGccAcuGAuudTsdT sense
    2207-2226 10482 AAUCAGUGGCUCCAAAGAU 12482 AAUcAGUGGCUCcAAAGAUdTsdT antis
    2247-2266 10483 GGUCUGCAGGCUGUGUGUU 12483 GGucuGcAGGcuGuGuGuudTsdT sense
    2247-2266 10484 AACACACAGCCUGCAGACC 12484 AAcAcAcAGCCUGcAGACCdTsdT antis
    2251-2270 10485 UGCAGGCUGUGUGUUGGCU 12485 uGcAGGcuGuGuGuuGGcudTsdT sense
    2251-2270 10486 AGCCAACACACAGCCUGCA 12486 AGCcAAcAcAcAGCCUGcAdTsdT antis
    2261-2280 10487 GUGUUGGCUGAAUUGUUGC 12487 GuGuuGGcuGAAuuGuuGcdTsdT sense
    2261-2280 10488 GCAACAAUUCAGCCAACAC 12488 GcAAcAAUUcAGCcAAcACdTsdT antis
    2298-2317 10489 CUGGGGACAGUGGUGUGGA 12489 cuGGGGAcAGuGGuGuGGAdTsdT sense
    2298-2317 10490 UCCACACCACUGUCCCCAG 12490 UCcAcACcACUGUCCCcAGdTsdT antis
    2300-2319 10491 GGGGACAGUGGUGUGGAUC 12491 GGGGAcAGuGGuGuGGAucdTsdT sense
    2300-2319 10492 GAUCCACACCACUGUCCCC 12492 GAUCcAcACcACUGUCCCCdTsdT antis
    2301-2320 10493 GGGACAGUGGUGUGGAUCA 12493 GGGAcAGuGGuGuGGAucAdTsdT sense
    2301-2320 10494 UGAUCCACACCACUGUCCC 12494 UGAUCcAcACcACUGUCCCdTsdT antis
    2319-2338 10495 AGUUGGUGGAAAUAAUAAA 12495 AGuuGGuGGAAAuAAuAAAdTsdT sense
    2319-2338 10496 UUUAUUAUUUCCACCAACU 12496 UUuAUuAUUUCcACcAACUdTsdT antis
    2323-2342 10497 GGUGGAAAUAAUAAAGGUC 12497 GGuGGAAAuAAuAAAGGucdTsdT sense
    2323-2342 10498 GACCUUUAUUAUUUCCACC 12498 GACCUUuAUuAUUUCcACCdTsdT antis
    2325-2344 10499 UGGAAAUAAUAAAGGUCCU 12499 uGGAAAuAAuAAAGGuccudTsdT sense
    2325-2344 10500 AGGACCUUUAUUAUUUCCA 12500 AGGACCUUuAUuAUUUCcAdTsdT antis
    2363-2382 10501 CAAAUUAGAGAAAUGAACC 12501 cAAAuuAGAGAAAuGAAccdTsdT sense
    2363-2382 10502 GGUUCAUUUCUCUAAUUUG 12502 GGUUcAUUUCUCuAAUUUGdTsdT antis
    2376-2395 10503 UGAACCCAAAUUAUACAGA 12503 uGAAcccAAAuuAuAcAGAdTsdT sense
    2376-2395 10504 UCUGUAUAAUUUGGGUUCA 12504 UCUGuAuAAUUUGGGUUcAdTsdT antis
    2377-2396 10505 GAACCCAAAUUAUACAGAA 12505 GAAcccAAAuuAuAcAGAAdTsdT sense
    2377-2396 10506 UUCUGUAUAAUUUGGGUUC 12506 UUCUGuAuAAUUUGGGUUCdTsdT antis
    2383-2402 10507 AAAUUAUACAGAAUUCAAA 12507 AAAuuAuAcAGAAuucAAAdTsdT sense
    2383-2402 10508 UUUGAAUUCUGUAUAAUUU 12508 UUUGAAUUCUGuAuAAUUUdTsdT antis
    2391-2410 10509 CAGAAUUCAAAUUCCCUCA 12509 cAGAAuucAAAuucccucAdTsdT sense
    2391-2410 10510 UGAGGGAAUUUGAAUUCUG 12510 UGAGGGAAUUUGAAUUCUGdTsdT antis
    2394-2413 10511 AAUUCAAAUUCCCUCAAAU 12511 AAuucAAAuucccucAAAudTsdT sense
    2394-2413 10512 AUUUGAGGGAAUUUGAAUU 12512 AUUUGAGGGAAUUUGAAUUdTsdT antis
    2436-2455 10513 UCUUCCGGCCCCGAACUCC 12513 ucuuccGGccccGAAcuccdTsdT sense
    2436-2455 10514 GGAGUUCGGGGCCGGAAGA 12514 GGAGUUCGGGGCCGGAAGAdTsdT antis
    2442-2461 10515 GGCCCCGAACUCCACCAGA 12515 GGccccGAAcuccAccAGAdTsdT sense
    2442-2461 10516 UCUGGUGGAGUUCGGGGCC 12516 UCUGGUGGAGUUCGGGGCCdTsdT antis
    2449-2468 10517 AACUCCACCAGAGGCAAUU 12517 AAcuccAccAGAGGcAAuudTsdT sense
    2449-2468 10518 AAUUGCCUCUGGUGGAGUU 12518 AAUUGCCUCUGGUGGAGUUdTsdT antis
    2450-2469 10519 ACUCCACCAGAGGCAAUUG 12519 AcuccAccAGAGGcAAuuGdTsdT sense
    2450-2469 10520 CAAUUGCCUCUGGUGGAGU 12520 cAAUUGCCUCUGGUGGAGUdTsdT antis
    2457-2476 10521 CAGAGGCAAUUGCACUGUG 12521 cAGAGGcAAuuGcAcuGuGdTsdT sense
    2457-2476 10522 CACAGUGCAAUUGCCUCUG 12522 cAcAGUGcAAUUGCCUCUGdTsdT antis
    2470-2489 10523 ACUGUGCAGCCGUCUGCUG 12523 AcuGuGcAGccGucuGcuGdTsdT sense
    2470-2489 10524 CAGCAGACGGCUGCACAGU 12524 cAGcAGACGGCUGcAcAGUdTsdT antis
    2473-2492 10525 GUGCAGCCGUCUGCUGGAG 12525 GuGcAGccGucuGcuGGAGdTsdT sense
    2473-2492 10526 CUCCAGCAGACGGCUGCAC 12526 CUCcAGcAGACGGCUGcACdTsdT antis
    2475-2494 10527 GCAGCCGUCUGCUGGAGUA 12527 GcAGccGucuGcuGGAGuAdTsdT sense
    2475-2494 10528 UACUCCAGCAGACGGCUGC 12528 uACUCcAGcAGACGGCUGCdTsdT antis
    1612-1631 10529 CAGAGAUAAAGAUGGCAGC 12529 cAGAGAuAAAGAuGGcAGcdTsdT sense
    1612-1631 10530 GCUGCCAUCUUUAUCUCUG 12530 GCUGCcAUCUUuAUCUCUGdTsdT antis
    1804-1823 10531 UAAGAACCGAGAGCUCCAG 12531 uAAGAAccGAGAGcuccAGdTsdT sense
    1804-1823 10532 CUGGAGCUCUCGGUUCUUA 12532 CUGGAGCUCUCGGUUCUuAdTsdT antis
    1805-1824 10533 AAGAACCGAGAGCUCCAGA 12533 AAGAAccGAGAGcuccAGAdTsdT sense
    1805-1824 10534 UCUGGAGCUCUCGGUUCUU 12534 UCUGGAGCUCUCGGUUCUUdTsdT antis
    1888-1907 10535 GAAGAAAGAUGAGGUCUAC 12535 GAAGAAAGAuGAGGucuAcdTsdT sense
    1888-1907 10536 GUAGACCUCAUCUUUCUUC 12536 GuAGACCUcAUCUUUCUUCdTsdT antis
    2165-2184 10537 GUUUCAUAUAUCUGUUCUC 12537 GuuucAuAuAucuGuucucdTsdT sense
    2165-2184 10538 GAGAACAGAUAUAUGAAAC 12538 GAGAAcAGAuAuAUGAAACdTsdT antis
    2332-2351 10539 AAUAAAGGUCCUAGGAACA 12539 AAuAAAGGuccuAGGAAcAdTsdT sense
    2332-2351 10540 UGUUCCUAGGACCUUUAUU 12540 UGUUCCuAGGACCUUuAUUdTsdT antis
    2518-2537 10541 ACUGGAAGCUUGUGCACAU 12541 AcuGGAAGcuuGuGcAcAudTsdT sense
    2518-2537 10542 AUGUGCACAAGCUUCCAGU 12542 AUGUGcAcAAGCUUCcAGUdTsdT antis
    1565-1584 10543 UGCAAGCCAGUGCAGCAGC 12543 uGcAAGccAGuGcAGcAGcdTsdT sense
    1565-1584 10544 GCUGCUGCACUGGCUUGCA 12544 GCUGCUGcACUGGCUUGcAdTsdT antis
    1569-1588 10545 AGCCAGUGCAGCAGCCUUC 12545 AGccAGuGcAGcAGccuucdTsdT sense
    1569-1588 10546 GAAGGCUGCUGCACUGGCU 12546 GAAGGCUGCUGcACUGGCUdTsdT antis
    1631-1650 10547 AAGGUAACCACAGUAGUGG 12547 AAGGuAAccAcAGuAGuGGdTsdT sense
    1631-1650 10548 CCACUACUGUGGUUACCUU 12548 CcACuACUGUGGUuACCUUdTsdT antis
    1659-1678 10549 GCCAGGGUCCUGACAGGCC 12549 GccAGGGuccuGAcAGGccdTsdT sense
    1659-1678 10550 GGCCUGUCAGGACCCUGGC 12550 GGCCUGUcAGGACCCUGGCdTsdT antis
    1711-1730 10551 UGGAAAUGGAUCAUUUGGU 12551 uGGAAAuGGAucAuuuGGudTsdT sense
    1711-1730 10552 ACCAAAUGAUCCAUUUCCA 12552 ACcAAAUGAUCcAUUUCcAdTsdT antis
    1756-1775 10553 UUCUGGAGAACUGGUUGCC 12553 uucuGGAGAAcuGGuuGccdTsdT sense
    1756-1775 10554 GGCAACCAGUUCUCCAGAA 12554 GGcAACcAGUUCUCcAGAAdTsdT antis
    1761-1780 10555 GAGAACUGGUUGCCAUCAA 12555 GAGAAcuGGuuGccAucAAdTsdT sense
    1761-1780 10556 UUGAUGGCAACCAGUUCUC 12556 UUGAUGGcAACcAGUUCUCdTsdT antis
    1762-1781 10557 AGAACUGGUUGCCAUCAAG 12557 AGAAcuGGuuGccAucAAGdTsdT sense
    1762-1781 10558 CUUGAUGGCAACCAGUUCU 12558 CUUGAUGGcAACcAGUUCUdTsdT antis
    1997-2016 10559 GUCAAGUUGUAUAUGUAUC 12559 GucAAGuuGuAuAuGuAucdTsdT sense
    1997-2016 10560 GAUACAUAUACAACUUGAC 12560 GAuAcAuAuAcAACUUGACdTsdT antis
    2040-2059 10561 UCCAUUCCUUUGGAAUCUG 12561 uccAuuccuuuGGAAucuGdTsdT sense
    2040-2059 10562 CAGAUUCCAAAGGAAUGGA 12562 cAGAUUCcAAAGGAAUGGAdTsdT antis
    2133-2152 10563 GUGCAAAGCAGCUGGUCCG 12563 GuGcAAAGcAGcuGGuccGdTsdT sense
    2133-2152 10564 CGGACCAGCUGCUUUGCAC 12564 CGGACcAGCUGCUUUGcACdTsdT antis
    2186-2205 10565 UACUACAGGGCACCAGAGU 12565 uAcuAcAGGGcAccAGAGudTsdT sense
    2186-2205 10566 ACUCUGGUGCCCUGUAGUA 12566 ACUCUGGUGCCCUGuAGuAdTsdT antis
    2250-2269 10567 CUGCAGGCUGUGUGUUGGC 12567 cuGcAGGcuGuGuGuuGGcdTsdT sense
    2250-2269 10568 GCCAACACACAGCCUGCAG 12568 GCcAAcAcAcAGCCUGcAGdTsdT antis
    2466-2485 10569 UUGCACUGUGCAGCCGUCU 12569 uuGcAcuGuGcAGccGucudTsdT sense
    2466-2485 10570 AGACGGCUGCACAGUGCAA 12570 AGACGGCUGcAcAGUGcAAdTsdT antis
    2523-2542 10571 AAGCUUGUGCACAUUCAUU 12571 AAGcuuGuGcAcAuucAuudTsdT sense
    2523-2542 10572 AAUGAAUGUGCACAAGCUU 12572 AAUGAAUGUGcAcAAGCUUdTsdT antis
    1548-1567 10573 CCUCCUUUGCGGAGAGCUG 12573 ccuccuuuGcGGAGAGcuGdTsdT sense
    1548-1567 10574 CAGCUCUCCGCAAAGGAGG 12574 cAGCUCUCCGcAAAGGAGGdTsdT antis
    1566-1585 10575 GCAAGCCAGUGCAGCAGCC 12575 GcAAGccAGuGcAGcAGccdTsdT sense
    1566-1585 10576 GGCUGCUGCACUGGCUUGC 12576 GGCUGCUGcACUGGCUUGCdTsdT antis
    1656-1675 10577 CUGGCCAGGGUCCUGACAG 12577 cuGGccAGGGuccuGAcAGdTsdT sense
    1656-1675 10578 CUGUCAGGACCCUGGCCAG 12578 CUGUcAGGACCCUGGCcAGdTsdT antis
    1763-1782 10579 GAACUGGUUGCCAUCAAGA 12579 GAAcuGGuuGccAucAAGAdTsdT sense
    1763-1782 10580 UCUUGAUGGCAACCAGUUC 12580 UCUUGAUGGcAACcAGUUCdTsdT antis
    2185-2204 10581 GUACUACAGGGCACCAGAG 12581 GuAcuAcAGGGcAccAGAGdTsdT sense
    2185-2204 10582 CUCUGGUGCCCUGUAGUAC 12582 CUCUGGUGCCCUGuAGuACdTsdT antis
    2212-2231 10583 UGGAGCCACUGAUUACACG 12583 uGGAGccAcuGAuuAcAcGdTsdT sense
    2212-2231 10584 CGUGUAAUCAGUGGCUCCA 12584 CGUGuAAUcAGUGGCUCcAdTsdT antis
    2265-2284 10585 UGGCUGAAUUGUUGCUAGG 12585 uGGcuGAAuuGuuGcuAGGdTsdT sense
    2265-2284 10586 CCUAGCAACAAUUCAGCCA 12586 CCuAGcAAcAAUUcAGCcAdTsdT antis
    2326-2345 10587 GGAAAUAAUAAAGGUCCUA 12587 GGAAAuAAuAAAGGuccuAdTsdT sense
    2326-2345 10588 UAGGACCUUUAUUAUUUCC 12588 uAGGACCUUuAUuAUUUCCdTsdT antis
    2425-2444 10589 UUGGACAAAGGUCUUCCGG 12589 uuGGAcAAAGGucuuccGGdTsdT sense
    2425-2444 10590 CCGGAAGACCUUUGUCCAA 12590 CCGGAAGACCUUUGUCcAAdTsdT antis
    1962-1981 10591 AUAGUCGAGCCAAGCAGAC 12591 AuAGucGAGccAAGcAGAcdTsdT sense
    1962-1981 10592 GUCUGCUUGGCUCGACUAU 12592 GUCUGCUUGGCUCGACuAUdTsdT antis
    1803-1822 10593 UUAAGAACCGAGAGCUCCA 12593 uuAAGAAccGAGAGcuccAdTsdT sense
    1803-1822 10594 UGGAGCUCUCGGUUCUUAA 12594 UGGAGCUCUCGGUUCUuAAdTsdT antis
    1808-1827 10595 AACCGAGAGCUCCAGAUCA 12595 AAccGAGAGcuccAGAucAdTsdT sense
    1808-1827 10596 UGAUCUGGAGCUCUCGGUU 12596 UGAUCUGGAGCUCUCGGUUdTsdT antis
    1603-1622 10597 GAAAGUUAGCAGAGAUAAA 12597 GAAAGuuAGcAGAGAuAAAdTsdT sense
    1603-1622 10598 UUUAUCUCUGCUAACUUUC 12598 UUuAUCUCUGCuAACUUUCdTsdT antis
    1640-1659 10599 ACAGUAGUGGCAACUCCUG 12599 AcAGuAGuGGcAAcuccuGdTsdT sense
    1640-1659 10600 CAGGAGUUGCCACUACUGU 12600 cAGGAGUUGCcACuACUGUdTsdT antis
    1718-1737 10601 GGAUCAUUUGGUGUGGUAU 12601 GGAucAuuuGGuGuGGuAudTsdT sense
    1718-1737 10602 AUACCACACCAAAUGAUCC 12602 AuACcAcACcAAAUGAUCCdTsdT antis
    1807-1826 10603 GAACCGAGAGCUCCAGAUC 12603 GAAccGAGAGcuccAGAucdTsdT sense
    1807-1826 10604 GAUCUGGAGCUCUCGGUUC 12604 GAUCUGGAGCUCUCGGUUCdTsdT antis
    1904-1923 10605 UACCUUAACCUGGUGCUGG 12605 uAccuuAAccuGGuGcuGGdTsdT sense
    1904-1923 10606 CCAGCACCAGGUUAAGGUA 12606 CcAGcACcAGGUuAAGGuAdTsdT antis
    1905-1924 10607 ACCUUAACCUGGUGCUGGA 12607 AccuuAAccuGGuGcuGGAdTsdT sense
    1905-1924 10608 UCCAGCACCAGGUUAAGGU 12608 UCcAGcACcAGGUuAAGGUdTsdT antis
    1906-1925 10609 CCUUAACCUGGUGCUGGAC 12609 ccuuAAccuGGuGcuGGAcdTsdT sense
    1906-1925 10610 GUCCAGCACCAGGUUAAGG 12610 GUCcAGcACcAGGUuAAGGdTsdT antis
    2015-2034 10611 CAGCUGUUCAGAAGUCUAG 12611 cAGcuGuucAGAAGucuAGdTsdT sense
    2015-2034 10612 CUAGACUUCUGAACAGCUG 12612 CuAGACUUCUGAAcAGCUGdTsdT antis
    2057-2076 10613 UGCCAUCGAGACAUUAAAC 12613 uGccAucGAGAcAuuAAAcdTsdT sense
    2057-2076 10614 GUUUAAUGUCUCGAUGGCA 12614 GUUuAAUGUCUCGAUGGcAdTsdT antis
    2109-2128 10615 UAUUAAAACUCUGUGACUU 12615 uAuuAAAAcucuGuGAcuudTsdT sense
    2109-2128 10616 AAGUCACAGAGUUUUAAUA 12616 AAGUcAcAGAGUUUuAAuAdTsdT antis
    2126-2145 10617 UUUGGAAGUGCAAAGCAGC 12617 uuuGGAAGuGcAAAGcAGcdTsdT sense
    2126-2145 10618 GCUGCUUUGCACUUCCAAA 12618 GCUGCUUUGcACUUCcAAAdTsdT antis
    2129-2148 10619 GGAAGUGCAAAGCAGCUGG 12619 GGAAGuGcAAAGcAGcuGGdTsdT sense
    2129-2148 10620 CCAGCUGCUUUGCACUUCC 12620 CcAGCUGCUUUGcACUUCCdTsdT antis
    2312-2331 10621 GUGGAUCAGUUGGUGGAAA 12621 GuGGAucAGuuGGuGGAAAdTsdT sense
    2312-2331 10622 UUUCCACCAACUGAUCCAC 12622 UUUCcACcAACUGAUCcACdTsdT antis
    2313-2332 10623 UGGAUCAGUUGGUGGAAAU 12623 uGGAucAGuuGGuGGAAAudTsdT sense
    2313-2332 10624 AUUUCCACCAACUGAUCCA 12624 AUUUCcACcAACUGAUCcAdTsdT antis
    2347-2366 10625 AACACCAACAAGGGAGCAA 12625 AAcAccAAcAAGGGAGcAAdTsdT sense
    2347-2366 10626 UUGCUCCCUUGUUGGUGUU 12626 UUGCUCCCUUGUUGGUGUUdTsdT antis
    2373-2392 10627 AAAUGAACCCAAAUUAUAC 12627 AAAuGAAcccAAAuuAuAcdTsdT sense
    2373-2392 10628 GUAUAAUUUGGGUUCAUUU 12628 GuAuAAUUUGGGUUcAUUUdTsdT antis
    2431-2450 10629 AAAGGUCUUCCGGCCCCGA 12629 AAAGGucuuccGGccccGAdTsdT sense
    2431-2450 10630 UCGGGGCCGGAAGACCUUU 12630 UCGGGGCCGGAAGACCUUUdTsdT antis
    1632-1651 10631 AGGUAACCACAGUAGUGGC 12631 AGGuAAccAcAGuAGuGGcdTsdT sense
    1632-1651 10632 GCCACUACUGUGGUUACCU 12632 GCcACuACUGUGGUuACCUdTsdT antis
    2031-2050 10633 UAGCCUAUAUCCAUUCCUU 12633 uAGccuAuAuccAuuccuudTsdT sense
    2031-2050 10634 AAGGAAUGGAUAUAGGCUA 12634 AAGGAAUGGAuAuAGGCuAdTsdT antis
    1604-1623 10635 AAAGUUAGCAGAGAUAAAG 12635 AAAGuuAGcAGAGAuAAAGdTsdT sense
    1604-1623 10636 CUUUAUCUCUGCUAACUUU 12636 CUUuAUCUCUGCuAACUUUdTsdT antis
    1605-1624 10637 AAGUUAGCAGAGAUAAAGA 12637 AAGuuAGcAGAGAuAAAGAdTsdT sense
    1605-1624 10638 UCUUUAUCUCUGCUAACUU 12638 UCUUuAUCUCUGCuAACUUdTsdT antis
    1634-1653 10639 GUAACCACAGUAGUGGCAA 12639 GuAAccAcAGuAGuGGcAAdTsdT sense
    1634-1653 10640 UUGCCACUACUGUGGUUAC 12640 UUGCcACuACUGUGGUuACdTsdT antis
    1662-1681 10641 AGGGUCCUGACAGGCCACA 12641 AGGGuccuGAcAGGccAcAdTsdT sense
    1662-1681 10642 UGUGGCCUGUCAGGACCCU 12642 UGUGGCCUGUcAGGACCCUdTsdT antis
    1663-1682 10643 GGGUCCUGACAGGCCACAG 12643 GGGuccuGAcAGGccAcAGdTsdT sense
    1663-1682 10644 CUGUGGCCUGUCAGGACCC 12644 CUGUGGCCUGUcAGGACCCdTsdT antis
    1702-1721 10645 GAAAGUGAUUGGAAAUGGA 12645 GAAAGuGAuuGGAAAuGGAdTsdT sense
    1702-1721 10646 UCCAUUUCCAAUCACUUUC 12646 UCcAUUUCcAAUcACUUUCdTsdT antis
    1772-1791 10647 GCCAUCAAGAAAGUUCUAC 12647 GccAucAAGAAAGuucuAcdTsdT sense
    1772-1791 10648 GUAGAACUUUCUUGAUGGC 12648 GuAGAACUUUCUUGAUGGCdTsdT antis
    1776-1795 10649 UCAAGAAAGUUCUACAGGA 12649 ucAAGAAAGuucuAcAGGAdTsdT sense
    1776-1795 10650 UCCUGUAGAACUUUCUUGA 12650 UCCUGuAGAACUUUCUUGAdTsdT antis
    1792-1811 10651 GGACAAGCGAUUUAAGAAC 12651 GGAcAAGcGAuuuAAGAAcdTsdT sense
    1792-1811 10652 GUUCUUAAAUCGCUUGUCC 12652 GUUCUuAAAUCGCUUGUCCdTsdT antis
    1801-1820 10653 AUUUAAGAACCGAGAGCUC 12653 AuuuAAGAAccGAGAGcucdTsdT sense
    1801-1820 10654 GAGCUCUCGGUUCUUAAAU 12654 GAGCUCUCGGUUCUuAAAUdTsdT antis
    1813-1832 10655 AGAGCUCCAGAUCAUGAGA 12655 AGAGcuccAGAucAuGAGAdTsdT sense
    1813-1832 10656 UCUCAUGAUCUGGAGCUCU 12656 UCUcAUGAUCUGGAGCUCUdTsdT antis
    1859-1878 10657 CUGCGGUAUUUCUUCUACU 12657 cuGcGGuAuuucuucuAcudTsdT sense
    1859-1878 10658 AGUAGAAGAAAUACCGCAG 12658 AGuAGAAGAAAuACCGcAGdTsdT antis
    1860-1879 10659 UGCGGUAUUUCUUCUACUC 12659 uGcGGuAuuucuucuAcucdTsdT sense
    1860-1879 10660 GAGUAGAAGAAAUACCGCA 12660 GAGuAGAAGAAAuACCGcAdTsdT antis
    1900-1919 10661 GGUCUACCUUAACCUGGUG 12661 GGucuAccuuAAccuGGuGdTsdT sense
    1900-1919 10662 CACCAGGUUAAGGUAGACC 12662 cACcAGGUuAAGGuAGACCdTsdT antis
    1909-1928 10663 UAACCUGGUGCUGGACUAU 12663 uAAccuGGuGcuGGAcuAudTsdT sense
    1909-1928 10664 AUAGUCCAGCACCAGGUUA 12664 AuAGUCcAGcACcAGGUuAdTsdT antis
    1982-2001 10665 CUCCCUGUGAUCUAUGUCA 12665 cucccuGuGAucuAuGucAdTsdT sense
    1982-2001 10666 UGACAUAGAUCACAGGGAG 12666 UGAcAuAGAUcAcAGGGAGdTsdT antis
    2125-2144 10667 CUUUGGAAGUGCAAAGCAG 12667 cuuuGGAAGuGcAAAGcAGdTsdT sense
    2125-2144 10668 CUGCUUUGCACUUCCAAAG 12668 CUGCUUUGcACUUCcAAAGdTsdT antis
    2137-2156 10669 AAAGCAGCUGGUCCGAGGA 12669 AAAGcAGcuGGuccGAGGAdTsdT sense
    2137-2156 10670 UCCUCGGACCAGCUGCUUU 12670 UCCUCGGACcAGCUGCUUUdTsdT antis
    2156-2175 10671 GAGCCCAAUGUUUCAUAUA 12671 GAGcccAAuGuuucAuAuAdTsdT sense
    2156-2175 10672 UAUAUGAAACAUUGGGCUC 12672 uAuAUGAAAcAUUGGGCUCdTsdT antis
    2174-2193 10673 AUCUGUUCUCGGUACUACA 12673 AucuGuucucGGuAcuAcAdTsdT sense
    2174-2193 10674 UGUAGUACCGAGAACAGAU 12674 UGuAGuACCGAGAAcAGAUdTsdT antis
    2281-2300 10675 AGGACAACCAAUAUUUCCU 12675 AGGAcAAccAAuAuuuccudTsdT sense
    2281-2300 10676 AGGAAAUAUUGGUUGUCCU 12676 AGGAAAuAUUGGUUGUCCUdTsdT antis
    2282-2301 10677 GGACAACCAAUAUUUCCUG 12677 GGAcAAccAAuAuuuccuGdTsdT sense
    2282-2301 10678 CAGGAAAUAUUGGUUGUCC 12678 cAGGAAAuAUUGGUUGUCCdTsdT antis
    2317-2336 10679 UCAGUUGGUGGAAAUAAUA 12679 ucAGuuGGuGGAAAuAAuAdTsdT sense
    2317-2336 10680 UAUUAUUUCCACCAACUGA 12680 uAUuAUUUCcACcAACUGAdTsdT antis
    2346-2365 10681 GAACACCAACAAGGGAGCA 12681 GAAcAccAAcAAGGGAGcAdTsdT sense
    2346-2365 10682 UGCUCCCUUGUUGGUGUUC 12682 UGCUCCCUUGUUGGUGUUCdTsdT antis
    2401-2420 10683 AUUCCCUCAAAUCAAGGCA 12683 AuucccucAAAucAAGGcAdTsdT sense
    2401-2420 10684 UGCCUUGAUUUGAGGGAAU 12684 UGCCUUGAUUUGAGGGAAUdTsdT antis
    2402-2421 10685 UUCCCUCAAAUCAAGGCAC 12685 uucccucAAAucAAGGcAcdTsdT sense
    2402-2421 10686 GUGCCUUGAUUUGAGGGAA 12686 GUGCCUUGAUUUGAGGGAAdTsdT antis
    2463-2482 10687 CAAUUGCACUGUGCAGCCG 12687 cAAuuGcAcuGuGcAGccGdTsdT sense
    2463-2482 10688 CGGCUGCACAGUGCAAUUG 12688 CGGCUGcAcAGUGcAAUUGdTsdT antis
    1537-1556 10689 ACCGAGAACCACCUCCUUU 12689 AccGAGAAccAccuccuuudTsdT sense
    1537-1556 10690 AAAGGAGGUGGUUCUCGGU 12690 AAAGGAGGUGGUUCUCGGUdTsdT antis
    1554-1573 10691 UUGCGGAGAGCUGCAAGCC 12691 uuGcGGAGAGcuGcAAGccdTsdT sense
    1554-1573 10692 GGCUUGCAGCUCUCCGCAA 12692 GGCUUGcAGCUCUCCGcAAdTsdT antis
    1555-1574 10693 UGCGGAGAGCUGCAAGCCA 12693 uGcGGAGAGcuGcAAGccAdTsdT sense
    1555-1574 10694 UGGCUUGCAGCUCUCCGCA 12694 UGGCUUGcAGCUCUCCGcAdTsdT antis
    1562-1581 10695 AGCUGCAAGCCAGUGCAGC 12695 AGcuGcAAGccAGuGcAGcdTsdT sense
    1562-1581 10696 GCUGCACUGGCUUGCAGCU 12696 GCUGcACUGGCUUGcAGCUdTsdT antis
    1563-1582 10697 GCUGCAAGCCAGUGCAGCA 12697 GcuGcAAGccAGuGcAGcAdTsdT sense
    1563-1582 10698 UGCUGCACUGGCUUGCAGC 12698 UGCUGcACUGGCUUGcAGCdTsdT antis
    1570-1589 10699 GCCAGUGCAGCAGCCUUCA 12699 GccAGuGcAGcAGccuucAdTsdT sense
    1570-1589 10700 UGAAGGCUGCUGCACUGGC 12700 UGAAGGCUGCUGcACUGGCdTsdT antis
    1571-1590 10701 CCAGUGCAGCAGCCUUCAG 12701 ccAGuGcAGcAGccuucAGdTsdT sense
    1571-1590 10702 CUGAAGGCUGCUGCACUGG 12702 CUGAAGGCUGCUGcACUGGdTsdT antis
    1589-1608 10703 GCUUUUGGUAGCAUGAAAG 12703 GcuuuuGGuAGcAuGAAAGdTsdT sense
    1589-1608 10704 CUUUCAUGCUACCAAAAGC 12704 CUUUcAUGCuACcAAAAGCdTsdT antis
    1595-1614 10705 GGUAGCAUGAAAGUUAGCA 12705 GGuAGcAuGAAAGuuAGcAdTsdT sense
    1595-1614 10706 UGCUAACUUUCAUGCUACC 12706 UGCuAACUUUcAUGCuACCdTsdT antis
    1596-1615 10707 GUAGCAUGAAAGUUAGCAG 12707 GuAGcAuGAAAGuuAGcAGdTsdT sense
    1596-1615 10708 CUGCUAACUUUCAUGCUAC 12708 CUGCuAACUUUcAUGCuACdTsdT antis
    1597-1616 10709 UAGCAUGAAAGUUAGCAGA 12709 uAGcAuGAAAGuuAGcAGAdTsdT sense
    1597-1616 10710 UCUGCUAACUUUCAUGCUA 12710 UCUGCuAACUUUcAUGCuAdTsdT antis
    1606-1625 10711 AGUUAGCAGAGAUAAAGAU 12711 AGuuAGcAGAGAuAAAGAudTsdT sense
    1606-1625 10712 AUCUUUAUCUCUGCUAACU 12712 AUCUUuAUCUCUGCuAACUdTsdT antis
    1607-1626 10713 GUUAGCAGAGAUAAAGAUG 12713 GuuAGcAGAGAuAAAGAuGdTsdT sense
    1607-1626 10714 CAUCUUUAUCUCUGCUAAC 12714 cAUCUUuAUCUCUGCuAACdTsdT antis
    1608-1627 10715 UUAGCAGAGAUAAAGAUGG 12715 uuAGcAGAGAuAAAGAuGGdTsdT sense
    1608-1627 10716 CCAUCUUUAUCUCUGCUAA 12716 CcAUCUUuAUCUCUGCuAAdTsdT antis
    1616-1635 10717 GAUAAAGAUGGCAGCAAGG 12717 GAuAAAGAuGGcAGcAAGGdTsdT sense
    1616-1635 10718 CCUUGCUGCCAUCUUUAUC 12718 CCUUGCUGCcAUCUUuAUCdTsdT antis
    1617-1636 10719 AUAAAGAUGGCAGCAAGGU 12719 AuAAAGAuGGcAGcAAGGudTsdT sense
    1617-1636 10720 ACCUUGCUGCCAUCUUUAU 12720 ACCUUGCUGCcAUCUUuAUdTsdT antis
    1638-1657 10721 CCACAGUAGUGGCAACUCC 12721 ccAcAGuAGuGGcAAcuccdTsdT sense
    1638-1657 10722 GGAGUUGCCACUACUGUGG 12722 GGAGUUGCcACuACUGUGGdTsdT antis
    1647-1666 10723 UGGCAACUCCUGGCCAGGG 12723 uGGcAAcuccuGGccAGGGdTsdT sense
    1647-1666 10724 CCCUGGCCAGGAGUUGCCA 12724 CCCUGGCcAGGAGUUGCcAdTsdT antis
    1657-1676 10725 UGGCCAGGGUCCUGACAGG 12725 uGGccAGGGuccuGAcAGGdTsdT sense
    1657-1676 10726 CCUGUCAGGACCCUGGCCA 12726 CCUGUcAGGACCCUGGCcAdTsdT antis
    1660-1679 10727 CCAGGGUCCUGACAGGCCA 12727 ccAGGGuccuGAcAGGccAdTsdT sense
    1660-1679 10728 UGGCCUGUCAGGACCCUGG 12728 UGGCCUGUcAGGACCCUGGdTsdT antis
    1664-1683 10729 GGUCCUGACAGGCCACAGG 12729 GGuccuGAcAGGccAcAGGdTsdT sense
    1664-1683 10730 CCUGUGGCCUGUCAGGACC 12730 CCUGUGGCCUGUcAGGACCdTsdT antis
    1668-1687 10731 CUGACAGGCCACAGGAAGU 12731 cuGAcAGGccAcAGGAAGudTsdT sense
    1668-1687 10732 ACUUCCUGUGGCCUGUCAG 12732 ACUUCCUGUGGCCUGUcAGdTsdT antis
    1692-1711 10733 AUACAGACACGAAAGUGAU 12733 AuAcAGAcAcGAAAGuGAudTsdT sense
    1692-1711 10734 AUCACUUUCGUGUCUGUAU 12734 AUcACUUUCGUGUCUGuAUdTsdT antis
    1694-1713 10735 ACAGACACGAAAGUGAUUG 12735 AcAGAcAcGAAAGuGAuuGdTsdT sense
    1694-1713 10736 CAAUCACUUUCGUGUCUGU 12736 cAAUcACUUUCGUGUCUGUdTsdT antis
    1716-1735 10737 AUGGAUCAUUUGGUGUGGU 12737 AuGGAucAuuuGGuGuGGudTsdT sense
    1716-1735 10738 ACCACACCAAAUGAUCCAU 12738 ACcAcACcAAAUGAUCcAUdTsdT antis
    1730-1749 10739 GUGGUAUAUCAAGCCAAAC 12739 GuGGuAuAucAAGccAAAcdTsdT sense
    1730-1749 10740 GUUUGGCUUGAUAUACCAC 12740 GUUUGGCUUGAuAuACcACdTsdT antis
    1764-1783 10741 AACUGGUUGCCAUCAAGAA 12741 AAcuGGuuGccAucAAGAAdTsdT sense
    1764-1783 10742 UUCUUGAUGGCAACCAGUU 12742 UUCUUGAUGGcAACcAGUUdTsdT antis
    1765-1784 10743 ACUGGUUGCCAUCAAGAAA 12743 AcuGGuuGccAucAAGAAAdTsdT sense
    1765-1784 10744 UUUCUUGAUGGCAACCAGU 12744 UUUCUUGAUGGcAACcAGUdTsdT antis
    1766-1785 10745 CUGGUUGCCAUCAAGAAAG 12745 cuGGuuGccAucAAGAAAGdTsdT sense
    1766-1785 10746 CUUUCUUGAUGGCAACCAG 12746 CUUUCUUGAUGGcAACcAGdTsdT antis
    1771-1790 10747 UGCCAUCAAGAAAGUUCUA 12747 uGccAucAAGAAAGuucuAdTsdT sense
    1771-1790 10748 UAGAACUUUCUUGAUGGCA 12748 uAGAACUUUCUUGAUGGcAdTsdT antis
    1777-1796 10749 CAAGAAAGUUCUACAGGAC 12749 cAAGAAAGuucuAcAGGAcdTsdT sense
    1777-1796 10750 GUCCUGUAGAACUUUCUUG 12750 GUCCUGuAGAACUUUCUUGdTsdT antis
    1811-1830 10751 CGAGAGCUCCAGAUCAUGA 12751 cGAGAGcuccAGAucAuGAdTsdT sense
    1811-1830 10752 UCAUGAUCUGGAGCUCUCG 12752 UcAUGAUCUGGAGCUCUCGdTsdT antis
    1814-1833 10753 GAGCUCCAGAUCAUGAGAA 12753 GAGcuccAGAucAuGAGAAdTsdT sense
    1814-1833 10754 UUCUCAUGAUCUGGAGCUC 12754 UUCUcAUGAUCUGGAGCUCdTsdT antis
    1835-1854 10755 CUAGACCACUGUAACAUAG 12755 cuAGAccAcuGuAAcAuAGdTsdT sense
    1835-1854 10756 CUAUGUUACAGUGGUCUAG 12756 CuAUGUuAcAGUGGUCuAGdTsdT antis
    1881-1900 10757 GUGGUGAGAAGAAAGAUGA 12757 GuGGuGAGAAGAAAGAuGAdTsdT sense
    1881-1900 10758 UCAUCUUUCUUCUCACCAC 12758 UcAUCUUUCUUCUcACcACdTsdT antis
    1882-1901 10759 UGGUGAGAAGAAAGAUGAG 12759 uGGuGAGAAGAAAGAuGAGdTsdT sense
    1882-1901 10760 CUCAUCUUUCUUCUCACCA 12760 CUcAUCUUUCUUCUcACcAdTsdT antis
    1902-1921 10761 UCUACCUUAACCUGGUGCU 12761 ucuAccuuAAccuGGuGcudTsdT sense
    1902-1921 10762 AGCACCAGGUUAAGGUAGA 12762 AGcACcAGGUuAAGGuAGAdTsdT antis
    1914-1933 10763 UGGUGCUGGACUAUGUUCC 12763 uGGuGcuGGAcuAuGuuccdTsdT sense
    1914-1933 10764 GGAACAUAGUCCAGCACCA 12764 GGAAcAuAGUCcAGcACcAdTsdT antis
    1932-1951 10765 CGGAGACAGUGUACAGAGU 12765 cGGAGAcAGuGuAcAGAGudTsdT sense
    1932-1951 10766 ACUCUGUACACUGUCUCCG 12766 ACUCUGuAcACUGUCUCCGdTsdT antis
    1968-1987 10767 GAGCCAAGCAGACACUCCC 12767 GAGccAAGcAGAcAcucccdTsdT sense
    1968-1987 10768 GGGAGUGUCUGCUUGGCUC 12768 GGGAGUGUCUGCUUGGCUCdTsdT antis
    1969-1988 10769 AGCCAAGCAGACACUCCCU 12769 AGccAAGcAGAcAcucccudTsdT sense
    1969-1988 10770 AGGGAGUGUCUGCUUGGCU 12770 AGGGAGUGUCUGCUUGGCUdTsdT antis
    1976-1995 10771 CAGACACUCCCUGUGAUCU 12771 cAGAcAcucccuGuGAucudTsdT sense
    1976-1995 10772 AGAUCACAGGGAGUGUCUG 12772 AGAUcAcAGGGAGUGUCUGdTsdT antis
    2002-2021 10773 GUUGUAUAUGUAUCAGCUG 12773 GuuGuAuAuGuAucAGcuGdTsdT sense
    2002-2021 10774 CAGCUGAUACAUAUACAAC 12774 cAGCUGAuAcAuAuAcAACdTsdT antis
    2013-2032 10775 AUCAGCUGUUCAGAAGUCU 12775 AucAGcuGuucAGAAGucudTsdT sense
    2013-2032 10776 AGACUUCUGAACAGCUGAU 12776 AGACUUCUGAAcAGCUGAUdTsdT antis
    2014-2033 10777 UCAGCUGUUCAGAAGUCUA 12777 ucAGcuGuucAGAAGucuAdTsdT sense
    2014-2033 10778 UAGACUUCUGAACAGCUGA 12778 uAGACUUCUGAAcAGCUGAdTsdT antis
    2032-2051 10779 AGCCUAUAUCCAUUCCUUU 12779 AGccuAuAuccAuuccuuudTsdT sense
    2032-2051 10780 AAAGGAAUGGAUAUAGGCU 12780 AAAGGAAUGGAuAuAGGCUdTsdT antis
    2033-2052 10781 GCCUAUAUCCAUUCCUUUG 12781 GccuAuAuccAuuccuuuGdTsdT sense
    2033-2052 10782 CAAAGGAAUGGAUAUAGGC 12782 cAAAGGAAUGGAuAuAGGCdTsdT antis
    2034-2053 10783 CCUAUAUCCAUUCCUUUGG 12783 ccuAuAuccAuuccuuuGGdTsdT sense
    2034-2053 10784 CCAAAGGAAUGGAUAUAGG 12784 CcAAAGGAAUGGAuAuAGGdTsdT antis
    2037-2056 10785 AUAUCCAUUCCUUUGGAAU 12785 AuAuccAuuccuuuGGAAudTsdT sense
    2037-2056 10786 AUUCCAAAGGAAUGGAUAU 12786 AUUCcAAAGGAAUGGAuAUdTsdT antis
    2038-2057 10787 UAUCCAUUCCUUUGGAAUC 12787 uAuccAuuccuuuGGAAucdTsdT sense
    2038-2057 10788 GAUUCCAAAGGAAUGGAUA 12788 GAUUCcAAAGGAAUGGAuAdTsdT antis
    2041-2060 10789 CCAUUCCUUUGGAAUCUGC 12789 ccAuuccuuuGGAAucuGcdTsdT sense
    2041-2060 10790 GCAGAUUCCAAAGGAAUGG 12790 GcAGAUUCcAAAGGAAUGGdTsdT antis
    2045-2064 10791 UCCUUUGGAAUCUGCCAUC 12791 uccuuuGGAAucuGccAucdTsdT sense
    2045-2064 10792 GAUGGCAGAUUCCAAAGGA 12792 GAUGGcAGAUUCcAAAGGAdTsdT antis
    2069-2088 10793 AUUAAACCACAGAACCUCU 12793 AuuAAAccAcAGAAccucudTsdT sense
    2069-2088 10794 AGAGGUUCUGUGGUUUAAU 12794 AGAGGUUCUGUGGUUuAAUdTsdT antis
    2110-2129 10795 AUUAAAACUCUGUGACUUU 12795 AuuAAAAcucuGuGAcuuudTsdT sense
    2110-2129 10796 AAAGUCACAGAGUUUUAAU 12796 AAAGUcAcAGAGUUUuAAUdTsdT antis
    2111-2130 10797 UUAAAACUCUGUGACUUUG 12797 uuAAAAcucuGuGAcuuuGdTsdT sense
    2111-2130 10798 CAAAGUCACAGAGUUUUAA 12798 cAAAGUcAcAGAGUUUuAAdTsdT antis
    2114-2133 10799 AAACUCUGUGACUUUGGAA 12799 AAAcucuGuGAcuuuGGAAdTsdT sense
    2114-2133 10800 UUCCAAAGUCACAGAGUUU 12800 UUCcAAAGUcAcAGAGUUUdTsdT antis
    2121-2140 10801 GUGACUUUGGAAGUGCAAA 12801 GuGAcuuuGGAAGuGcAAAdTsdT sense
    2121-2140 10802 UUUGCACUUCCAAAGUCAC 12802 UUUGcACUUCcAAAGUcACdTsdT antis
    2122-2141 10803 UGACUUUGGAAGUGCAAAG 12803 uGAcuuuGGAAGuGcAAAGdTsdT sense
    2122-2141 10804 CUUUGCACUUCCAAAGUCA 12804 CUUUGcACUUCcAAAGUcAdTsdT antis
    2127-2146 10805 UUGGAAGUGCAAAGCAGCU 12805 uuGGAAGuGcAAAGcAGcudTsdT sense
    2127-2146 10806 AGCUGCUUUGCACUUCCAA 12806 AGCUGCUUUGcACUUCcAAdTsdT antis
    2128-2147 10807 UGGAAGUGCAAAGCAGCUG 12807 uGGAAGuGcAAAGcAGcuGdTsdT sense
    2128-2147 10808 CAGCUGCUUUGCACUUCCA 12808 cAGCUGCUUUGcACUUCcAdTsdT antis
    2130-2149 10809 GAAGUGCAAAGCAGCUGGU 12809 GAAGuGcAAAGcAGcuGGudTsdT sense
    2130-2149 10810 ACCAGCUGCUUUGCACUUC 12810 ACcAGCUGCUUUGcACUUCdTsdT antis
    2144-2163 10811 CUGGUCCGAGGAGAGCCCA 12811 cuGGuccGAGGAGAGcccAdTsdT sense
    2144-2163 10812 UGGGCUCUCCUCGGACCAG 12812 UGGGCUCUCCUCGGACcAGdTsdT antis
    2145-2164 10813 UGGUCCGAGGAGAGCCCAA 12813 uGGuccGAGGAGAGcccAAdTsdT sense
    2145-2164 10814 UUGGGCUCUCCUCGGACCA 12814 UUGGGCUCUCCUCGGACcAdTsdT antis
    2152-2171 10815 AGGAGAGCCCAAUGUUUCA 12815 AGGAGAGcccAAuGuuucAdTsdT sense
    2152-2171 10816 UGAAACAUUGGGCUCUCCU 12816 UGAAAcAUUGGGCUCUCCUdTsdT antis
    2173-2192 10817 UAUCUGUUCUCGGUACUAC 12817 uAucuGuucucGGuAcuAcdTsdT sense
    2173-2192 10818 GUAGUACCGAGAACAGAUA 12818 GuAGuACCGAGAAcAGAuAdTsdT antis
    2244-2263 10819 UAUGGUCUGCAGGCUGUGU 12819 uAuGGucuGcAGGcuGuGudTsdT sense
    2244-2263 10820 ACACAGCCUGCAGACCAUA 12820 AcAcAGCCUGcAGACcAuAdTsdT antis
    2293-2312 10821 AUUUCCUGGGGACAGUGGU 12821 AuuuccuGGGGAcAGuGGudTsdT sense
    2293-2312 10822 ACCACUGUCCCCAGGAAAU 12822 ACcACUGUCCCcAGGAAAUdTsdT antis
    2296-2315 10823 UCCUGGGGACAGUGGUGUG 12823 uccuGGGGAcAGuGGuGuGdTsdT sense
    2296-2315 10824 CACACCACUGUCCCCAGGA 12824 cAcACcACUGUCCCcAGGAdTsdT antis
    2297-2316 10825 CCUGGGGACAGUGGUGUGG 12825 ccuGGGGAcAGuGGuGuGGdTsdT sense
    2297-2316 10826 CCACACCACUGUCCCCAGG 12826 CcAcACcACUGUCCCcAGGdTsdT antis
    2320-2339 10827 GUUGGUGGAAAUAAUAAAG 12827 GuuGGuGGAAAuAAuAAAGdTsdT sense
    2320-2339 10828 CUUUAUUAUUUCCACCAAC 12828 CUUuAUuAUUUCcACcAACdTsdT antis
    2321-2340 10829 UUGGUGGAAAUAAUAAAGG 12829 uuGGuGGAAAuAAuAAAGGdTsdT sense
    2321-2340 10830 CCUUUAUUAUUUCCACCAA 12830 CCUUuAUuAUUUCcACcAAdTsdT antis
    2322-2341 10831 UGGUGGAAAUAAUAAAGGU 12831 uGGuGGAAAuAAuAAAGGudTsdT sense
    2322-2341 10832 ACCUUUAUUAUUUCCACCA 12832 ACCUUuAUuAUUUCcACcAdTsdT antis
    2348-2367 10833 ACACCAACAAGGGAGCAAA 12833 AcAccAAcAAGGGAGcAAAdTsdT sense
    2348-2367 10834 UUUGCUCCCUUGUUGGUGU 12834 UUUGCUCCCUUGUUGGUGUdTsdT antis
    2349-2368 10835 CACCAACAAGGGAGCAAAU 12835 cAccAAcAAGGGAGcAAAudTsdT sense
    2349-2368 10836 AUUUGCUCCCUUGUUGGUG 12836 AUUUGCUCCCUUGUUGGUGdTsdT antis
    2389-2408 10837 UACAGAAUUCAAAUUCCCU 12837 uAcAGAAuucAAAuucccudTsdT sense
    2389-2408 10838 AGGGAAUUUGAAUUCUGUA 12838 AGGGAAUUUGAAUUCUGuAdTsdT antis
    2414-2433 10839 AAGGCACAUCCUUGGACAA 12839 AAGGcAcAuccuuGGAcAAdTsdT sense
    2414-2433 10840 UUGUCCAAGGAUGUGCCUU 12840 UUGUCcAAGGAUGUGCCUUdTsdT antis
    2419-2438 10841 ACAUCCUUGGACAAAGGUC 12841 AcAuccuuGGAcAAAGGucdTsdT sense
    2419-2438 10842 GACCUUUGUCCAAGGAUGU 12842 GACCUUUGUCcAAGGAUGUdTsdT antis
    2429-2448 10843 ACAAAGGUCUUCCGGCCCC 12843 AcAAAGGucuuccGGccccdTsdT sense
    2429-2448 10844 GGGGCCGGAAGACCUUUGU 12844 GGGGCCGGAAGACCUUUGUdTsdT antis
    2460-2479 10845 AGGCAAUUGCACUGUGCAG 12845 AGGcAAuuGcAcuGuGcAGdTsdT sense
    2460-2479 10846 CUGCACAGUGCAAUUGCCU 12846 CUGcAcAGUGcAAUUGCCUdTsdT antis
    2474-2493 10847 UGCAGCCGUCUGCUGGAGU 12847 uGcAGccGucuGcuGGAGudTsdT sense
    2474-2493 10848 ACUCCAGCAGACGGCUGCA 12848 ACUCcAGcAGACGGCUGcAdTsdT antis
    2480-2499 10849 CGUCUGCUGGAGUACACAC 12849 cGucuGcuGGAGuAcAcAcdTsdT sense
    2480-2499 10850 GUGUGUACUCCAGCAGACG 12850 GUGUGuACUCcAGcAGACGdTsdT antis
    2481-2500 10851 GUCUGCUGGAGUACACACC 12851 GucuGcuGGAGuAcAcAccdTsdT sense
    2481-2500 10852 GGUGUGUACUCCAGCAGAC 12852 GGUGUGuACUCcAGcAGACdTsdT antis
    2511-2530 10853 UAACACCACUGGAAGCUUG 12853 uAAcAccAcuGGAAGcuuGdTsdT sense
    2511-2530 10854 CAAGCUUCCAGUGGUGUUA 12854 cAAGCUUCcAGUGGUGUuAdTsdT antis
    1540-1559 10855 GAGAACCACCUCCUUUGCG 12855 GAGAAccAccuccuuuGcGdTsdT sense
    1540-1559 10856 CGCAAAGGAGGUGGUUCUC 12856 CGcAAAGGAGGUGGUUCUCdTsdT antis
    1883-1902 10857 GGUGAGAAGAAAGAUGAGG 12857 GGuGAGAAGAAAGAuGAGGdTsdT sense
    1883-1902 10858 CCUCAUCUUUCUUCUCACC 12858 CCUcAUCUUUCUUCUcACCdTsdT antis
    2044-2063 10859 UUCCUUUGGAAUCUGCCAU 12859 uuccuuuGGAAucuGccAudTsdT sense
    2044-2063 10860 AUGGCAGAUUCCAAAGGAA 12860 AUGGcAGAUUCcAAAGGAAdTsdT antis
    2205-2224 10861 UGAUCUUUGGAGCCACUGA 12861 uGAucuuuGGAGccAcuGAdTsdT sense
    2205-2224 10862 UCAGUGGCUCCAAAGAUCA 12862 UcAGUGGCUCcAAAGAUcAdTsdT antis
    2331-2350 10863 UAAUAAAGGUCCUAGGAAC 12863 uAAuAAAGGuccuAGGAAcdTsdT sense
    2331-2350 10864 GUUCCUAGGACCUUUAUUA 12864 GUUCCuAGGACCUUuAUuAdTsdT antis
    2384-2403 10865 AAUUAUACAGAAUUCAAAU 12865 AAuuAuAcAGAAuucAAAudTsdT sense
    2384-2403 10866 AUUUGAAUUCUGUAUAAUU 12866 AUUUGAAUUCUGuAuAAUUdTsdT antis
    1557-1576 10867 CGGAGAGCUGCAAGCCAGU 12867 cGGAGAGcuGcAAGccAGudTsdT sense
    1557-1576 10868 ACUGGCUUGCAGCUCUCCG 12868 ACUGGCUUGcAGCUCUCCGdTsdT antis
    1567-1586 10869 CAAGCCAGUGCAGCAGCCU 12869 cAAGccAGuGcAGcAGccudTsdT sense
    1567-1586 10870 AGGCUGCUGCACUGGCUUG 12870 AGGCUGCUGcACUGGCUUGdTsdT antis
    1568-1587 10871 AAGCCAGUGCAGCAGCCUU 12871 AAGccAGuGcAGcAGccuudTsdT sense
    1568-1587 10872 AAGGCUGCUGCACUGGCUU 12872 AAGGCUGCUGcACUGGCUUdTsdT antis
    1580-1599 10873 CAGCCUUCAGCUUUUGGUA 12873 cAGccuucAGcuuuuGGuAdTsdT sense
    1580-1599 10874 UACCAAAAGCUGAAGGCUG 12874 uACcAAAAGCUGAAGGCUGdTsdT antis
    1583-1602 10875 CCUUCAGCUUUUGGUAGCA 12875 ccuucAGcuuuuGGuAGcAdTsdT sense
    1583-1602 10876 UGCUACCAAAAGCUGAAGG 12876 UGCuACcAAAAGCUGAAGGdTsdT antis
    1590-1609 10877 CUUUUGGUAGCAUGAAAGU 12877 cuuuuGGuAGcAuGAAAGudTsdT sense
    1590-1609 10878 ACUUUCAUGCUACCAAAAG 12878 ACUUUcAUGCuACcAAAAGdTsdT antis
    1609-1628 10879 UAGCAGAGAUAAAGAUGGC 12879 uAGcAGAGAuAAAGAuGGcdTsdT sense
    1609-1628 10880 GCCAUCUUUAUCUCUGCUA 12880 GCcAUCUUuAUCUCUGCuAdTsdT antis
    1615-1634 10881 AGAUAAAGAUGGCAGCAAG 12881 AGAuAAAGAuGGcAGcAAGdTsdT sense
    1615-1634 10882 CUUGCUGCCAUCUUUAUCU 12882 CUUGCUGCcAUCUUuAUCUdTsdT antis
    1655-1674 10883 CCUGGCCAGGGUCCUGACA 12883 ccuGGccAGGGuccuGAcAdTsdT sense
    1655-1674 10884 UGUCAGGACCCUGGCCAGG 12884 UGUcAGGACCCUGGCcAGGdTsdT antis
    1671-1690 10885 ACAGGCCACAGGAAGUCAG 12885 AcAGGccAcAGGAAGucAGdTsdT sense
    1671-1690 10886 CUGACUUCCUGUGGCCUGU 12886 CUGACUUCCUGUGGCCUGUdTsdT antis
    1672-1691 10887 CAGGCCACAGGAAGUCAGU 12887 cAGGccAcAGGAAGucAGudTsdT sense
    1672-1691 10888 ACUGACUUCCUGUGGCCUG 12888 ACUGACUUCCUGUGGCCUGdTsdT antis
    1747-1766 10889 ACUUUGUGAUUCUGGAGAA 12889 AcuuuGuGAuucuGGAGAAdTsdT sense
    1747-1766 10890 UUCUCCAGAAUCACAAAGU 12890 UUCUCcAGAAUcAcAAAGUdTsdT antis
    1748-1767 10891 CUUUGUGAUUCUGGAGAAC 12891 cuuuGuGAuucuGGAGAAcdTsdT sense
    1748-1767 10892 GUUCUCCAGAAUCACAAAG 12892 GUUCUCcAGAAUcAcAAAGdTsdT antis
    1750-1769 10893 UUGUGAUUCUGGAGAACUG 12893 uuGuGAuucuGGAGAAcuGdTsdT sense
    1750-1769 10894 CAGUUCUCCAGAAUCACAA 12894 cAGUUCUCcAGAAUcAcAAdTsdT antis
    1751-1770 10895 UGUGAUUCUGGAGAACUGG 12895 uGuGAuucuGGAGAAcuGGdTsdT sense
    1751-1770 10896 CCAGUUCUCCAGAAUCACA 12896 CcAGUUCUCcAGAAUcAcAdTsdT antis
    1752-1771 10897 GUGAUUCUGGAGAACUGGU 12897 GuGAuucuGGAGAAcuGGudTsdT sense
    1752-1771 10898 ACCAGUUCUCCAGAAUCAC 12898 ACcAGUUCUCcAGAAUcACdTsdT antis
    1753-1772 10899 UGAUUCUGGAGAACUGGUU 12899 uGAuucuGGAGAAcuGGuudTsdT sense
    1753-1772 10900 AACCAGUUCUCCAGAAUCA 12900 AACcAGUUCUCcAGAAUcAdTsdT antis
    2117-2136 10901 CUCUGUGACUUUGGAAGUG 12901 cucuGuGAcuuuGGAAGuGdTsdT sense
    2117-2136 10902 CACUUCCAAAGUCACAGAG 12902 cACUUCcAAAGUcAcAGAGdTsdT antis
    2118-2137 10903 UCUGUGACUUUGGAAGUGC 12903 ucuGuGAcuuuGGAAGuGcdTsdT sense
    2118-2137 10904 GCACUUCCAAAGUCACAGA 12904 GcACUUCcAAAGUcAcAGAdTsdT antis
    2148-2167 10905 UCCGAGGAGAGCCCAAUGU 12905 uccGAGGAGAGcccAAuGudTsdT sense
    2148-2167 10906 ACAUUGGGCUCUCCUCGGA 12906 AcAUUGGGCUCUCCUCGGAdTsdT antis
    2202-2221 10907 AGUUGAUCUUUGGAGCCAC 12907 AGuuGAucuuuGGAGccAcdTsdT sense
    2202-2221 10908 GUGGCUCCAAAGAUCAACU 12908 GUGGCUCcAAAGAUcAACUdTsdT antis
    2203-2222 10909 GUUGAUCUUUGGAGCCACU 12909 GuuGAucuuuGGAGccAcudTsdT sense
    2203-2222 10910 AGUGGCUCCAAAGAUCAAC 12910 AGUGGCUCcAAAGAUcAACdTsdT antis
    2204-2223 10911 UUGAUCUUUGGAGCCACUG 12911 uuGAucuuuGGAGccAcuGdTsdT sense
    2204-2223 10912 CAGUGGCUCCAAAGAUCAA 12912 cAGUGGCUCcAAAGAUcAAdTsdT antis
    2206-2225 10913 GAUCUUUGGAGCCACUGAU 12913 GAucuuuGGAGccAcuGAudTsdT sense
    2206-2225 10914 AUCAGUGGCUCCAAAGAUC 12914 AUcAGUGGCUCcAAAGAUCdTsdT antis
    2245-2264 10915 AUGGUCUGCAGGCUGUGUG 12915 AuGGucuGcAGGcuGuGuGdTsdT sense
    2245-2264 10916 CACACAGCCUGCAGACCAU 12916 cAcAcAGCCUGcAGACcAUdTsdT antis
    2252-2271 10917 GCAGGCUGUGUGUUGGCUG 12917 GcAGGcuGuGuGuuGGcuGdTsdT sense
    2252-2271 10918 CAGCCAACACACAGCCUGC 12918 cAGCcAAcAcAcAGCCUGCdTsdT antis
    2266-2285 10919 GGCUGAAUUGUUGCUAGGA 12919 GGcuGAAuuGuuGcuAGGAdTsdT sense
    2266-2285 10920 UCCUAGCAACAAUUCAGCC 12920 UCCuAGcAAcAAUUcAGCCdTsdT antis
    2294-2313 10921 UUUCCUGGGGACAGUGGUG 12921 uuuccuGGGGAcAGuGGuGdTsdT sense
    2294-2313 10922 CACCACUGUCCCCAGGAAA 12922 cACcACUGUCCCcAGGAAAdTsdT antis
    2295-2314 10923 UUCCUGGGGACAGUGGUGU 12923 uuccuGGGGAcAGuGGuGudTsdT sense
    2295-2314 10924 ACACCACUGUCCCCAGGAA 12924 AcACcACUGUCCCcAGGAAdTsdT antis
    2350-2369 10925 ACCAACAAGGGAGCAAAUU 12925 AccAAcAAGGGAGcAAAuudTsdT sense
    2350-2369 10926 AAUUUGCUCCCUUGUUGGU 12926 AAUUUGCUCCCUUGUUGGUdTsdT antis
    2382-2401 10927 CAAAUUAUACAGAAUUCAA 12927 cAAAuuAuAcAGAAuucAAdTsdT sense
    2382-2401 10928 UUGAAUUCUGUAUAAUUUG 12928 UUGAAUUCUGuAuAAUUUGdTsdT antis
    1543-1562 10929 AACCACCUCCUUUGCGGAG 12929 AAccAccuccuuuGcGGAGdTsdT sense
    1543-1562 10930 CUCCGCAAAGGAGGUGGUU 12930 CUCCGcAAAGGAGGUGGUUdTsdT antis
    1544-1563 10931 ACCACCUCCUUUGCGGAGA 12931 AccAccuccuuuGcGGAGAdTsdT sense
    1544-1563 10932 UCUCCGCAAAGGAGGUGGU 12932 UCUCCGcAAAGGAGGUGGUdTsdT antis
    1545-1564 10933 CCACCUCCUUUGCGGAGAG 12933 ccAccuccuuuGcGGAGAGdTsdT sense
    1545-1564 10934 CUCUCCGCAAAGGAGGUGG 12934 CUCUCCGcAAAGGAGGUGGdTsdT antis
    1712-1731 10935 GGAAAUGGAUCAUUUGGUG 12935 GGAAAuGGAucAuuuGGuGdTsdT sense
    1712-1731 10936 CACCAAAUGAUCCAUUUCC 12936 cACcAAAUGAUCcAUUUCCdTsdT antis
    1879-1898 10937 GAGUGGUGAGAAGAAAGAU 12937 GAGuGGuGAGAAGAAAGAudTsdT sense
    1879-1898 10938 AUCUUUCUUCUCACCACUC 12938 AUCUUUCUUCUcACcACUCdTsdT antis
    2060-2079 10939 CAUCGAGACAUUAAACCAC 12939 cAucGAGAcAuuAAAccAcdTsdT sense
    2060-2079 10940 GUGGUUUAAUGUCUCGAUG 12940 GUGGUUuAAUGUCUCGAUGdTsdT antis
    2062-2081 10941 UCGAGACAUUAAACCACAG 12941 ucGAGAcAuuAAAccAcAGdTsdT sense
    2062-2081 10942 CUGUGGUUUAAUGUCUCGA 12942 CUGUGGUUuAAUGUCUCGAdTsdT antis
    2061-2080 10943 AUCGAGACAUUAAACCACA 12943 AucGAGAcAuuAAAccAcAdTsdT sense
    2061-2080 10944 UGUGGUUUAAUGUCUCGAU 12944 UGUGGUUuAAUGUCUCGAUdTsdT antis
    2058-2077 10945 GCCAUCGAGACAUUAAACC 12945 GccAucGAGAcAuuAAAccdTsdT sense
    2058-2077 10946 GGUUUAAUGUCUCGAUGGC 12946 GGUUuAAUGUCUCGAUGGCdTsdT antis
    2059-2078 10947 CCAUCGAGACAUUAAACCA 12947 ccAucGAGAcAuuAAAccAdTsdT sense
    2059-2078 10948 UGGUUUAAUGUCUCGAUGG 12948 UGGUUuAAUGUCUCGAUGGdTsdT antis
    1639-1658 10949 CACAGUAGUGGCAACUCCU 12949 cAcAGuAGuGGcAAcuccudTsdT sense
    1639-1658 10950 AGGAGUUGCCACUACUGUG 12950 AGGAGUUGCcACuACUGUGdTsdT antis
    2064-2083 10951 GAGACAUUAAACCACAGAA 12951 GAGAcAuuAAAccAcAGAAdTsdT sense
    2064-2083 10952 UUCUGUGGUUUAAUGUCUC 12952 UUCUGUGGUUuAAUGUCUCdTsdT antis
    1641-1660 10953 CAGUAGUGGCAACUCCUGG 12953 cAGuAGuGGcAAcuccuGGdTsdT sense
    1641-1660 10954 CCAGGAGUUGCCACUACUG 12954 CcAGGAGUUGCcACuACUGdTsdT antis
    1812-1831 10955 GAGAGCUCCAGAUCAUGAG 12955 GAGAGcuccAGAucAuGAGdTsdT sense
    1812-1831 10956 CUCAUGAUCUGGAGCUCUC 12956 CUcAUGAUCUGGAGCUCUCdTsdT antis
    2063-2082 10957 CGAGACAUUAAACCACAGA 12957 cGAGAcAuuAAAccAcAGAdTsdT sense
    2063-2082 10958 UCUGUGGUUUAAUGUCUCG 12958 UCUGUGGUUuAAUGUCUCGdTsdT antis
    2065-2084 10959 AGACAUUAAACCACAGAAC 12959 AGAcAuuAAAccAcAGAAcdTsdT sense
    2065-2084 10960 GUUCUGUGGUUUAAUGUCU 12960 GUUCUGUGGUUuAAUGUCUdTsdT antis
    2112-2131 10961 UAAAACUCUGUGACUUUGG 12961 uAAAAcucuGuGAcuuuGGdTsdT sense
    2112-2131 10962 CCAAAGUCACAGAGUUUUA 12962 CcAAAGUcAcAGAGUUUuAdTsdT antis
    2119-2138 10963 CUGUGACUUUGGAAGUGCA 12963 cuGuGAcuuuGGAAGuGcAdTsdT sense
    2119-2138 10964 UGCACUUCCAAAGUCACAG 12964 UGcACUUCcAAAGUcAcAGdTsdT antis
    2123-2142 10965 GACUUUGGAAGUGCAAAGC 12965 GAcuuuGGAAGuGcAAAGcdTsdT sense
    2123-2142 10966 GCUUUGCACUUCCAAAGUC 12966 GCUUUGcACUUCcAAAGUCdTsdT antis
    2131-2150 10967 AAGUGCAAAGCAGCUGGUC 12967 AAGuGcAAAGcAGcuGGucdTsdT sense
    2131-2150 10968 GACCAGCUGCUUUGCACUU 12968 GACcAGCUGCUUUGcACUUdTsdT antis
    1715-1734 10969 AAUGGAUCAUUUGGUGUGG 12969 AAuGGAucAuuuGGuGuGGdTsdT sense
    1715-1734 10970 CCACACCAAAUGAUCCAUU 12970 CcAcACcAAAUGAUCcAUUdTsdT antis
    2482-2501 10971 UCUGCUGGAGUACACACCU 12971 ucuGcuGGAGuAcAcAccudTsdT sense
    2482-2501 10972 AGGUGUGUACUCCAGCAGA 12972 AGGUGUGuACUCcAGcAGAdTsdT antis
    1714-1733 10973 AAAUGGAUCAUUUGGUGUG 12973 AAAuGGAucAuuuGGuGuGdTsdT sense
    1714-1733 10974 CACACCAAAUGAUCCAUUU 12974 cAcACcAAAUGAUCcAUUUdTsdT antis
    1884-1903 10975 GUGAGAAGAAAGAUGAGGU 12975 GuGAGAAGAAAGAuGAGGudTsdT sense
    1884-1903 10976 ACCUCAUCUUUCUUCUCAC 12976 ACCUcAUCUUUCUUCUcACdTsdT antis
    2039-2058 10977 AUCCAUUCCUUUGGAAUCU 12977 AuccAuuccuuuGGAAucudTsdT sense
    2039-2058 10978 AGAUUCCAAAGGAAUGGAU 12978 AGAUUCcAAAGGAAUGGAUdTsdT antis
    2113-2132 10979 AAAACUCUGUGACUUUGGA 12979 AAAAcucuGuGAcuuuGGAdTsdT sense
    2113-2132 10980 UCCAAAGUCACAGAGUUUU 12980 UCcAAAGUcAcAGAGUUUUdTsdT antis
    2246-2265 10981 UGGUCUGCAGGCUGUGUGU 12981 uGGucuGcAGGcuGuGuGudTsdT sense
    2246-2265 10982 ACACACAGCCUGCAGACCA 12982 AcAcAcAGCCUGcAGACcAdTsdT antis
    1713-1732 10983 GAAAUGGAUCAUUUGGUGU 12983 GAAAuGGAucAuuuGGuGudTsdT sense
    1713-1732 10984 ACACCAAAUGAUCCAUUUC 12984 AcACcAAAUGAUCcAUUUCdTsdT antis
  • TABLE 4
    Sequences of duplexes targeting Mouse GSK3-alpha
    Target sequence start identifies first nucleotide in target sequence in mouse
    GSK3-alpha mRNA NM_001031667.1. Unmodified sense strand is identical to target
    sequence. Unmodified antisense strand is complementary to target sequence.
    Target
    sequence SEQ ID unmodified sense strand SEQ unmodified antisense strand
    Duplex start NO: 5′ to 3′ ID NO: 5′ to 3′
    AD-18821 670 12985 AACUGCAGAUUAUGCGUAA 12996 UUACGCAUAAUCUGCAGUU
    AD-18823 330 12986 GGCGGCGGGAAAGCGUCAG 12997 CUGACGCUUUCCCGCCGCC
    AD-18824 239 12987 GGCGCGGACCAGCUCGUUC 12998 GAACGAGCUGGUCCGCGCC
    AD-18825 1340 12988 CCUACUGGAGUACACGCCA 12999 UGGCGUGUACUCCAGUAGG
    AD-18826 1342 12989 UACUGGAGUACACGCCAUC 13000 GAUGGCGUGUACUCCAGUA
    AD-18827 1073 12990 CACAGAUUACACCUCGUCC 13001 GGACGAGGUGUAAUCUGUG
    AD-18828 1236 12991 CCUAACUAUACGGAGUUCA 13002 UGAACUCCGUAUAGUUAGG
    AD-18829 435 12992 GCGGGCACUAGCUUCCCGC 13003 GCGGGAAGCUAGUGCCCGC
    AD-18830 1231 12993 UGAACCCUAACUAUACGGA 13004 UCCGUAUAGUUAGGGUUCA
    AD-18831 1234 12994 ACCCUAACUAUACGGAGUU 13005 AACUCCGUAUAGUUAGGGU
    AD-18832 1235 12995 CCCUAACUAUACGGAGUUC 13006 GAACUCCGUAUAGUUAGGG
    Target SEQ
    sequence ID modified sense strand SEQ ID modified antisense strand
    Duplex start NO: 5′ to 3′ NO: 5′ to 3′
    AD-18821-b1 670 13007 AAcuGcAGAuuAuGcGuAAdTsdT 13018 UuACGcAuAAUCUGcAGUUdTsdT
    AD-18823-b1 330 13008 GGcGGcGGGAAAGcGucAGdTsdT 13019 CUGACGCUUUCCCGCCGCCdTsdT
    AD-18824-b1 239 13009 GGcGcGGAccAGcucGuucdTsdT 13020 GAACGAGCUGGUCCGCGCCdTsdT
    AD-18825-b1 1340 13010 ccuAcuGGAGuAcAcGccAdTsdT 13021 UGGCGUGuACUCcAGuAGGdTsdT
    AD-18826-b1 1342 13011 uAcuGGAGuAcAcGccAucdTsdT 13022 GAUGGCGUGuACUCcAGuAdTsdT
    AD-18827-b1 1073 13012 cAcAGAuuAcAccucGuccdTsdT 13023 GGACGAGGUGuAAUCUGUGdTsdT
    AD-18828-b1 1236 13013 ccuAAcuAuAcGGAGuucAdTsdT 13024 UGAACUCCGuAuAGUuAGGdTsdT
    AD-18829-b1 435 13014 GcGGGcAcuAGcuucccGcdTsdT 13025 GCGGGAAGCuAGUGCCCGCdTsdT
    AD-18830-b1 1231 13015 uGAAcccuAAcuAuAcGGAdTsdT 13026 UCCGuAuAGUuAGGGUUcAdTsdT
    AD-18831-b1 1234 13016 AcccuAAcuAuAcGGAGuudTsdT 13027 AACUCCGuAuAGUuAGGGUdTsdT
    AD-18832-b1 1235 13017 cccuAAcuAuAcGGAGuucdTsdT 13028 GAACUCCGuAuAGUuAGGGdTsdT
  • TABLE 5
    Sequences of duplexes targeting Mouse GSK3-beta
    Target sequence start identifies first nucleotide in target sequence in mouse
    GSK3-beta mRNA NM_019827.6. Unmodified sense strand is identical to target
    sequence. Unmodified antisense strand is complementary to target sequence.
    Target SEQ
    sequence ID unmodified sense strand SEQ ID unmodified antisense strand
    Duplex start NO: 5′ to 3′ NO: 5′ to 3′
    AD-18833 1842 13029 ACUGUAACAUAGUCCGACU 13040 AGUCGGACUAUGUUACAGU
    AD-18834 1843 13030 CUGUAACAUAGUCCGACUG 13041 CAGUCGGACUAUGUUACAG
    AD-18835 1952 13031 GCCAGACACUAUAGUCGAG 13042 CUCGACUAUAGUGUCUGGC
    AD-18836 1847 13032 AACAUAGUCCGACUGCGGU 13043 ACCGCAGUCGGACUAUGUU
    AD-18837 1838 13033 GACCACUGUAACAUAGUCC 13044 GGACUAUGUUACAGUGGUC
    AD-18838 1846 13034 UAACAUAGUCCGACUGCGG 13045 CCGCAGUCGGACUAUGUUA
    AD-18839 1849 13035 CAUAGUCCGACUGCGGUAU 13046 AUACCGCAGUCGGACUAUG
    AD-18841 1957 13036 ACACUAUAGUCGAGCCAAG 13047 CUUGGCUCGACUAUAGUGU
    AD-18842 2169 13037 CAUAUAUCUGUUCUCGGUA 13048 UACCGAGAACAGAUAUAUG
    AD-18843 1788 13038 UACAGGACAAGCGAUUUAA 13049 UUAAAUCGCUUGUCCUGUA
    AD-18844 1862 13039 ACUGUAACAUAGUCCGACU 13050 UCGAGUAGAAGAAAUACCG
    Target SEQ
    sequence ID modified sense strand SEQ modified antisense strand
    Duplex start NO: 5′ to 3′ ID NO: 5′ to 3′
    AD-18833-b1 1842 13051 AcuGuAAcAuAGuccGAcudTsdT 13062 AGUCGGACuAUGUuAcAGUdTsdT
    AD-18834-b1 1843 13052 cuGuAAcAuAGuccGAcuGdTsdT 13063 cAGUCGGACuAUGUuAcAGdTsdT
    AD-18835-b1 1952 13053 GccAGAcAcuAuAGucGAGdTsdT 13064 CUCGACuAuAGUGUCUGGCdTsdT
    AD-18836-b1 1847 13054 AAcAuAGuccGAcuGcGGudTsdT 13065 ACCGcAGUCGGACuAUGUUdTsdT
    AD-18837-b1 1838 13055 GAccAcuGuAAcAuAGuccdTsdT 13066 GGACuAUGUuAcAGUGGUCdTsdT
    AD-18838-b1 1846 13056 uAAcAuAGuccGAcuGcGGdTsdT 13067 CCGcAGUCGGACuAUGUuAdTsdT
    AD-18839-b1 1849 13057 cAuAGuccGAcuGcGGuAudTsdT 13068 AuACCGcAGUCGGACuAUGdTsdT
    AD-18841-b1 1957 13058 AcAcuAuAGucGAGccAAGdTsdT 13069 CUUGGCUCGACuAuAGUGUdTsdT
    AD-18842-b1 2169 13059 cAuAuAucuGuucucGGuAdTsdT 13070 uACCGAGAAcAGAuAuAUGdTsdT
    AD-18843-b1 1788 13060 uAcAGGAcAAGcGAuuuAAdTsdT 13071 UuAAAUCGCUUGUCCUGuAdTsdT
    AD-18844-b1 1862 13061 cGGuAuuucuucuAcucGAdTsdT 13072 UCGAGuAGAAGAAAuACCGdTsdT
  • TABLE 6
    Sequences of duplexes targeting Human GSK3-alpha
    Target sequence start identifies first nucleotide in target sequence in human
    GSK3-alpha mRNA NM_002093. Unmodified sense strand is identical to target
    sequence. Unmodified antisense strand is complementary to target sequence.
    Target
    sequence SEQ ID unmodified sense strand SEQ ID unmodified antisense strand
    Duplex start NO: 5′ to 3′ NO: 5′ to 3′
    huGSKA-1 1273 13073 AGCUCCAGAUCAUGAGAAA 13081 UUUCUCAUGAUCUGGAGCU
    huGSKA-2 1979 13074 UCUGCUGGAGUAUACACCA 13082 UGGUGUAUACUCCAGCAGA
    huGSKA-3 1981 13075 UGCUGGAGUAUACACCAAC 13083 GUUGGUGUAUACUCCAGCA
    huGSKA-4 1676 13076 CACUGAUUAUACCUCUAGU 13084 ACUAGAGGUAUAAUCAGUG
    huGSKA-5 1839 13077 CCAAACUACACAGAAUUUA 13085 UAAAUUCUGUGUAGUUUGG
    huGSKA-6 1834 13078 UGAACCCAAACUACACAGA 13086 UCUGUGUAGUUUGGGUUCA
    huGSKA-7 1837 13079 ACCCAAACUACACAGAAUU 13087 AAUUCUGUGUAGUUUGGGU
    huGSKA-8 1838 13080 CCCAAACUACACAGAAUUU 13088 AAAUUCUGUGUAGUUUGGG
    Human GSK alpha duplexes correspond to the mouse GSK alpha duplexes as follows:
    Mouse duplex Human duplex
    AD-18821 huGSKA-1
    AD-18825 huGSKA-2
    AD-18826 huGSKA-3
    AD-18827 huGSKA-4
    AD-18828 huGSKA-5
    AD-18830 huGSKA-6
    AD-18831 huGSKA-7
    AD-18832 huGSKA-8
  • TABLE 7
    Sequences of duplexes targeting Human GSK3-beta
    Target sequence start identifies first nucleotide in target sequence in human
    GSK3-beta mRNA NM_019884. Unmodified sense strand is identical to target
    sequence. Unmodified antisense strand is complementary to target sequence.
    Target
    sequence SEQ unmodified sense strand SEQ unmodified antisense strand
    Duplex start ID NO: 5′ to 3′ ID NO: 5′ to 3′
    huGSKB-1 625 13088 ACUGCAAUAUUGUGAGGCU 13099 AGCCUCACAAUAUUGCAGU
    huGSKB-2 626 13089 CUGCAAUAUUGUGAGGCUG 13100 CAGCCUCACAAUAUUGCAG
    huGSKB-3 735 13090 GCCCGCCACUUCACCAAGG 13101 CCUUGGUGAAGUGGCGGGC
    huGSKB-4 630 13091 AAUAUUGUGAGGCUGAGAU 13102 AUCUCAGCCUCACAAUAUU
    huGSKB-5 621 13092 GACCACUGCAAUAUUGUGA 13103 UCACAAUAUUGCAGUGGUC
    huGSKB-6 629 13093 CAAUAUUGUGAGGCUGAGA 13104 UCUCAGCCUCACAAUAUUG
    huGSKB-7 632 13094 UAUUGUGAGGCUGAGAUAC 13105 GUAUCUCAGCCUCACAAUA
    huGSKB-8 740 13095 CCACUUCACCAAGGCCAAG 13106 CUUGGCCUUGGUGAAGUGG
    huGSKB-9 952 13096 CCUACAUCUGUUCUCGCUA 13107 UAGCGAGAACAGAUGUAGG
    huGSKB-10 571 13097 UCCAGGACAAGAGGUUCAA 13108 UUGAACCUCUUGUCCUGGA
    huGSKB-11 645 13098 AGAUACUUUUUCUACUCCA 13109 UGGAGUAGAAAAAGUAUCU
    Human GSK beta duplexes correspond to the mouse GSK beta duplexes as follows:
    Mouse Duplex Human Duplex
    AD-18833 huGSKB-1
    AD-18834 huGSKB-2
    AD-18835 huGSKB-3
    AD-18836 huGSKB-4
    AD-18837 huGSKB-5
    AD-18838 huGSKB-6
    AD-18839 huGSKB-7
    AD-18841 huGSKB-8
    AD-18842 huGSKB-9
    AD-18843 huGSKB-10
    AD-18844 huGSKB-11

Claims (32)

1. A double-stranded ribonucleic acid (dsRNA), comprising a sense strand and an antisense strand, the sense strand comprising a first sequence and the antisense strand comprising a second sequence, the second sequence comprising a region complementary to an mRNA encoding a GSK-3, and wherein said region of complementarity is less than 30 nucleotides in length.
2. (canceled)
3. The dsRNA of claim 1, the second sequence comprising a region complementary to at least 15 nucleotides of the sense strand of huGSKA-3 (SEQ ID NO:13075).
4. The dsRNA of claim 1, the second sequence comprising a region complementary to the sense strand of huGSKA-3 (SEQ ID NO:13075).
5. The dsRNA of claim 1, the antisense strand comprising at least 15 nucleotides of the antisense strand of huGSKA-3 (SEQ ID NO:13083).
6. The dsRNA of claim 1, the antisense strand comprising the antisense strand of huGSKA-3 (SEQ ID NO:13083).
7. The dsRNA of claim 1, the antisense strand consisting of the antisense strand of huGSKA-3 (SEQ ID NO:13083).
8. The dsRNA of claim 1, the sense strand comprising at least 15 nucleotides of the sense strand of huGSKA-3 (SEQ ID NO:13075).
9. The dsRNA of claim 1, the sense strand comprising the sense strand of huGSKA-3 (SEQ ID NO:13075).
10. The dsRNA of claim 1, the sense strand consisting of the sense strand of huGSKA-3 (SEQ ID NO:13075).
11. The dsRNA of claim 1, the sense strand consisting of the sense strand of huGSKA-3 (SEQ ID NO:13075) and the antisense strand consisting of the antisense strand of huGSKA-3 (SEQ ID NO:13083).
12. (canceled)
13. (canceled)
14. (canceled)
15. (canceled)
16. The dsRNA of claim 1, wherein said dsRNA comprises at least one modified nucleotide.
17. The dsRNA of claim 16, wherein at least one of said modified nucleotides is chosen from the group of: a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.
18. The dsRNA of claim 16, wherein said modified nucleotide is chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.
19. The dsRNA of claim 16, comprising at least one 2′-O-methyl modified nucleotide and at least one nucleotide comprising a 5′-phosphorothioate group,
20. The dsRNA of claim 1, wherein the region of complementary is at least 15 nucleotides in length.
21. The dsRNA of claim 1, wherein the region of complementarity is between 19 and 21 nucleotides in length.
22. The dsRNA of claim 1, wherein the region of complementarity is 19 nucleotides in length.
23. The dsRNA of claim 1, wherein administration of the dsRNA inhibits expression of GSK3 by more than 40%.
24. The dsRNA of claim 1, wherein the dsRNA exhibits an 1050 of less than or equal to 10 nM in suppressing GSK3.
25. The dsRNA of claim 1, wherein the dsRNA exhibits an 1050 of less than or equal to 1.0 nM in suppressing GSK3.
26. A cell comprising the dsRNA of claim 1.
27. A vector comprising at least one strand of the dsRNA of claim 1.
28. A cell comprising the vector of claim 27.
29. A pharmaceutical composition for inhibiting expression of an GSK-3 gene comprising the dsRNA of claim 1.
30. A method of inhibiting GSK-3 expression in a cell, the method comprising:
(a) introducing into the cell the dsRNA of claim 1; and
(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a GSK-3 gene, thereby inhibiting expression of a GSK-3 gene in the cell.
31. A method of treating a disorder mediated by GSK-3 expression comprising administering to a human in need of such treatment a therapeutically effective amount of the dsRNA of claim 1.
32. (canceled)
US13/003,740 2008-07-11 2009-07-13 Compositions And Methods For Inhibiting Expression Of GSK-3 Genes Abandoned US20110184046A1 (en)

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