RU2013156865A - Композиции и способы ингибирования экспрессии генов аполипопротеина с-iii (арос3) - Google Patents
Композиции и способы ингибирования экспрессии генов аполипопротеина с-iii (арос3) Download PDFInfo
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- 230000002401 inhibitory effect Effects 0.000 title claims abstract 7
- 239000000203 mixture Substances 0.000 title claims 3
- 102000030169 Apolipoprotein C-III Human genes 0.000 title 1
- 108010056301 Apolipoprotein C-III Proteins 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 title 1
- 125000003729 nucleotide group Chemical group 0.000 claims abstract 37
- 239000002773 nucleotide Substances 0.000 claims abstract 22
- 230000000692 anti-sense effect Effects 0.000 claims abstract 10
- 101150001527 APOC3 gene Proteins 0.000 claims abstract 7
- 108091081021 Sense strand Proteins 0.000 claims abstract 7
- 229920002477 rna polymer Polymers 0.000 claims abstract 4
- 150000001841 cholesterols Chemical class 0.000 claims abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 102100030970 Apolipoprotein C-III Human genes 0.000 claims 4
- 101000793223 Homo sapiens Apolipoprotein C-III Proteins 0.000 claims 4
- 239000003446 ligand Substances 0.000 claims 2
- 150000002632 lipids Chemical class 0.000 claims 2
- 206010014486 Elevated triglycerides Diseases 0.000 claims 1
- 102000004882 Lipase Human genes 0.000 claims 1
- 108090001060 Lipase Proteins 0.000 claims 1
- 239000004367 Lipase Substances 0.000 claims 1
- 108010013563 Lipoprotein Lipase Proteins 0.000 claims 1
- 102100022119 Lipoprotein lipase Human genes 0.000 claims 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical group CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 235000019421 lipase Nutrition 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 108020004999 messenger RNA Proteins 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 abstract 2
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 abstract 1
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Abstract
1. Двухцепочечная рибонуклеиновая кислота (дцРНК) для ингибирования экспрессии гена APOC3, где указанная дцРНК содержит смысловую цепь и антисмысловую цепь, каждая из 30 нуклеотидов или менее в длину, где указанная антисмысловая цепь содержит, по меньшей мере, 15 смежных нуклеотидов антисмысловой последовательности в таблице 1, 2, 6, 7 или 10.2. Двухцепочечная рибонуклеиновая кислота (дцРНК) для ингибирования экспрессии гена APOC3, где указанная дцРНК содержит смысловую цепь, состоящую из нуклеотидной последовательности SEQ ID NO:70, и антисмысловую цепь, состоящую из нуклеотидной последовательности SEQ ID NO:151 (AD-45149.1UM).3. дцРНК по п. 1, где последовательность смысловой цепи выбрана из таблицы 1, 2, 6, 7 или 10, и последовательность антисмысловой цепи выбрана из таблицы 1, 2, 6, 7 или 10.4. дцРНК по п. 1 или 2, где, по меньшей мере, один нуклеотид дцРНК представляет собой модифицированный нуклеотид.5. дцРНК по п. 4, где указанный модифицированный нуклеотид выбран из группы, состоящей из: 2′-О-метил-модифицированного нуклеотида, нуклеотида, содержащего 5′-фосфоротиоатную группу, и концевого нуклеотида, соединенного с холестериновым производным или бисдециламидной группой додекановой кислоты.6. дцРНК по п. 4, где указанный модифицированный нуклеотид выбран из группы, состоящей из: 2′-дезокси-2′-фтор-модифицированного нуклеотида, 2′-дезокси-модифицированного нуклеотида, замкнутого нуклеотида, нуклеотида, не содержащего основания, 2′-амино-модифицированного нуклеотида, 2′-алкил-модифицированного нуклеотида, морфолинонуклеотида, фосфороамидата и нуклеотида, содержащего неприродное основание.7. дцРНК по п. 1, где, по меньшей мере, одна цепь содержит 3′-
Claims (24)
1. Двухцепочечная рибонуклеиновая кислота (дцРНК) для ингибирования экспрессии гена APOC3, где указанная дцРНК содержит смысловую цепь и антисмысловую цепь, каждая из 30 нуклеотидов или менее в длину, где указанная антисмысловая цепь содержит, по меньшей мере, 15 смежных нуклеотидов антисмысловой последовательности в таблице 1, 2, 6, 7 или 10.
2. Двухцепочечная рибонуклеиновая кислота (дцРНК) для ингибирования экспрессии гена APOC3, где указанная дцРНК содержит смысловую цепь, состоящую из нуклеотидной последовательности SEQ ID NO:70, и антисмысловую цепь, состоящую из нуклеотидной последовательности SEQ ID NO:151 (AD-45149.1UM).
3. дцРНК по п. 1, где последовательность смысловой цепи выбрана из таблицы 1, 2, 6, 7 или 10, и последовательность антисмысловой цепи выбрана из таблицы 1, 2, 6, 7 или 10.
4. дцРНК по п. 1 или 2, где, по меньшей мере, один нуклеотид дцРНК представляет собой модифицированный нуклеотид.
5. дцРНК по п. 4, где указанный модифицированный нуклеотид выбран из группы, состоящей из: 2′-О-метил-модифицированного нуклеотида, нуклеотида, содержащего 5′-фосфоротиоатную группу, и концевого нуклеотида, соединенного с холестериновым производным или бисдециламидной группой додекановой кислоты.
6. дцРНК по п. 4, где указанный модифицированный нуклеотид выбран из группы, состоящей из: 2′-дезокси-2′-фтор-модифицированного нуклеотида, 2′-дезокси-модифицированного нуклеотида, замкнутого нуклеотида, нуклеотида, не содержащего основания, 2′-амино-модифицированного нуклеотида, 2′-алкил-модифицированного нуклеотида, морфолинонуклеотида, фосфороамидата и нуклеотида, содержащего неприродное основание.
7. дцРНК по п. 1, где, по меньшей мере, одна цепь содержит 3′-неспаренный конец, по меньшей мере, из 1 нуклеотида.
8. дцРНК по п. 1, где каждая цепь содержит 3′-неспаренный конец, по меньшей мере, из 2 нуклеотидов.
9. дцРНК по п. 1 или 2, дополнительно содержащая лиганд.
10. дцРНК по п. 9, где указанный лиганд конъюгирован с 3′-концом смысловой цепи дцРНК.
11. дцРНК по п. 1 или 2, дополнительно содержащая, по меньшей мере, один N-ацетилгалактозамин.
12. Клетка, содержащая дцРНК по любому из предшествующих пунктов.
13. Вектор, кодирующий, по меньшей мере, одну цепь дцРНК по п. 1.
14. Клетка, содержащая вектор по п. 13.
15. Фармацевтическая композиция для ингибирования экспрессии гена APOC3, содержащая дцРНК по любому из пп. 1-11.
16. Фармацевтическая композиция по п. 15, содержащая липидный состав.
17. Фармацевтическая композиция по п. 15, содержащая липидный состав, содержащий МС3.
18. Способ ингибирования экспрессии APOC3 в клетке, включающий:
(a) приведение клетки в контакт с дцРНК по любому из пп. 1-11; и
(b) выдерживание клетки, полученной на стадии (а), в течение периода времени, достаточного для достижения разрушения мРНК транскрипта гена APOC3, посредством чего ингибируется экспрессия гена APOC3 в клетке.
19. Способ по п. 18, где экспрессия APOC3 ингибируется, по меньшей мере, на 30%.
20. Способ лечения нарушения, опосредованного экспрессией APOC3, включающий введение человеку, нуждающемуся в таком лечении, терапевтически эффективного количества дцРНК APOC3 по любому из пп. 1-11 или фармацевтической композиции по пп. 15, 16 или 17.
21. Способ по п. 20, где указанное нарушение представляет собой повышенные уровни триглицеридов.
22. Способ по п. 20, где указанное нарушение представляет собой уровни триглицеридов >150 мг/дл или >500 мг/дл.
23. Способ по п. 20, где введение вызывает повышение активности липопротеинлипазы и/или липазы печени.
24. Способ по п. 20, где дцРНК или фармацевтическую композицию вводят в дозе приблизительно от 0,01 мг/кг до приблизительно 10 мг/кг или приблизительно от 0,5 мг/кг до приблизительно 50 мг/кг.
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| Application Number | Priority Date | Filing Date | Title |
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| US201161499620P | 2011-06-21 | 2011-06-21 | |
| US61/499,620 | 2011-06-21 | ||
| PCT/US2012/043642 WO2012177947A2 (en) | 2011-06-21 | 2012-06-21 | Compositions and methods for inhibition of expression of apolipoprotein c-iii (apoc3) genes |
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| RU2017128946A Division RU2774448C2 (ru) | 2011-06-21 | 2012-06-21 | Композиции и способы ингибирования экспрессии генов аполипопротеина c-iii (apoc3) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP3453761A1 (en) | 2011-08-29 | 2019-03-13 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
| KR102169899B1 (ko) | 2013-02-14 | 2020-10-26 | 아이오니스 파마수티컬즈, 인코포레이티드 | 지질단백질 리파제 결핍 (lpld) 모집단에서 아포지질단백질 c-iii (apociii) 발현의 조절 |
| DK2991656T3 (da) | 2013-05-01 | 2020-03-23 | Ionis Pharmaceuticals Inc | Sammensætninger og fremgangsmåder til modulering af apolipoprotein c-iii-ekspression |
| US9909124B2 (en) | 2013-06-21 | 2018-03-06 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating apolipoprotein C-III expression for improving a diabetic profile |
| EP3564374A1 (en) | 2013-06-21 | 2019-11-06 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulation of target nucleic acids |
| US10149855B2 (en) * | 2014-02-05 | 2018-12-11 | The Trustees Of Columbia University In The City Of New York | Gamma-secretase inhibition reduce APOC3 levels and plasma triglycerides |
| EP3137476B1 (en) | 2014-04-28 | 2019-10-09 | Ionis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
| KR20200102553A (ko) | 2014-05-01 | 2020-08-31 | 아이오니스 파마수티컬즈, 인코포레이티드 | 성장 호르몬 수용체 발현을 조절하기 위한 조성물 및 방법 |
| WO2015168532A2 (en) | 2014-05-01 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating pkk expression |
| DK3137596T3 (da) * | 2014-05-01 | 2019-09-02 | Ionis Pharmaceuticals Inc | Sammensætninger og fremgangsmåder til modulation af komplement faktor b-ekspression |
| AU2015252895B2 (en) | 2014-05-01 | 2021-07-15 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
| US10570169B2 (en) | 2014-05-22 | 2020-02-25 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| EP3169784B1 (en) * | 2014-07-16 | 2020-06-10 | Arrowhead Pharmaceuticals, Inc. | Rnai compositions to treat apoc3-related diseases |
| IL316808A (en) | 2014-08-20 | 2025-01-01 | Alnylam Pharmaceuticals Inc | Modified double-stranded RNA materials and their uses |
| BR112017004056A2 (pt) | 2014-09-12 | 2017-12-05 | Biogen Ma Inc | composições e métodos para detecção da proteína smn em um indivíduo e tratamento de um indivíduo |
| JP2017535552A (ja) * | 2014-11-17 | 2017-11-30 | アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | アポリポタンパク質Ｃ３（ＡＰＯＣ３）ｉＲＮＡ組成物およびその使用方法 |
| WO2016154127A2 (en) * | 2015-03-20 | 2016-09-29 | Protiva Biotherapeutics, Inc. | Compositions and methods for treating hypertriglyceridemia |
| AU2016294347B2 (en) | 2015-07-10 | 2022-07-28 | Ionis Pharmaceuticals, Inc. | Modulators of diacyglycerol acyltransferase 2 (DGAT2) |
| RU2018113709A (ru) | 2015-09-24 | 2019-10-30 | Айонис Фармасьютикалз, Инк. | Модуляторы экспрессии kras |
| CA2999341A1 (en) | 2015-11-06 | 2017-05-11 | Ionis Pharmaceuticals, Inc. | Modulating apolipoprotein (a) expression |
| DK4119569T3 (da) | 2015-11-06 | 2024-08-12 | Ionis Pharmaceuticals Inc | Konjugerede antisense-forbindelser til anvendelse i behandling |
| US11351183B2 (en) | 2016-04-22 | 2022-06-07 | Viking Therapeutics, Inc. | Use of thyroid beta-agonists |
| CA3030099A1 (en) * | 2016-07-08 | 2018-01-11 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
| CA3030864A1 (en) | 2016-07-15 | 2018-01-18 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulation of smn2 |
| WO2018067900A1 (en) | 2016-10-06 | 2018-04-12 | Ionis Pharmaceuticals, Inc. | Method of conjugating oligomeric compounds |
| CN108239644B (zh) * | 2016-12-23 | 2021-05-28 | 苏州瑞博生物技术股份有限公司 | 一种小干扰核酸和药物组合物及其用途 |
| US11242531B2 (en) | 2017-02-03 | 2022-02-08 | City Of Hope | Compositions and methods for the treatment of hypercholesterolemia |
| JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| WO2018223056A1 (en) * | 2017-06-02 | 2018-12-06 | Wave Life Sciences Ltd. | Oligonucleotide compositions and methods of use thereof |
| CA3074303A1 (en) | 2017-09-11 | 2019-03-14 | Arrowhead Pharmaceuticals, Inc. | Rnai agents and compositions for inhibiting expression of apolipoprotein c-iii (apoc3) |
| WO2019140452A1 (en) | 2018-01-15 | 2019-07-18 | Ionis Pharmaceuticals, Inc. | Modulators of dnm2 expression |
| CA3090901A1 (en) | 2018-02-12 | 2019-08-15 | Ionis Pharmaceuticals, Inc. | Modified compounds and uses thereof |
| BR112020020957B1 (pt) | 2018-05-09 | 2022-05-10 | Ionis Pharmaceuticals, Inc | Compostos oligoméricos, população e composição farmacêutica dos mesmos e seus usos |
| TWI844541B (zh) | 2018-05-11 | 2024-06-11 | 新加坡商波濤生命科學有限公司 | 寡核苷酸組成物及其使用方法 |
| WO2020018558A1 (en) | 2018-07-17 | 2020-01-23 | Aronora, Inc. | Methods for safely reducing thrombopoietin |
| US20210292768A1 (en) | 2018-08-08 | 2021-09-23 | Arcturus Therapeutics, Inc. | Compositions and agents against nonalcoholic steatohepatitis |
| TW202542311A (zh) | 2018-09-19 | 2025-11-01 | 美商Ionis製藥公司 | Pnpla3表現之調節劑 |
| WO2020132564A1 (en) | 2018-12-21 | 2020-06-25 | Ionis Pharmaceuticals, Inc. | Modulators of hsd17b13 expression |
| JP2022543136A (ja) * | 2019-08-05 | 2022-10-07 | アローヘッド ファーマシューティカルズ インコーポレイテッド | Ａｐｏｃ３関連疾患および障害の処置のための方法 |
| CN114728017B (zh) | 2019-10-14 | 2025-10-28 | 阿斯利康(瑞典)有限公司 | Pnpla3表达的调节剂 |
| KR20220143106A (ko) | 2020-02-18 | 2022-10-24 | 알닐람 파마슈티칼스 인코포레이티드 | 아포지질단백질 C3 (APOC3) iRNA 조성물 및 이의 사용 방법 |
| IL295605A (en) | 2020-02-28 | 2022-10-01 | Ionis Pharmaceuticals Inc | Compounds and methods for modulating smn2 |
| JP2023522961A (ja) | 2020-04-21 | 2023-06-01 | フラッグシップ パイオニアリング， インコーポレイテッド | 二機能性分子およびその使用方法 |
| EP4488371A3 (en) | 2020-11-18 | 2025-04-09 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
| IL309682A (en) * | 2021-06-24 | 2024-02-01 | Sirnaomics Inc | products and preparations |
| WO2023056440A1 (en) | 2021-10-01 | 2023-04-06 | Adarx Pharmaceuticals, Inc. | Prekallikrein-modulating compositions and methods of use thereof |
| JP2024543195A (ja) | 2021-12-01 | 2024-11-19 | ディセルナ ファーマシューティカルズ インコーポレイテッド | Ａｐｏｃ３発現を調節するための組成物及び方法 |
| CN114934074A (zh) * | 2022-06-01 | 2022-08-23 | 北京大学 | 一种ApoC3基因敲除仓鼠模型的构建方法 |
| CN116814621B (zh) * | 2022-08-05 | 2025-09-09 | 厦门甘宝利生物医药有限公司 | 一种抑制apoc3基因表达的rna抑制剂及其应用 |
| CN119744305A (zh) * | 2022-08-11 | 2025-04-01 | 益杰立科(上海)生物科技有限公司 | 一种表观编辑靶点的方法及用途 |
| WO2024220930A2 (en) | 2023-04-20 | 2024-10-24 | Adarx Pharmaceuticals, Inc. | Mapt-modulating compositions and methods of use thereof |
| WO2024238396A1 (en) | 2023-05-12 | 2024-11-21 | Adarx Pharmaceuticals, Inc. | Nmda ligand conjugated compounds and uses thereof |
| CN121335980A (zh) | 2023-05-26 | 2026-01-13 | 阿达尔克斯制药有限公司 | Sod1调节组合物及其使用方法 |
| AU2024313301A1 (en) | 2023-06-20 | 2025-12-11 | Adarx Pharmaceuticals, Inc. | Lrrk2-modulating compositions and methods of use thereof |
Family Cites Families (216)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US564562A (en) | 1896-07-21 | Joseph p | ||
| US513030A (en) | 1894-01-16 | Machine for waxing or coating paper | ||
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US4522808A (en) | 1980-08-15 | 1985-06-11 | Societe Anonyme Dite: L'oreal | Anti-sunburn compositions containing 2-phenyl-indole derivatives |
| US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US4426330A (en) | 1981-07-20 | 1984-01-17 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
| US4534899A (en) | 1981-07-20 | 1985-08-13 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
| JPS5927900A (ja) | 1982-08-09 | 1984-02-14 | Wakunaga Seiyaku Kk | 固定化オリゴヌクレオチド |
| FR2540122B1 (fr) | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
| US4605735A (en) | 1983-02-14 | 1986-08-12 | Wakunaga Seiyaku Kabushiki Kaisha | Oligonucleotide derivatives |
| US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
| US4824941A (en) | 1983-03-10 | 1989-04-25 | Julian Gordon | Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems |
| US4587044A (en) | 1983-09-01 | 1986-05-06 | The Johns Hopkins University | Linkage of proteins to nucleic acids |
| US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5430136A (en) | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
| US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
| US5258506A (en) | 1984-10-16 | 1993-11-02 | Chiron Corporation | Photolabile reagents for incorporation into oligonucleotide chains |
| US4828979A (en) | 1984-11-08 | 1989-05-09 | Life Technologies, Inc. | Nucleotide analogs for nucleic acid labeling and detection |
| FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
| US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
| US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| US4762779A (en) | 1985-06-13 | 1988-08-09 | Amgen Inc. | Compositions and methods for functionalizing nucleic acids |
| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| WO1987000201A1 (en) | 1985-07-05 | 1987-01-15 | Whitehead Institute For Biomedical Research | Epithelial cells expressing foreign genetic material |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US5317098A (en) | 1986-03-17 | 1994-05-31 | Hiroaki Shizuya | Non-radioisotope tagging of fragments |
| JPS638396A (ja) | 1986-06-30 | 1988-01-14 | Wakunaga Pharmaceut Co Ltd | ポリ標識化オリゴヌクレオチド誘導体 |
| US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| EP0366685B1 (en) | 1987-06-24 | 1994-10-19 | Howard Florey Institute Of Experimental Physiology And Medicine | Nucleoside derivatives |
| JP3015383B2 (ja) | 1987-09-11 | 2000-03-06 | ホワイトヘツド・インスチチユート・フオー・バイオメデイカル・リサーチ | 形質導入した線維芽およびそれらの使用 |
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
| US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
| US5525465A (en) | 1987-10-28 | 1996-06-11 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates and methods of production and applications of the same |
| DE3738460A1 (de) | 1987-11-12 | 1989-05-24 | Max Planck Gesellschaft | Modifizierte oligonukleotide |
| JP2914692B2 (ja) | 1987-12-11 | 1999-07-05 | ホワイトヘツド・インスチチユート・フオー・バイオメデイカル・リサーチ | 内皮細胞の遺伝子修飾 |
| EP0732397A3 (en) | 1988-02-05 | 1996-10-23 | Whitehead Institute For Biomedical Research | Modified hepatocytes and uses therefor |
| US5082830A (en) | 1988-02-26 | 1992-01-21 | Enzo Biochem, Inc. | End labeled nucleotide probe |
| EP0406309A4 (en) | 1988-03-25 | 1992-08-19 | The University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
| US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| US5109124A (en) | 1988-06-01 | 1992-04-28 | Biogen, Inc. | Nucleic acid probe linked to a label having a terminal cysteine |
| US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
| US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
| US5262536A (en) | 1988-09-15 | 1993-11-16 | E. I. Du Pont De Nemours And Company | Reagents for the preparation of 5'-tagged oligonucleotides |
| DE3835553C1 (en) | 1988-10-19 | 1990-03-29 | Otto Tuchenhagen Gmbh & Co Kg, 2059 Buechen, De | Method for automatic emptying and highly selective isolation of different fluids via the head space of a vessel in which the fluids are present in layered formation and apparatus for carrying out the method and for cleaning the vessel |
| GB8824593D0 (en) | 1988-10-20 | 1988-11-23 | Royal Free Hosp School Med | Liposomes |
| US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
| US5599923A (en) | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
| US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
| US5328470A (en) | 1989-03-31 | 1994-07-12 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
| US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
| US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
| US5451463A (en) | 1989-08-28 | 1995-09-19 | Clontech Laboratories, Inc. | Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides |
| US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
| US5254469A (en) | 1989-09-12 | 1993-10-19 | Eastman Kodak Company | Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| US5356633A (en) | 1989-10-20 | 1994-10-18 | Liposome Technology, Inc. | Method of treatment of inflamed tissues |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5225212A (en) | 1989-10-20 | 1993-07-06 | Liposome Technology, Inc. | Microreservoir liposome composition and method |
| US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
| US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
| EP0942000B1 (en) | 1989-10-24 | 2004-06-23 | Isis Pharmaceuticals, Inc. | 2'-Modified oligonucleotides |
| US5292873A (en) | 1989-11-29 | 1994-03-08 | The Research Foundation Of State University Of New York | Nucleic acids labeled with naphthoquinone probe |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5486603A (en) | 1990-01-08 | 1996-01-23 | Gilead Sciences, Inc. | Oligonucleotide having enhanced binding affinity |
| US7037646B1 (en) | 1990-01-11 | 2006-05-02 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
| US6783931B1 (en) | 1990-01-11 | 2004-08-31 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
| US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
| AU7579991A (en) | 1990-02-20 | 1991-09-18 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
| US5214136A (en) | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
| US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
| US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
| US5665710A (en) | 1990-04-30 | 1997-09-09 | Georgetown University | Method of making liposomal oligodeoxynucleotide compositions |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| DK0455905T3 (da) | 1990-05-11 | 1998-12-07 | Microprobe Corp | Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider |
| US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
| US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
| US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
| US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
| US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| CA2088258C (en) | 1990-07-27 | 2004-09-14 | Phillip Dan Cook | Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression |
| US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
| US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
| US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
| DK0541722T3 (da) | 1990-08-03 | 1996-04-22 | Sterling Winthrop Inc | Forbindelser og fremgangsmåder til inhibering af genekspression |
| US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
| US5512667A (en) | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
| US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
| US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
| EP0549686A4 (en) | 1990-09-20 | 1995-01-18 | Gilead Sciences Inc | Modified internucleoside linkages |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| DE69128893T2 (de) | 1990-10-31 | 1998-09-10 | Brigham & Womens Hospital | Genetische veränderung von endothelzellen |
| ATE198598T1 (de) | 1990-11-08 | 2001-01-15 | Hybridon Inc | Verbindung von mehrfachreportergruppen auf synthetischen oligonukleotiden |
| GB9100304D0 (en) | 1991-01-08 | 1991-02-20 | Ici Plc | Compound |
| JP3220180B2 (ja) | 1991-05-23 | 2001-10-22 | 三菱化学株式会社 | 薬剤含有タンパク質結合リポソーム |
| US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
| US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
| US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
| US5371241A (en) | 1991-07-19 | 1994-12-06 | Pharmacia P-L Biochemicals Inc. | Fluorescein labelled phosphoramidites |
| US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
| ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
| US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
| US5252479A (en) | 1991-11-08 | 1993-10-12 | Research Corporation Technologies, Inc. | Safe vector for gene therapy |
| US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
| US5595726A (en) | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| DE4203923A1 (de) | 1992-02-11 | 1993-08-12 | Henkel Kgaa | Verfahren zur herstellung von polycarboxylaten auf polysaccharid-basis |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
| US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| US5272250A (en) | 1992-07-10 | 1993-12-21 | Spielvogel Bernard F | Boronated phosphoramidate compounds |
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
| JP3351476B2 (ja) | 1993-01-22 | 2002-11-25 | 三菱化学株式会社 | リン脂質誘導体及びそれを含有するリポソーム |
| US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
| US5395619A (en) | 1993-03-03 | 1995-03-07 | Liposome Technology, Inc. | Lipid-polymer conjugates and liposomes |
| GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
| CA2159631A1 (en) | 1993-03-30 | 1994-10-13 | Sanofi | Acyclic nucleoside analogs and oligonucleotide sequences containing them |
| CA2159629A1 (en) | 1993-03-31 | 1994-10-13 | Sanofi | Oligonucleotides with amide linkages replacing phosphodiester linkages |
| DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| US6294664B1 (en) | 1993-07-29 | 2001-09-25 | Isis Pharmaceuticals, Inc. | Synthesis of oligonucleotides |
| US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
| US5540935A (en) | 1993-12-06 | 1996-07-30 | Nof Corporation | Reactive vesicle and functional substance-fixed vesicle |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
| US6054299A (en) | 1994-04-29 | 2000-04-25 | Conrad; Charles A. | Stem-loop cloning vector and method |
| WO2000022114A1 (en) | 1998-10-09 | 2000-04-20 | Ingene, Inc. | PRODUCTION OF ssDNA $i(IN VIVO) |
| US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
| US5543152A (en) | 1994-06-20 | 1996-08-06 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
| US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5580731A (en) | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
| US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
| US5640562A (en) | 1995-02-27 | 1997-06-17 | Sun Microsystems, Inc. | Layering hardware support code on top of an existing operating system |
| JP4335310B2 (ja) | 1995-06-07 | 2009-09-30 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | 疎水性脂質−核酸複合中間体を通して調製される脂質−核酸粒子、及び遺伝子移送のための使用 |
| US7422902B1 (en) | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| US5756122A (en) | 1995-06-07 | 1998-05-26 | Georgetown University | Liposomally encapsulated nucleic acids having high entrapment efficiencies, method of manufacturer and use thereof for transfection of targeted cells |
| US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
| CA2227989A1 (en) | 1995-08-01 | 1997-02-13 | Karen Ophelia Hamilton | Liposomal oligonucleotide compositions |
| US5858397A (en) | 1995-10-11 | 1999-01-12 | University Of British Columbia | Liposomal formulations of mitoxantrone |
| US6576752B1 (en) | 1997-02-14 | 2003-06-10 | Isis Pharmaceuticals, Inc. | Aminooxy functionalized oligomers |
| CA2294988C (en) | 1997-07-01 | 2015-11-24 | Isis Pharmaceuticals Inc. | Compositions and methods for the delivery of oligonucleotides via the alimentary canal |
| US20020169138A1 (en) * | 1997-10-24 | 2002-11-14 | Southern Research Institute | Delivery vehicles for bioactive agents and uses thereof |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
| JP5015373B2 (ja) | 1998-04-08 | 2012-08-29 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼイション | 改良表現型を得るための方法及び手段 |
| AR020078A1 (es) | 1998-05-26 | 2002-04-10 | Syngenta Participations Ag | Metodo para alterar la expresion de un gen objetivo en una celula de planta |
| EP1096921B1 (en) | 1998-07-20 | 2003-04-16 | Protiva Biotherapeutics Inc. | Liposomal encapsulated nucleic acid-complexes |
| EP1117776A1 (en) | 1998-10-09 | 2001-07-25 | Ingene, Inc. | ENZYMATIC SYNTHESIS OF ssDNA |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| WO2000050050A1 (en) | 1999-02-23 | 2000-08-31 | Isis Pharmaceuticals, Inc. | Multiparticulate formulation |
| DE10100586C1 (de) | 2001-01-09 | 2002-04-11 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines Ziegens |
| IL155991A0 (en) | 2000-12-01 | 2003-12-23 | Max Planck Gesellschaft | Rna interference mediating small rna molecules |
| EP1386004A4 (en) | 2001-04-05 | 2005-02-16 | Ribozyme Pharm Inc | MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID |
| US20030170891A1 (en) | 2001-06-06 | 2003-09-11 | Mcswiggen James A. | RNA interference mediated inhibition of epidermal growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US7956176B2 (en) | 2002-09-05 | 2011-06-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| EP2305813A3 (en) | 2002-11-14 | 2012-03-28 | Dharmacon, Inc. | Fuctional and hyperfunctional sirna |
| US8110674B2 (en) | 2003-03-07 | 2012-02-07 | Alnylam Pharmaceuticals, Inc. | Therapeutic compositions |
| EP1608735A4 (en) | 2003-04-03 | 2008-11-05 | Alnylam Pharmaceuticals | RNAI CONJUGATES |
| US7598227B2 (en) * | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
| EP2660322A3 (en) * | 2003-04-17 | 2013-11-13 | Alnylam Pharmaceuticals Inc. | Modified iRNA agents |
| WO2004097429A2 (en) * | 2003-04-29 | 2004-11-11 | Biostratum, Inc. | Apociii and the treatmentand diagnosis of diabetes |
| US20050019927A1 (en) | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
| CN101291653B (zh) | 2003-07-16 | 2012-06-27 | 普洛体维生物治疗公司 | 脂质包封的干扰rna |
| TWI335352B (en) | 2005-03-31 | 2011-01-01 | Calando Pharmaceuticals Inc | Inhibitors of ribonucleotide reductase subunit 2 and uses thereof |
| CN101346393B (zh) | 2005-11-02 | 2015-07-22 | 普洛体维生物治疗公司 | 修饰的siRNA分子及其应用 |
| CA2873833A1 (en) * | 2006-03-31 | 2007-10-11 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of eg5 gene |
| JP2009537153A (ja) * | 2006-05-19 | 2009-10-29 | アルニラム ファーマシューティカルズ， インコーポレイテッド | ＡｈａのＲＮＡｉ調節およびその治療上の使用 |
| US8598333B2 (en) | 2006-05-26 | 2013-12-03 | Alnylam Pharmaceuticals, Inc. | SiRNA silencing of genes expressed in cancer |
| AU2007303205A1 (en) | 2006-10-03 | 2008-04-10 | Tekmira Pharmaceuticals Corporation | Lipid containing formulations |
| CN101702917A (zh) | 2007-03-30 | 2010-05-05 | 杜克大学 | 一种调节核酸分子活性的方法 |
| AR066984A1 (es) * | 2007-06-15 | 2009-09-23 | Novartis Ag | Inhibicion de la expresion de la subunidad alfa del canal epitelial de sodio (enac) por medio de arni (arn de interferencia) |
| ATE520414T1 (de) | 2007-06-18 | 2011-09-15 | Univ Oregon Health & Science | Protein c zur verwendung bei der aufrechterhaltung der hämostase |
| JP5635412B2 (ja) | 2007-12-04 | 2014-12-03 | アルニラム ファーマスーティカルズ インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 標的化脂質 |
| AU2009238175C1 (en) | 2008-04-15 | 2023-11-30 | Arbutus Biopharma Corporation | Novel lipid formulations for nucleic acid delivery |
| CN111909020A (zh) * | 2008-11-10 | 2020-11-10 | 阿布特斯生物制药公司 | 用于递送治疗剂的脂质和组合物 |
| AU2009324534B2 (en) * | 2008-12-10 | 2015-07-30 | Alnylam Pharmaceuticals, Inc. | GNAQ targeted dsRNA compositions and methods for inhibiting expression |
| CA2750561C (en) * | 2009-01-26 | 2017-10-10 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein c-iii expression |
| US20110071208A1 (en) * | 2009-06-05 | 2011-03-24 | Protiva Biotherapeutics, Inc. | Lipid encapsulated dicer-substrate interfering rna |
| CA2764609C (en) | 2009-06-10 | 2018-10-02 | Alnylam Pharmaceuticals, Inc. | Improved cationic lipid of formula i |
| WO2010147992A1 (en) | 2009-06-15 | 2010-12-23 | Alnylam Pharmaceuticals, Inc. | Methods for increasing efficacy of lipid formulated sirna |
| CN102458366B (zh) * | 2009-06-15 | 2015-02-11 | 阿尔尼拉姆医药品有限公司 | 靶向pcsk9基因的脂质配制的dsrna |
| EP2451940A4 (en) * | 2009-07-06 | 2013-08-28 | Alnylam Pharmaceuticals Inc | bioprocessing |
| WO2011030332A2 (en) | 2009-09-08 | 2011-03-17 | Yeda Research And Development Co. Ltd. | Methods for hematopoietic precursor mobilization |
| US9101643B2 (en) * | 2009-11-03 | 2015-08-11 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of transthyretin (TTR) |
| US8647825B2 (en) * | 2010-01-08 | 2014-02-11 | The Penn State Research Foundation | Compositions and methods relating to monitoring alcohol consumption and alcohol abuse |
| CN101921793A (zh) * | 2010-05-07 | 2010-12-22 | 德赛诊断系统(上海)有限公司 | 人载脂蛋白ai的基因工程制备方法及其表达载体和工程菌 |
| US10799808B2 (en) | 2018-09-13 | 2020-10-13 | Nina Davis | Interactive storytelling kit |
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