KR960706358A - 아이코사노이드 형성을 억제하는 안티센스 올리고뉴클레오타이드(Antisense Oligonucleotides to Suppress Elcosanoid Formation) - Google Patents
아이코사노이드 형성을 억제하는 안티센스 올리고뉴클레오타이드(Antisense Oligonucleotides to Suppress Elcosanoid Formation)Info
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- KR960706358A KR960706358A KR1019960703267A KR19960703267A KR960706358A KR 960706358 A KR960706358 A KR 960706358A KR 1019960703267 A KR1019960703267 A KR 1019960703267A KR 19960703267 A KR19960703267 A KR 19960703267A KR 960706358 A KR960706358 A KR 960706358A
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- Prior art keywords
- oligonucleotide
- cyclooxygenase
- antisense
- antisense oligonucleotide
- deoxynucleotide sequence
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Links
- 239000000074 antisense oligonucleotide Substances 0.000 title claims abstract description 27
- 238000012230 antisense oligonucleotides Methods 0.000 title claims abstract description 27
- 108020000948 Antisense Oligonucleotides Proteins 0.000 title description 2
- 230000015572 biosynthetic process Effects 0.000 title 2
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 44
- 230000000692 anti-sense effect Effects 0.000 claims abstract description 9
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims abstract 11
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims abstract 11
- 108020004999 messenger RNA Proteins 0.000 claims abstract 5
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 238000000034 method Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 3
- 230000002028 premature Effects 0.000 abstract 3
- 150000003180 prostaglandins Chemical class 0.000 abstract 2
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 abstract 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 abstract 1
- 206010018364 Glomerulonephritis Diseases 0.000 abstract 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 abstract 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 abstract 1
- 210000001691 amnion Anatomy 0.000 abstract 1
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- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
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- 230000002526 effect on cardiovascular system Effects 0.000 abstract 1
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- 229910017604 nitric acid Inorganic materials 0.000 abstract 1
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- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 abstract 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
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Abstract
본 발명은 조기분말, 양수막의 조기파열, 조기확장, 자간전증, 자궁내막증식증, 류미티스성 관절염, ARDS 및 사구체신염을 치료할 수 있는 신규한 안티센스 울리고뉴클레오타이드를 제공한다. 이 약물은 사이클로옥시게나제의 암호화 mRNA 또는 트롬복산 A2신타제 단백질의 암호화 mRNA의 발현을 중지시키는 안티센스 올리고뉴클레오타이드이다. 일단 사이클로옥시게나제의 암호화 mRNA가 억제되면, 사이클로옥시게나제의 생성이 억제되고 이에따라 프로스타글란딘 및 트롬복산과 같은 사이클로옥시게나제 산물의 생성이 억제된다. 따라서, 이 안티센스 올리고뉴클레오타이드는 사이클로옥시게나제 산물인 프로스타글란딘 및 트롬복산 대사와 관련된 질산의 새로운 치료법을 제공한다. 이와 같은 질환으로는 사이클로옥시게나제 산물이 질병의 발생 및 발전에 영향을 주는 면역학적, 재생적, 심장혈관, 피부학적, 중추신경계 질병이 포함된다. 본 발명의 두 번째 목적은 사이클로옥시게나제 산물과 연관된 질병의 연구를 위한 새로운 시약을 제공하는데 있다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 PMA로 처리된(레인 2); 5μM 안티센스 S-올리고뉴클레오타이드 mCOX-2.2로 예비배양되고 PMA로 처리된(레인 4); 5μM 안티센스 S-올리고뉴클레오타이드 mCOX-2.2로 예비배양되고 PMA로 처리되지 않은(레인 3); 10μM 안티센스 S-올리고뉴클레오타이드 mCOX-2.2로 예비배양되고 PMA로 처리된 (레인 6); 10μM 안티센스 S-올리고뉴클레오타이드 mCOX-2.2로 예비배양되고 PMA로 처리되지 않은 (레인 5); 및 PMA 또는 S-올리고뉴클레오타이드로 처리되지 않은 (레인 1)마우스 3T3 세포에서 RNA 발현의 COX-2를 보여주는 노던 블롯이다. 제2도는 용량 의존적 방식에 따른 PGE2생성의 mCOX-2.4 안티센스 올리고뉴클레오타이드 억제를 증명하는 그래프이다, 세포를 mCOX-2.4 서열에 상응하는 S-올리고뉴클레오타이드 S 또는 10μM과 함께 18시간 예방배양하였다. PMA로 도전된 세포는 빗금친 막대로 나타나 있다. PMA로 도전되지 않은 세포는 빗금이 없는 막대로 나타나 있다. 데이터는 4회 중복의 평균 표준오차 값이다. 제3도는 PMA 자극된 3T3 세포에서 PGE2생성의 mCOX-2.2, mCOX-2.3, 및 mCOX-2.4 안티센스 S-올리고뉴클레오타이드 억제를 증명하는 그래프이다. PMA로 도전된 세포는 검정색 막대 및 빗금친 막대로 나타나 있다. PMA로 도전되지 않은 세포는 빗금이 없는 막대로 나타나 있다. 이 데이터는 8회 중복의 평균 표준편차 값이다. 제4도는 자극된 마우스 3T3 세포에서 PGE2생성을 약화하는 mCOX-2.4 안티센스 올리고뉴클레오타이드를 증명하는 그래프이다. 세포를 mCOX-2.4 서열에 상응하는 N-올리고뉴클레오타이드는 또는 S-올리고뉴클레오타이드 10μM과 함께 18시간 예비 배양하였다. PMA로 도전된 세포는 빗금친 막대로 나타나 있다. PMA로 도전되지 않은 세포는 빗금이 없는 맥대를 나타나 있다. 본 데이터는 4회 중복의 평균 표준편차 값이다, 제5도는 PMA 자극된 WISH 세포에서 PGE2생성의 hCOX-2.1, hCOX-2.2, hCOX-2.8, 및 hCOX-2.9 안티센스 S-올리고뉴클레오타이드 억제를 증명하는 그래프이다. PMA로 도전되지 않은 세포는 빗금이 없는 막대로 나타나 있다. 데이터는 4 내지 8회 중복의 평균 ±표준편차 값이다.
Claims (22)
- 사이클로옥시게나제의 암호화 mRNA와 결합하고 사이클로옥시게나제의 생성을 억제하는 안티센스 올리고뉴클레오타이드.
- 제1항에 있어서, 안티센스 올리고뉴클레오타이드가 하기의 데옥시뉴클레오타이드 서열로 이루어진 그룹중에서 선택되는 안티센스 올리고뉴클레오타이드 : 5′-GGGAGTGGATGGATGTGC-3′; 5′-AAAACTCCTCCCTCCAGA-3′; 5′-CCACGAAAACCCACATCA-3′; 5′-CCGAAAGTGGCAAAATCA-3′; 5′-TCTGGGAGTGGATGGATG-3′; 5′-AGAGGTGGCAGCGGAGGT-3′; 5′-AGAGGAATCAATGCTGAT-3′; 5′- GAGCATCGCAGAGGTGGC-3′; 5′- TTGGACCCCTTTGTTTGA-3′; 5′- GACTCCGGCTCATGGCGC-3′; 5′- GTAGGCTTTGCTGTCTGA-3; 5′-CGGGCGAGCATC-3′; 5′- GCAGCGGCGGGCAGGGCG-3′; 5′-GAGCATCGCAGCGGCG-3′; 5′-GGCGAGCATCGCAGCGGC-3′; 5′-GCGCGGGCGAGCATC-3′; 5′-AGGGCGCGGGCGAGCATC-3′; 5′-ATGACTCCTTTCTCCGCA-3′; 및 5′-TTTTGGCGGGGTTATGGGGT-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GGGAGTGGATGGATGTGC-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-AAAACTCCTCCCTCCAGA-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-CCACGAAAACCCACATCA-3′
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-CCGAAAGTGGCAAAATCA-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-TCTGGGAGTGGATGGATG-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-AGAGGTGGCAGCGGAGGT-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-TTGGACCCCTTTGTTTGA-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GAGCATCGCAGAGGTGGC-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-TTGGACCCCTTTGTTTGA-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GACTCCGGCTCATGGCGC-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GTAGGCTTTGCTGTCTGA-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-CGGGCGAGCATC-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GCAGCGGCGGGCAGGGCG-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GAGCATCGCAGCGGCG-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GGCGAGCATCGCAGCGGC-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-GCGCGGGCGAGCATC-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-AGGGCGCGGGCGAGCATC-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-ATGACTCCTTTCTCCGCA-3′.
- 제2항에 있어서, 올리고뉴클레오타이드가 다음의 데옥시뉴클레오타이드 서열을 갖는 안티센스 올리고뉴클레오타이드 : 5′-TTTTGGCGGGGTTATGGGGT-3′.
- 사이클로옥시게나제의 암호화 mRNA와 결합하는 하나 이상의 안티센스 뉴클레오타이드를 제공하고, 이 안티센스 뉴클레오타이드를 동물에 투여하여, 그 동물에서의 사이클로옥시게나제 산물의 생성을 감소시키는 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17008993A | 1993-12-17 | 1993-12-17 | |
| US08/170,089 | 1993-12-17 | ||
| PCT/US1994/014508 WO1995016466A1 (en) | 1993-12-17 | 1994-12-16 | Antisense oligonucleotides to suppress eicosanoid formation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR960706358A true KR960706358A (ko) | 1996-12-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019960703267A Withdrawn KR960706358A (ko) | 1993-12-17 | 1994-12-16 | 아이코사노이드 형성을 억제하는 안티센스 올리고뉴클레오타이드(Antisense Oligonucleotides to Suppress Elcosanoid Formation) |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US5859229A (ko) |
| EP (1) | EP0796109A1 (ko) |
| JP (1) | JPH09510954A (ko) |
| KR (1) | KR960706358A (ko) |
| AU (1) | AU687508B2 (ko) |
| CA (1) | CA2179168A1 (ko) |
| WO (1) | WO1995016466A1 (ko) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19824230A1 (de) * | 1998-05-29 | 1999-12-02 | Starzinski Powitz Anna | Neues Endometriose-assoziiertes Gen |
| US6344323B1 (en) * | 1998-09-16 | 2002-02-05 | Vitagenix, Inc. | Compositions and methods for inhibiting cox-2 expression and treating cox-2 associated disorders by using cox-2 antisense oligonucleotides |
| JP2012502991A (ja) | 2008-09-22 | 2012-02-02 | アールエックスアイ ファーマシューティカルズ コーポレーション | 皮膚適用におけるｒｎａ干渉 |
| EP3560503B1 (en) * | 2010-03-24 | 2021-11-17 | Phio Pharmaceuticals Corp. | Rna interference in dermal and fibrotic indications |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5112868A (en) * | 1988-05-19 | 1992-05-12 | Warner-Lambert Company | Hydroxamate derivatives of selected nonsteroidal antiinflammatory acyl residues having cyclooxygenase and 5-lipoxygenase inhibition |
| WO1991016901A1 (en) * | 1990-04-30 | 1991-11-14 | Isis Pharmaceuticals, Inc. | Oligonucleotide modulation of arachidonic acid metabolism |
| GB9021571D0 (en) * | 1990-10-04 | 1990-11-21 | Ici Plc | Heterocyclic acids |
| US5543297A (en) * | 1992-12-22 | 1996-08-06 | Merck Frosst Canada, Inc. | Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity |
-
1994
- 1994-12-16 KR KR1019960703267A patent/KR960706358A/ko not_active Withdrawn
- 1994-12-16 WO PCT/US1994/014508 patent/WO1995016466A1/en not_active Ceased
- 1994-12-16 EP EP95907219A patent/EP0796109A1/en not_active Withdrawn
- 1994-12-16 AU AU15522/95A patent/AU687508B2/en not_active Ceased
- 1994-12-16 CA CA002179168A patent/CA2179168A1/en not_active Abandoned
- 1994-12-16 JP JP7516967A patent/JPH09510954A/ja active Pending
-
1996
- 1996-04-03 US US08/627,254 patent/US5859229A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US5859229A (en) | 1999-01-12 |
| AU687508B2 (en) | 1998-02-26 |
| CA2179168A1 (en) | 1995-06-22 |
| EP0796109A1 (en) | 1997-09-24 |
| AU1552295A (en) | 1995-07-03 |
| WO1995016466A1 (en) | 1995-06-22 |
| JPH09510954A (ja) | 1997-11-04 |
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