SI2287305T2 - Z rna-interferenco posredovano inhibiranje izražanja gena z uporabo male interferenčne nukleinske kisline (sina) - Google Patents
Z rna-interferenco posredovano inhibiranje izražanja gena z uporabo male interferenčne nukleinske kisline (sina) Download PDFInfo
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- SI2287305T2 SI2287305T2 SI200332420T SI200332420T SI2287305T2 SI 2287305 T2 SI2287305 T2 SI 2287305T2 SI 200332420 T SI200332420 T SI 200332420T SI 200332420 T SI200332420 T SI 200332420T SI 2287305 T2 SI2287305 T2 SI 2287305T2
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- Prior art keywords
- nucleic acid
- nucleotides
- sina
- pyrimidine nucleotides
- acid molecule
- Prior art date
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- 150000007523 nucleic acids Chemical class 0.000 title claims abstract 23
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- 230000014509 gene expression Effects 0.000 title claims abstract 5
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- 230000005764 inhibitory process Effects 0.000 title claims 2
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- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract 6
- 239000002719 pyrimidine nucleotide Substances 0.000 claims 13
- 150000003230 pyrimidines Chemical class 0.000 claims 13
- 239000012634 fragment Substances 0.000 claims 11
- 230000000692 anti-sense effect Effects 0.000 claims 10
- 239000002773 nucleotide Substances 0.000 claims 9
- 125000003729 nucleotide group Chemical group 0.000 claims 9
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- 108091028043 Nucleic acid sequence Proteins 0.000 claims 3
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Claims (24)
- Z RNA-interferenco posredovano inhibiranje izražanja gena z uporabo male interferenčne nukleinske kisline (siNA) Patentni zahtevki1. Kemijsko spremenjena molekula sintetične male interferenčne nukleinske kisline (siNA), ki je sposobna znižati nivo izražanja tarčnega gena v celicah z RNA-interferenco (RNAi), pri čemer siNA obsega: (a) smiselno verigo in protismiselno verigo; (b) vsaka veriga molekule nukleinske kisline je neodvisno dolga od 18 do 24 nukleotidov in siNA dupleks obsega od 17 do 23 baznih parov; (c) 5, 6, 7, 8, 9, 10 ali več pirimidinskih nukleotidov smiselne verige in/ali 5, 6, 7, 8, 9, 10 ali več pirimidinskih nukleotidov protismiselne verige je kemijsko spremenjenih z nukleotidi 2’-deoksi, 2’-0-metil in/ali 2’-deoksi-2’-fluoro; in (d) ena ali več fosforotioatnih internukleotidnih vezi in molekula terminalna kape (ang. cap molecule) na 3’-koncu, 5’-koncu ali na 3’-koncu in 5’-koncu je prisotnih v isti ali različni verigi od siNA pri čemer molekula siNA obsega dva ločena oligonukleotidna fragmenta, pri čemer en fragment obsega smiselno regijo in drugi fragment obsega protismiselno regijo, in pri čemer fragment, ki obsega smiselno regijo, vključuje del terminalne kape na 5’-koncu, 3’-koncu ali tako na 5’-koncu kot tudi na 3’-koncu.
- 2. Molekula siNA po zahtevku 1, pri čemer so purinski nukleotidi v smiselni regiji 2’-deoksi purinski nukleotidi in pri čemer so pirimidinski nukleotidi v smiselni regiji 2’-deoksi-2’-fluoro pirimidinski nukleotidi.
- 3. Molekula siNA po zahtevku 1, pri čemer so pirimidinski nukleotidi v protismiselni regiji 2’-deoksi-2’-fluoro pirimidinski nukleotidi in pri čemer so purinski nukleotidi v protismiselni regiji 2’-0-metil purinski nukleotidi.
- 4. Molekula siNA po zahtevku 1, pri čemer so purinski nukleotidi, ki so prisotni v protismiselni regiji, 2’-deoksi purinski nukleotidi, in pri čemer so pirimidinski nukleotidi, ki so prisotni v protismiselni regiji, 2’-deoksi-2’-fluoro pirimidinski nukleotidi.
- 5. Molekula siNA po katerem koli od zahtevkov 1, 3 in 4, pri čemer protismiselna regija obsega fosforotioatno internukleotidno vez pri 3’-koncu protismiselne regije.
- 6. Molekula siNA po zahtevku 1, pri čemer vsak od dveh fragmentov molekule siNA obsega 21 nukleotidov.
- 7. Molekula siNA po zahtevku 1, pri čemer 19 nukleotidov vsakega fragmenta molekule siNA tvori bazne pare s komplementarnimi nukleotidi drugega fragmenta molekule siNA in pri čemer dva 3’-terminalna nukleotida vsakega fragmenta molekule siNA ne tvorita baznih parov z nukleotidi drugega fragmenta molekule siNA.
- 8. Molekula siNA po zahtevku 1, pri čemer 21 nukleotidov protismiselne regije tvori bazne pare z nukleotidnim zaporedjem RNA, ki kodira tarčni gen ali njegov del.
- 9. Molekula siNA po zahtevku 1, pri čemer so purinski nukleotidi v smiselni regiji purinski ribonukleotidi in pri čemer so pirimidinski nukleotidi v smiselni regiji 2’-deoksi-2’-fluoro pirimidinski nukleotidi in pri čemer smiselni fragment vključuje del terminalne kape pri 5’-koncu in 3’-koncu.
- 10. Molekula siNA po zahtevku 1, pri čemer so purinski nukleotidi v smiselni regiji purinski ribonukleotidi in pri čemer so pirimidinski nukleotidi v smiselni regiji 2’-0-metil pirimidinski nukleotidi in pri čemer smiselni fragment vključuje del terminalne kape pri 5’-koncu in 3’-koncu.
- 11. Molekula nukleinske kisline po zahtevku 1, pri čemer 2’-deoksi pirimidinski nukleotidi predstavljajo 5, 6, 7, 8, 9, 10 ali več pirimidinskih nukleotidov v smiselni verigi.
- 12. Molekula nukleinske kisline po zahtevku 1, pri čemer 2’-0-metil pirimidinski nukleotidi predstavljajo 5, 6, 7, 8, 9, 10 ali več pirimidinskih nukleotidov v smiselni verigi.
- 13. Molekula nukleinske kisline po zahtevku 1, pri čemer 2’-deoksi-2’-fluoro pirimidinski nukleotidi predstavljajo 5, 6, 7, 8, 9, 10 ali več pirimidinskih nukleotidov v smiselni verigi.
- 14. Molekula nukleinske kisline po zahtevku 1, pri čemer 2’-0-metil pirimidinski nukleotidi predstavljajo 5, 6, 7, 8, 9, 10 ali več pirimidinskih nukleotidov v smiselni verigi.
- 15. Molekula nukleinske kisline po zahtevku 1, pri čemer 2’-deoksi-2’-fluoro pirimidinski nukleotidi predstavljajo 5, 6, 7, 8, 9,10 ali več pirimidinskih nukleotidov v smiselni verigi.
- 16. Molekula nukleinske kisline po katerem koli od predhodnih zahtevkov, pri čemer je del terminalne kape invertiran deoksi abazični del.
- 17. Molekula nukleinske kisline po katerem koli od predhodnih zahtevkov, ki obsega 1, 2, 3, 4, 5, 6, 7, 8, 9 ali 10 fosforotioatnih internukleotidnih vezi.
- 18. Molekula nukleinske kisline po katerem koli od predhodnih zahtevkov, pri čemer molekula nukleinske kisline obsega ribonukleotide.
- 19. Molekula nukleinske kisline po katerem koli od predhodnih zahtevkov, pri čemer je tarčna RNA zaporedje sesalske RNA.
- 20. Molekula nukleinske kisline po katerem koli od predhodnih zahtevkov, pri čemer je tarčna RNA zaporedje človeške RNA.
- 21. Molekula nukleinske kisline po zahtevku 20, pri čemer zaporedje človeške RNA obsega zaporedje človeškega VEGFr-1, VEGFr-2, HER1, HER2, HER3, HER4, TERT, telomerazne RNA, NFkappaB, Re1-A, NOGO, NOGOr, RAS, RAF, CD20, METAP2, CLCA1, fosfolambana ali PTP1B.
- 22. Molekula nukleinske kisline po katerem koli od zahtevkov od 1 do 18, pri čemer je tarčna RNA zaporedje virusne RNA.
- 23. Molekula nukleinske kisline po zahtevku 22, pri čemer zaporedje virusne RNA obsega zaporedje HBV, HCV, HIV-1, HIV-2, WNV, CMV, RSV, virusa influenze, rinovirusa, papilomavirusa, HSV ali HTLV.
- 24. Sestavek, ki obsega molekulo nukleinske kisline po katerem koli od predhodnih zahtevkov, in farmacevtsko sprejemljiv nosilec ali razredčilo.
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EP10008929.1A EP2287305B2 (en) | 2002-02-20 | 2003-02-20 | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
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DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
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US7423142B2 (en) | 2001-01-09 | 2008-09-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
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US20050148530A1 (en) | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US20050171040A1 (en) * | 2001-05-18 | 2005-08-04 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of cholesteryl ester transfer protein (CEPT) gene expression using short interfering nucleic acid (siNA) |
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US7517864B2 (en) | 2001-05-18 | 2009-04-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
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DE10163098B4 (de) | 2001-10-12 | 2005-06-02 | Alnylam Europe Ag | Verfahren zur Hemmung der Replikation von Viren |
DE10202419A1 (de) | 2002-01-22 | 2003-08-07 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens |
US9657294B2 (en) | 2002-02-20 | 2017-05-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
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GB0212303D0 (en) * | 2002-05-28 | 2002-07-10 | Isis Innovation | Molecular targetting of IGF-1 receptor |
GB0212302D0 (en) * | 2002-05-28 | 2002-07-10 | Isis Innovation | Method of selecting targets for gene silencing by RNA interference |
SI2258847T1 (sl) | 2002-08-05 | 2017-08-31 | Silence Therapeutics Gmbh | Nadaljnje nove oblike molekul interferenčne RNA |
WO2004014933A1 (en) | 2002-08-07 | 2004-02-19 | University Of Massachusetts | Compositions for rna interference and methods of use thereof |
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