ES2573936T3 - Oligómeros para agentes terapéuticos - Google Patents
Oligómeros para agentes terapéuticos Download PDFInfo
- Publication number
- ES2573936T3 ES2573936T3 ES08780679.0T ES08780679T ES2573936T3 ES 2573936 T3 ES2573936 T3 ES 2573936T3 ES 08780679 T ES08780679 T ES 08780679T ES 2573936 T3 ES2573936 T3 ES 2573936T3
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- Prior art keywords
- rna
- monomers
- monomer
- complex
- hydroxymethyl
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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| PCT/US2008/064417 WO2008147824A2 (en) | 2007-05-22 | 2008-05-21 | Hydroxymethyl substituted rna oligonucleotides and rna complexes |
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Families Citing this family (219)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE44779E1 (en) | 1997-03-07 | 2014-02-25 | Santaris Pharma A/S | Bicyclonucleoside and oligonucleotide analogues |
| 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) |
| US9181551B2 (en) | 2002-02-20 | 2015-11-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| AU2007310982A1 (en) | 2006-10-18 | 2008-04-24 | Marina Biotech, Inc. | Nicked or gapped nucleic acid molecules and uses thereof |
| NZ580712A (en) * | 2007-05-22 | 2011-12-22 | Marina Biotech Inc | Hydroxymethyl substituted rna oligonucleotides and rna complexes containing acyclic monomers |
| US20100015708A1 (en) * | 2008-06-18 | 2010-01-21 | Mdrna, Inc. | Ribonucleic acids with non-standard bases and uses thereof |
| WO2010017319A2 (en) * | 2008-08-05 | 2010-02-11 | Mdrna, Inc. | Nucleic acid compounds for inhibiting plk1 gene expression and uses thereof |
| WO2010045512A2 (en) * | 2008-10-16 | 2010-04-22 | Mdrna , Inc. | Processes and compositions for liposomal and efficient delivery of gene silencing therapeutics |
| AU2009322290B2 (en) * | 2008-12-03 | 2016-06-16 | Arcturus Therapeutics, Inc. | Una oligomer structures for therapeutic agents |
| AU2010315124B2 (en) | 2009-11-04 | 2016-12-01 | Marina Biotech, Inc. | Activity generating delivery molecules |
| MX369004B (es) | 2009-12-18 | 2019-10-24 | Novartis Ag | Composiciones orgánicas para tratar las enfermedades relacionadas con hsf1. |
| EP2542678B1 (en) | 2010-03-04 | 2017-04-12 | InteRNA Technologies B.V. | A MiRNA MOLECULE DEFINED BY ITS SOURCE AND ITS THERAPEUTIC USES IN CANCER ASSOCIATED WITH EMT |
| WO2011133584A2 (en) * | 2010-04-19 | 2011-10-27 | Marina Biotech, Inc. | Nucleic acid compounds for inhibiting hras gene expression and uses thereof |
| US10913767B2 (en) | 2010-04-22 | 2021-02-09 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
| KR20180033606A (ko) | 2010-04-23 | 2018-04-03 | 애로우헤드 파마슈티컬스 인코포레이티드 | 베타-ENaC-관련 질환을 치료하기 위한 유기 조성물 |
| WO2011139843A2 (en) * | 2010-04-28 | 2011-11-10 | Marina Biotech, Inc. | Multi-sirna compositions for reducing gene expression |
| EP3369817A1 (en) | 2010-07-06 | 2018-09-05 | InteRNA Technologies B.V. | Mirna and its diagnostic and therapeutic uses in diseases or conditions associated with melanoma , or in diseases or conditions with activated braf pathway |
| JP6106085B2 (ja) | 2010-08-24 | 2017-03-29 | サーナ・セラピューティクス・インコーポレイテッドSirna Therapeutics,Inc. | 内部非核酸スペーサーを含む一本鎖RNAi剤 |
| DK2632472T3 (en) | 2010-10-29 | 2018-03-19 | Sirna Therapeutics Inc | RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA) |
| ES2639420T3 (es) | 2010-11-10 | 2017-10-26 | Nigel L. Webb | Nucliones y ribocápsides |
| EP2474617A1 (en) | 2011-01-11 | 2012-07-11 | InteRNA Technologies BV | Mir for treating neo-angiogenesis |
| CN102719434A (zh) * | 2011-03-31 | 2012-10-10 | 百奥迈科生物技术有限公司 | 抑制rna干扰脱靶效应的特异性修饰 |
| BR112014005103A2 (pt) | 2011-09-02 | 2017-07-04 | Novartis Ag | composições orgânicas para tratar doenças associadas com hsf1 |
| EP3369818B1 (en) | 2011-12-22 | 2021-06-09 | InteRNA Technologies B.V. | Mirna for treating head and neck cancer |
| JP6158833B2 (ja) | 2012-01-09 | 2017-07-05 | 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 | ベータ−カテニン関連疾患を処置するための有機組成物 |
| US10501512B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides |
| US10501513B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides for the production of oncology-related proteins and peptides |
| WO2013151665A2 (en) | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of proteins associated with human disease |
| EA201492004A1 (ru) | 2012-05-02 | 2015-08-31 | Новартис Аг | Органические композиции для лечения kras-ассоциированных заболеваний |
| EP3800256A1 (en) | 2012-11-06 | 2021-04-07 | InteRNA Technologies B.V. | Combination to be used in therapeutic use against diseases or conditions associated with melanoma, or in diseases or conditions associated with activated b-raf pathway |
| SG11201506805QA (en) | 2013-02-28 | 2015-09-29 | Arrowhead Res Corp | Organic compositions to treat epas1-related diseases |
| WO2015020960A1 (en) | 2013-08-09 | 2015-02-12 | Novartis Ag | Novel lncrna polynucleotides |
| WO2015023975A1 (en) * | 2013-08-16 | 2015-02-19 | Rana Therapeutics, Inc. | Compositions and methods for modulating rna |
| MX385871B (es) | 2013-10-02 | 2025-03-18 | Alnylam Pharmaceuticals Inc | Composiciones y metodos para inhibir la expresion del gen lect2. |
| HK1221912A1 (zh) | 2013-10-04 | 2017-06-16 | Novartis Ag | 用於治疗乙肝病毒的有机化合物 |
| WO2015051135A2 (en) | 2013-10-04 | 2015-04-09 | Novartis Ag | Organic compositions to treat hepcidin-related diseases |
| WO2015051044A2 (en) | 2013-10-04 | 2015-04-09 | Novartis Ag | Novel formats for organic compounds for use in rna interference |
| PE20161130A1 (es) | 2013-10-04 | 2016-11-25 | Icahn School Med Mount Sinai | Composiciones y metodos para inhibir la expresion del gen alas1 |
| US9988627B2 (en) | 2013-10-04 | 2018-06-05 | Novartis Ag | Formats for organic compounds for use in RNA interference |
| CA3188691A1 (en) | 2013-10-04 | 2015-04-09 | Novartis Ag | 3'end caps for rnai agents for use in rna interference |
| BR112016013148B1 (pt) | 2013-12-12 | 2024-02-27 | Alnylam Pharmaceuticals, Inc | ÁCIDO RIBONUCLEICO DE FITA DUPLA (dsRNA) PARA INIBIÇÃO DA EXPRESSÃO DO FATOR B DO COMPLEMENTO (CFB) EM UMA CÉLULA, COMPOSIÇÃO FARMACÊUTICA PARA INIBIÇÃO DA EXPRESSÃO DE UM GENE DO FATOR B DO COMPLEMENTO, SEU USO, E MÉTODO IN VITRO DE INIBIÇÃO DA EXPRESSÃO DO FATOR B DO COMPLEMENTO (CFB) EM UMA CÉLULA |
| EA201691587A1 (ru) | 2014-02-11 | 2017-01-30 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ НА ОСНОВЕ iRNA ДЛЯ КЕТОГЕКСОКИНАЗЫ (KHK) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| CN106460025A (zh) | 2014-03-25 | 2017-02-22 | 阿克丘勒斯治疗公司 | 在基因沉默中具有降低的脱靶效应的una寡聚物 |
| US9856475B2 (en) | 2014-03-25 | 2018-01-02 | Arcturus Therapeutics, Inc. | Formulations for treating amyloidosis |
| WO2015148582A1 (en) | 2014-03-25 | 2015-10-01 | Arcturus Therapeutics, Inc. | Transthyretin allele selective una oligomers for gene silencing |
| TW201607559A (zh) | 2014-05-12 | 2016-03-01 | 阿尼拉製藥公司 | 治療serpinc1相關疾患之方法和組成物 |
| WO2015179724A1 (en) | 2014-05-22 | 2015-11-26 | Alnylam Pharmaceuticals, Inc. | Angiotensinogen (agt) irna compositions and methods of use thereof |
| TW201620526A (zh) | 2014-06-17 | 2016-06-16 | 愛羅海德研究公司 | 用於抑制α-1抗胰蛋白酶基因表現之組合物及方法 |
| CN106794141B (zh) | 2014-07-16 | 2021-05-28 | 诺华股份有限公司 | 将核酸包封在脂质纳米粒主体中的方法 |
| WO2016011123A1 (en) | 2014-07-16 | 2016-01-21 | Arrowhead Research Corporation | Organic compositions to treat apoc3-related diseases |
| EP3191591A1 (en) | 2014-09-12 | 2017-07-19 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting complement component c5 and methods of use thereof |
| CN107208095B (zh) | 2014-10-02 | 2021-11-16 | 阿布特斯生物制药公司 | 用于使乙型肝炎病毒基因表达沉默的组合物和方法 |
| WO2016061487A1 (en) | 2014-10-17 | 2016-04-21 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof |
| EP3212794B1 (en) | 2014-10-30 | 2021-04-07 | Genzyme Corporation | Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof |
| AU2015338923B2 (en) * | 2014-11-02 | 2021-10-21 | Arcturus Therapeutics, Inc. | Messenger UNA molecules and uses thereof |
| JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
| WO2016081444A1 (en) | 2014-11-17 | 2016-05-26 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof |
| US10758558B2 (en) | 2015-02-13 | 2020-09-01 | Translate Bio Ma, Inc. | Hybrid oligonucleotides and uses thereof |
| AU2016219263B2 (en) | 2015-02-13 | 2022-12-01 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (PNPLA3) iRNA compositions and methods of use thereof |
| US10519447B2 (en) | 2015-04-01 | 2019-12-31 | Arcturus Therapeutics, Inc. | Therapeutic UNA oligomers and uses thereof |
| US10745702B2 (en) | 2015-04-08 | 2020-08-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the LECT2 gene |
| WO2016197132A1 (en) | 2015-06-04 | 2016-12-08 | Protiva Biotherapeutics Inc. | Treating hepatitis b virus infection using crispr |
| EP4365291A3 (en) | 2015-06-12 | 2024-08-14 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions and methods of use thereof |
| WO2016205323A1 (en) | 2015-06-18 | 2016-12-22 | Alnylam Pharmaceuticals, Inc. | Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof |
| WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
| US10494632B2 (en) | 2015-07-10 | 2019-12-03 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (IGFALS) compositions and methods of use thereof |
| AU2016296592B2 (en) | 2015-07-17 | 2021-08-19 | Arcturus Therapeutics, Inc. | Compositions and agents against Hepatitis B virus and uses thereof |
| WO2017015671A1 (en) | 2015-07-23 | 2017-01-26 | Arcturus Therapeutics, Inc. | Compositions for treating amyloidosis |
| WO2017019891A2 (en) | 2015-07-29 | 2017-02-02 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing hepatitis b virus gene expression |
| EP4393495A3 (en) | 2015-09-02 | 2024-09-25 | Alnylam Pharmaceuticals, Inc. | Programmed cell death 1 ligand 1 (pd-l1) irna compositions and methods of use thereof |
| ES2959815T3 (es) | 2015-09-21 | 2024-02-28 | Arcturus Therapeutics Inc | Edición génica selectiva de alelo y usos de la misma |
| IL308717A (en) | 2015-12-07 | 2024-01-01 | Genzyme Corp | Methods and compositions for treating a serpinc1-associated disorder |
| MA45295A (fr) | 2016-04-19 | 2019-02-27 | Alnylam Pharmaceuticals Inc | Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser |
| TWI815794B (zh) | 2016-06-06 | 2023-09-21 | 美商愛羅海德製藥公司 | 5’-環-磷酸修飾之核苷酸 |
| WO2017214518A1 (en) | 2016-06-10 | 2017-12-14 | Alnylam Pharmaceuticals, Inc. | COMPLETMENT COMPONENT C5 iRNA COMPOSTIONS AND METHODS OF USE THEREOF FOR TREATING PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) |
| AU2017286980B2 (en) | 2016-06-30 | 2023-10-26 | Arbutus Biopharma Corporation | Compositions and methods for delivering messenger RNA |
| US10781175B2 (en) | 2016-07-15 | 2020-09-22 | Am Chemicals Llc | Solid supports and phosphoramidite building blocks for oligonucleotide conjugates |
| MA45999A (fr) | 2016-08-22 | 2019-06-26 | Arbutus Biopharma Corp | Anticorps anti-pd-1, ou leurs fragments, pour le traitement de l'hépatite b |
| US10487105B2 (en) | 2016-10-19 | 2019-11-26 | Arcturus Therapeutics, Inc. | Trinucleotide MRNA cap analogs |
| TW202313978A (zh) | 2016-11-23 | 2023-04-01 | 美商阿尼拉製藥公司 | 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法 |
| JP7058656B2 (ja) | 2016-12-16 | 2022-04-22 | 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 | トランスサイレチン(TTR)iRNA組成物を用いてTTR関連疾患を治療または予防するための方法 |
| EP3568482A4 (en) | 2017-01-10 | 2020-12-16 | Arrowhead Pharmaceuticals, Inc. | ALPHA-1 ANTITRYPSIN (AAT) RNA INTERFERENCE (RNA) AGENTS, COMPOSITIONS CONTAINING THEM, AND PROCEDURES FOR USE THEREOF |
| TWI843703B (zh) | 2017-07-10 | 2024-06-01 | 美商健贊公司 | 於患有血友病之個體中治療出血事件之方法及組成物 |
| CA3074303A1 (en) | 2017-09-11 | 2019-03-14 | Arrowhead Pharmaceuticals, Inc. | Rnai agents and compositions for inhibiting expression of apolipoprotein c-iii (apoc3) |
| CA3077213A1 (en) | 2017-10-04 | 2019-04-11 | Avidity Biosciences, Inc. | Nucleic acid-polypeptide compositions and uses thereof |
| US11497762B2 (en) | 2017-11-03 | 2022-11-15 | Interna Technologies B.V. | MiRNA molecule, equivalent, antagomir, or source thereof for treating and/or diagnosing a condition and/or a disease associated with neuronal deficiency or for neuronal (re)generation |
| US20200385719A1 (en) | 2017-11-16 | 2020-12-10 | Alnylam Pharmaceuticals, Inc. | Kisspeptin 1 (kiss1) irna compositions and methods of use thereof |
| CA3086343A1 (en) | 2017-12-18 | 2019-06-27 | Alnylam Pharmaceuticals, Inc. | High mobility group box-1 (hmgb1) irna compositions and methods of use thereof |
| EP3752164A1 (en) | 2018-02-12 | 2020-12-23 | InteRNA Technologies B.V. | Anticancer microrna and lipid formulations thereof |
| US12083224B2 (en) | 2018-03-30 | 2024-09-10 | Arcturus Therapeutics, Inc. | Lipid particles for nucleic acid delivery |
| TWI851574B (zh) | 2018-05-14 | 2024-08-11 | 美商阿尼拉製藥公司 | 血管收縮素原(AGT)iRNA組成物及其使用方法 |
| EP3833397A4 (en) | 2018-08-08 | 2023-06-14 | Arcturus Therapeutics, Inc. | COMPOSITIONS AND AGENTS AGAINST NON-ALCOHOLIC STEATOHEPATITIS |
| JP2021534101A (ja) | 2018-08-09 | 2021-12-09 | ヴェルソー セラピューティクス, インコーポレイテッド | Ccr2及びcsf1rを標的とするためのオリゴヌクレオチド組成物ならびにその使用 |
| MY201997A (en) | 2018-08-13 | 2024-03-28 | Alnylam Pharmaceuticals Inc | Hepatitis b virus (hbv) dsrna agent compositions and methods of use thereof |
| AR115960A1 (es) | 2018-08-16 | 2021-03-17 | Alnylam Pharmaceuticals Inc | Composiciones y métodos para inhibir la expresión del gen lect2 |
| US12281308B2 (en) | 2018-08-29 | 2025-04-22 | University Of Massachusetts | Inhibition of protein kinases to treat Friedreich ataxia |
| JP2022500003A (ja) | 2018-09-18 | 2022-01-04 | 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. | ケトヘキソキナーゼ(KHK)iRNA組成物およびその使用方法 |
| US10913951B2 (en) | 2018-10-31 | 2021-02-09 | University of Pittsburgh—of the Commonwealth System of Higher Education | Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure |
| WO2020117706A1 (en) | 2018-12-03 | 2020-06-11 | Triplet Therapeutics, Inc. | Methods for the treatment of trinucleotide repeat expansion disorders associated with mlh3 activity |
| CN113631709A (zh) | 2018-12-20 | 2021-11-09 | 普拉克西斯精密药物股份有限公司 | 用于治疗kcnt1相关病症的组合物和方法 |
| SG11202105577TA (en) | 2019-01-09 | 2021-06-29 | Arrowhead Pharmaceuticals Inc | Rnai agents for inhibiting expression of hif-2 alpha (epas1), compositions thereof, and methods of use |
| TW202043471A (zh) | 2019-01-16 | 2020-12-01 | 美商健贊公司 | SERPINC1 iRNA組成物及其使用方法 |
| US12215382B2 (en) | 2019-03-01 | 2025-02-04 | The General Hospital Corporation | Liver protective MARC variants and uses thereof |
| KR20220024419A (ko) | 2019-06-06 | 2022-03-03 | 어비디티 바이오사이언시스 인크. | 핵산-폴리펩티드 조성물 및 이의 용도 |
| JP7581252B2 (ja) * | 2019-06-06 | 2024-11-12 | アビディティー バイオサイエンシーズ,インク. | Unaアミダイトおよびその使用 |
| WO2021022109A1 (en) | 2019-08-01 | 2021-02-04 | Alnylam Pharmaceuticals, Inc. | SERPIN FAMILY F MEMBER 2 (SERPINF2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2021022108A2 (en) | 2019-08-01 | 2021-02-04 | Alnylam Pharmaceuticals, Inc. | CARBOXYPEPTIDASE B2 (CPB2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2021030522A1 (en) | 2019-08-13 | 2021-02-18 | Alnylam Pharmaceuticals, Inc. | SMALL RIBOSOMAL PROTEIN SUBUNIT 25 (RPS25) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2021046122A1 (en) | 2019-09-03 | 2021-03-11 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the lect2 gene |
| EP4025582A1 (en) * | 2019-09-05 | 2022-07-13 | Sanofi | Oligonucleotides containing nucleotide analogs |
| WO2021067747A1 (en) | 2019-10-04 | 2021-04-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing ugt1a1 gene expression |
| WO2021076828A1 (en) | 2019-10-18 | 2021-04-22 | Alnylam Pharmaceuticals, Inc. | Solute carrier family member irna compositions and methods of use thereof |
| JP7676377B2 (ja) | 2019-10-22 | 2025-05-14 | 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 | 補体成分C3 iRNA組成物およびその使用方法 |
| US20230040920A1 (en) | 2019-11-01 | 2023-02-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing dnajb1-prkaca fusion gene expression |
| JP2023500661A (ja) | 2019-11-01 | 2023-01-10 | 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 | ハンチンチン(HTT)iRNA剤組成物およびその使用方法 |
| WO2021102373A1 (en) | 2019-11-22 | 2021-05-27 | Alnylam Pharmaceuticals, Inc. | Ataxin3 (atxn3) rnai agent compositions and methods of use thereof |
| EP4073251A1 (en) | 2019-12-13 | 2022-10-19 | Alnylam Pharmaceuticals, Inc. | Human chromosome 9 open reading frame 72 (c9orf72) irna agent compositions and methods of use thereof |
| WO2021126734A1 (en) | 2019-12-16 | 2021-06-24 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
| TW202140786A (zh) | 2020-02-10 | 2021-11-01 | 美商艾爾妮蘭製藥公司 | 用於靜默vegf-a表現之組合物及方法 |
| AU2021224778A1 (en) | 2020-02-18 | 2022-09-29 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein C3 (APOC3) iRNA compositions and methods of use thereof |
| EP4114947A1 (en) | 2020-03-05 | 2023-01-11 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
| AU2021232014A1 (en) | 2020-03-06 | 2022-10-06 | Alnylam Pharmaceuticals, Inc. | Ketohexokinase (KHK) IRNA compositions and methods of use thereof |
| WO2021188611A1 (en) | 2020-03-18 | 2021-09-23 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant |
| JP2023519274A (ja) | 2020-03-26 | 2023-05-10 | 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 | コロナウイルスiRNA組成物およびその使用方法 |
| WO2021202443A2 (en) | 2020-03-30 | 2021-10-07 | Alnylam Pharmaceucticals, Inc. | Compositions and methods for silencing dnajc15 gene expression |
| US12534731B2 (en) | 2020-04-01 | 2026-01-27 | Alnylam Pharmaceuticals, Inc. | Alpha-2A adrenergic receptor (ADRA2A) iRNA agent compositions and methods of use thereof |
| JP2023520582A (ja) | 2020-04-06 | 2023-05-17 | 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 | Myoc発現をサイレンシングするための組成物および方法 |
| EP4133077A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
| AU2021251754A1 (en) | 2020-04-07 | 2022-11-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing SCN9A expression |
| WO2021206917A1 (en) | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
| CN115955972A (zh) | 2020-04-27 | 2023-04-11 | 阿尔尼拉姆医药品有限公司 | 载脂蛋白E(APOE)iRNA剂组合物及其使用方法 |
| MX2022013606A (es) | 2020-04-30 | 2023-01-16 | Alnylam Pharmaceuticals Inc | Composiciones de ácido ribonucleico interferente (arni) del factor b de complemento (cfb) y métodos de uso de las mismas. |
| EP4150077A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1) |
| EP4150087A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2) |
| EP4150086A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2) |
| WO2021231698A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl) |
| WO2021231675A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1) |
| WO2021231692A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of otoferlin (otof) |
| WO2021231691A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of retinoschisin 1 (rsi) |
| EP4150076A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2) |
| US20230183707A1 (en) | 2020-05-21 | 2023-06-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting marc1 gene expression |
| AR122534A1 (es) | 2020-06-03 | 2022-09-21 | Triplet Therapeutics Inc | Métodos para el tratamiento de los trastornos de expansión por repetición de nucleótidos asociados con la actividad de msh3 |
| WO2021252557A1 (en) | 2020-06-09 | 2021-12-16 | Alnylam Pharmaceuticals, Inc. | Rnai compositions and methods of use thereof for delivery by inhalation |
| CN116075592A (zh) | 2020-06-09 | 2023-05-05 | 阿尔尼拉姆医药品有限公司 | 用于沉默gpam(线粒体甘油-3-磷酸酰基转移酶1)表达的sirna组合物和方法 |
| MX2022015149A (es) | 2020-06-18 | 2023-01-11 | Alnylam Pharmaceuticals Inc | Composiciones de acido ribonucleico de interferencia (arni) de xantina dehidrogenasa (xdh) y metodos de uso de las mismas. |
| TW202227102A (zh) | 2020-09-22 | 2022-07-16 | 瑞典商阿斯特捷利康公司 | 治療脂肪肝病之方法 |
| EP4217489A1 (en) | 2020-09-24 | 2023-08-02 | Alnylam Pharmaceuticals, Inc. | Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof |
| EP4225917A1 (en) | 2020-10-05 | 2023-08-16 | Alnylam Pharmaceuticals, Inc. | G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof |
| EP4232582A1 (en) | 2020-10-23 | 2023-08-30 | Alnylam Pharmaceuticals, Inc. | Mucin 5b (muc5b) irna compositions and methods of use thereof |
| CA3200595A1 (en) | 2020-11-13 | 2022-05-19 | Alnylam Pharmaceuticals, Inc. | Coagulation factor v (f5) irna compositions and methods of use thereof |
| EP4259795A1 (en) | 2020-12-08 | 2023-10-18 | Alnylam Pharmaceuticals, Inc. | Coagulation factor x (f10) irna compositions and methods of use thereof |
| EP4274896A1 (en) | 2021-01-05 | 2023-11-15 | Alnylam Pharmaceuticals, Inc. | Complement component 9 (c9) irna compositions and methods of use thereof |
| CA3210763A1 (en) | 2021-02-12 | 2022-08-18 | Alnylam Pharmaceuticals, Inc. | Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases |
| CN117222739A (zh) | 2021-02-25 | 2023-12-12 | 阿尔尼拉姆医药品有限公司 | 朊病毒蛋白(prnp)irna组合物和其使用方法 |
| BR112023016645A2 (pt) | 2021-02-26 | 2023-11-14 | Alnylam Pharmaceuticals Inc | Composições de irna de ceto-hexoquinase (khk) e métodos de uso das mesmas |
| IL305442A (en) | 2021-03-04 | 2023-10-01 | Alnylam Pharmaceuticals Inc | Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them |
| EP4305169A1 (en) | 2021-03-12 | 2024-01-17 | Alnylam Pharmaceuticals, Inc. | Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof |
| BR112023019981A2 (pt) | 2021-03-29 | 2023-12-12 | Alnylam Pharmaceuticals Inc | Composições do agente irna de huntingtina (htt) e métodos de uso das mesmas |
| WO2022212153A1 (en) | 2021-04-01 | 2022-10-06 | Alnylam Pharmaceuticals, Inc. | Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof |
| KR20240001207A (ko) | 2021-04-26 | 2024-01-03 | 알닐람 파마슈티칼스 인코포레이티드 | 막관통 프로테아제, 세린 6(TMPRSS6) iRNA 조성물 및 이의 사용 방법 |
| EP4330396A1 (en) | 2021-04-29 | 2024-03-06 | Alnylam Pharmaceuticals, Inc. | Signal transducer and activator of transcription factor 6 (stat6) irna compositions and methods of use thereof |
| WO2022245583A1 (en) | 2021-05-18 | 2022-11-24 | Alnylam Pharmaceuticals, Inc. | Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof |
| EP4341405A1 (en) | 2021-05-20 | 2024-03-27 | Korro Bio, Inc. | Methods and compositions for adar-mediated editing |
| WO2022256283A2 (en) | 2021-06-01 | 2022-12-08 | Korro Bio, Inc. | Methods for restoring protein function using adar |
| JP2024522996A (ja) | 2021-06-02 | 2024-06-25 | 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 | パタチン様ホスホリパーゼドメイン含有3(PNPLA3)iRNA組成物およびその使用方法 |
| IL308743A (en) | 2021-06-04 | 2024-01-01 | Alnylam Pharmaceuticals Inc | Compositions of human chromosome 9 open reading frame 72 iRNA factor (C9ORF72) and methods of using them |
| WO2022260939A2 (en) | 2021-06-08 | 2022-12-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders |
| EP4363574A1 (en) | 2021-06-29 | 2024-05-08 | Korro Bio, Inc. | Methods and compositions for adar-mediated editing |
| US20230194709A9 (en) | 2021-06-29 | 2023-06-22 | Seagate Technology Llc | Range information detection using coherent pulse sets with selected waveform characteristics |
| JP2024528659A (ja) | 2021-07-19 | 2024-07-30 | 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 | 非原発性高シュウ酸尿症疾患または障害を有するまたは発症するリスクがある対象を治療するための方法および組成物 |
| AU2022316139A1 (en) | 2021-07-23 | 2024-01-18 | Alnylam Pharmaceuticals, Inc. | Beta-catenin (ctnnb1) irna compositions and methods of use thereof |
| EP4377458A1 (en) | 2021-07-29 | 2024-06-05 | Alnylam Pharmaceuticals, Inc. | 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof |
| EP4381067A1 (en) | 2021-08-03 | 2024-06-12 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof |
| AU2022324003A1 (en) | 2021-08-04 | 2024-02-08 | Alnylam Pharmaceuticals, Inc. | iRNA COMPOSITIONS AND METHODS FOR SILENCING ANGIOTENSINOGEN (AGT) |
| CA3228733A1 (en) | 2021-08-13 | 2023-02-16 | Alnylam Pharmaceuticals, Inc. | Factor xii (f12) irna compositions and methods of use thereof |
| WO2023034837A2 (en) | 2021-08-31 | 2023-03-09 | Alnylam Pharmaceuticals, Inc. | Cell death-inducing dffa-like effector b (cideb) irna compositions and methods of use thereof |
| EP4401742A2 (en) | 2021-09-17 | 2024-07-24 | Alnylam Pharmaceuticals, Inc. | Irna compositions and methods for silencing complement component 3 (c3) |
| IL311454A (en) | 2021-09-20 | 2024-05-01 | Alnylam Pharmaceuticals Inc | Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof |
| KR20240067943A (ko) | 2021-09-24 | 2024-05-17 | 알닐람 파마슈티칼스 인코포레이티드 | 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법 |
| CN118922540A (zh) | 2021-10-01 | 2024-11-08 | 阿达尔克斯制药有限公司 | 前激肽释放酶调节组合物及其使用方法 |
| EP4419683A1 (en) | 2021-10-22 | 2024-08-28 | Korro Bio, Inc. | Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing |
| EP4423272A2 (en) | 2021-10-29 | 2024-09-04 | Alnylam Pharmaceuticals, Inc. | Huntingtin (htt) irna agent compositions and methods of use thereof |
| CA3234636A1 (en) | 2021-10-29 | 2023-05-04 | Alnylam Pharmaceuticals, Inc. | Complement factor b (cfb) irna compositions and methods of use thereof |
| WO2023122762A1 (en) | 2021-12-22 | 2023-06-29 | Camp4 Therapeutics Corporation | Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas |
| EP4469575A2 (en) | 2022-01-24 | 2024-12-04 | Alnylam Pharmaceuticals, Inc. | Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof |
| WO2023240277A2 (en) | 2022-06-10 | 2023-12-14 | Camp4 Therapeutics Corporation | Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas |
| JP2025527531A (ja) | 2022-08-18 | 2025-08-22 | 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 | ユニバーサル非標的sirna組成物およびその使用方法 |
| CN119907856A (zh) | 2022-09-15 | 2025-04-29 | 阿尔尼拉姆医药品有限公司 | 第13型17β-羟基类固醇脱氢酶(HSD17B13)iRNA组合物及其使用方法 |
| EP4627084A1 (en) | 2022-12-01 | 2025-10-08 | Camp4 Therapeutics Corporation | Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas |
| IT202200026595A1 (it) | 2022-12-22 | 2024-06-22 | Fond Telethon Ets | Nuovi inibitori di regolatori epigenetici |
| WO2024168010A2 (en) | 2023-02-09 | 2024-08-15 | Alnylam Pharmaceuticals, Inc. | Reversir molecules and methods of use thereof |
| EP4678646A1 (en) | 2023-04-06 | 2026-01-14 | Shanghai Argo Biopharmaceutical Co., Ltd. | Nucleoside analog for 5'-phosphonate modification and oligonucleotide prepared therefrom |
| AU2024258561A1 (en) | 2023-04-20 | 2025-10-30 | Adarx Pharmaceuticals, Inc. | Mapt-modulating compositions and methods of use thereof |
| WO2024220746A2 (en) | 2023-04-21 | 2024-10-24 | Flagship Pioneering Innovations Vii, Llc | Rnai agents targeting fatty acid synthase and related methods |
| TW202502385A (zh) | 2023-05-12 | 2025-01-16 | 美商雅迪克斯製藥公司 | Nmda配位體結合之化合物及其用途 |
| WO2024235124A1 (zh) * | 2023-05-12 | 2024-11-21 | 北京炫景瑞医药科技有限公司 | 修饰的核苷类似物及其用途与含核苷酸类似物的双链寡核苷酸及其用途 |
| WO2024249328A2 (en) | 2023-05-26 | 2024-12-05 | Adarx Pharmaceuticals, Inc. | Sod1-modulating compositions and methods of use thereof |
| WO2024263694A1 (en) | 2023-06-20 | 2024-12-26 | Adarx Pharmaceuticals, Inc. | Lrrk2-modulating compositions and methods of use thereof |
| AU2024287308A1 (en) | 2023-07-13 | 2025-12-18 | Korro Bio, Inc. | Rna-editing oligonucleotides and uses thereof |
| AU2024299328A1 (en) | 2023-07-21 | 2026-01-22 | Marrow Therapeutics, Inc. | Hematopoietic cell targeting conjugates and related methods |
| TW202519653A (zh) | 2023-07-25 | 2025-05-16 | 美商旗艦先鋒創新有限責任(Vii)公司 | Cas內切酶及相關方法 |
| US20250092426A1 (en) | 2023-07-25 | 2025-03-20 | Flagship Pioneering Innovations Vii, Llc | Cas endonucleases and related methods |
| WO2025034422A1 (en) | 2023-08-04 | 2025-02-13 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating ctnnb1-associated disorders |
| WO2025072331A1 (en) | 2023-09-26 | 2025-04-03 | Flagship Pioneering Innovations Vii, Llc | Cas nucleases and related methods |
| GB202314724D0 (en) | 2023-09-26 | 2023-11-08 | Astrazeneca Ab | compounds and methods for reducing psd3 expression |
| WO2025072699A1 (en) | 2023-09-27 | 2025-04-03 | Judo Bio, Inc. | Aminoglycosides for delivery of agents to the kidney |
| WO2025072713A1 (en) | 2023-09-27 | 2025-04-03 | Judo Bio, Inc. | Polymyxins for delivery of agents to the kidney |
| WO2025072672A2 (en) | 2023-09-27 | 2025-04-03 | Judo Bio, Inc. | Slc6a19-targeting modulatory nucleic acid agents |
| WO2025076031A2 (en) | 2023-10-03 | 2025-04-10 | Alnylam Pharmaceuticals, Inc. | Peritoneal macrophages comprising a nanoparticle encapsulating a nucleic acid molecule and methods of use thereof |
| WO2025096809A1 (en) | 2023-10-31 | 2025-05-08 | Korro Bio, Inc. | Oligonucleotides comprising phosphoramidate internucleotide linkages |
| WO2025117877A2 (en) | 2023-12-01 | 2025-06-05 | Flagship Pioneering Innovations Vii, Llc | Cas nucleases and related methods |
| WO2025128799A1 (en) | 2023-12-12 | 2025-06-19 | Korro Bio, Inc. | Double-stranded rna-editing oligonucleotides and uses thereof |
| WO2025140551A1 (en) | 2023-12-29 | 2025-07-03 | Neuro3 Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR TREATING NaV1.7 (SCN9A) -ASSOCIATED DISORDERS |
| US20250263702A1 (en) | 2024-02-19 | 2025-08-21 | Flagship Pioneering Innovations Vii, Llc | Rnai agents targeting cideb and related methods |
| US20250313840A1 (en) | 2024-03-20 | 2025-10-09 | Vertex Pharmaceuticals Incorporated | Mucin-5b (muc5b) targeted sirna and antisense oligonucleotides and methods of use thereof |
| WO2025217275A2 (en) | 2024-04-10 | 2025-10-16 | Flagship Pioneering Innovations Vii, Llc | Immune cell targeted compositions and related methods |
| WO2025255388A1 (en) | 2024-06-05 | 2025-12-11 | Camp4 Therapeutics Corporation | Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas |
| WO2025259747A2 (en) | 2024-06-12 | 2025-12-18 | Alnylam Pharmaceuticals, Inc. | Dystrophy myotonic protein kinase (dmpk) irna compositions and methods of use thereof |
| WO2025259743A1 (en) | 2024-06-12 | 2025-12-18 | Alnylam Pharmaceuticals, Inc. | Dual conjugate compounds for extrahepatic delivery |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4199574A (en) | 1974-09-02 | 1980-04-22 | Burroughs Wellcome Co. | Methods and compositions for treating viral infections and guanine acyclic nucleosides |
| US4968686A (en) | 1988-04-08 | 1990-11-06 | The Regents Of The University Of Michigan | Acyclic pyrrolo [2,3-d]pyrimidine analogs as antiviral agents |
| US5652355A (en) * | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
| US5786359A (en) | 1994-05-27 | 1998-07-28 | The Scripps Research Institute | N9 alkyl or aralkyl derivatives of 7, 8-disubstituted guanines |
| US6608035B1 (en) | 1994-10-25 | 2003-08-19 | Hybridon, Inc. | Method of down-regulating gene expression |
| GB9505025D0 (en) | 1995-03-13 | 1995-05-03 | Medical Res Council | Chemical compounds |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| US6069132A (en) | 1996-08-14 | 2000-05-30 | Revanker; Ganapathi R. | Phosphazole compounds |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| US7098192B2 (en) * | 1999-04-08 | 2006-08-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of STAT3 expression |
| US6037176A (en) | 1999-06-25 | 2000-03-14 | Isis Pharmaceuticals Inc. | Antisense inhibition of integrin beta 3 expression |
| GB9925459D0 (en) | 1999-10-27 | 1999-12-29 | Plant Bioscience Ltd | Gene silencing |
| US7829693B2 (en) | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
| WO2002081628A2 (en) | 2001-04-05 | 2002-10-17 | Ribozyme Pharmaceuticals, Incorporated | Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies |
| WO2003070918A2 (en) | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | Rna interference by modified short interfering nucleic acid |
| US8202979B2 (en) | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
| KR20080023768A (ko) | 2000-03-30 | 2008-03-14 | 화이트헤드 인스티튜트 포 바이오메디칼 리서치 | Rna 간섭의 rna 서열 특이적인 매개체 |
| CZ302719B6 (cs) | 2000-12-01 | 2011-09-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Izolovaná molekula dvouretezcové RNA, zpusob její výroby a její použití |
| US8546143B2 (en) | 2001-01-09 | 2013-10-01 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
| WO2007022369A2 (en) * | 2005-08-17 | 2007-02-22 | Sirna Therapeutics, Inc. | Chemically modified short interfering nucleic acid molecules that mediate rna interference |
| CA2452458A1 (en) | 2001-07-03 | 2003-01-16 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
| CA2921821A1 (en) | 2001-07-12 | 2003-01-23 | University Of Massachusetts | In vivo production of small interfering rnas that mediate gene silencing |
| MXPA04004056A (es) * | 2001-10-29 | 2004-09-10 | Univ Mcgill | Oligonucleotidos que contienen enlazador aciclico y usos de los mismos. |
| US7388002B2 (en) | 2001-11-14 | 2008-06-17 | Biocryst Pharmaceuticals, Inc. | Nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases |
| US7897753B2 (en) | 2002-02-20 | 2011-03-01 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of XIAP gene expression using short interfering nucleic acid (siNA) |
| AU2003248708A1 (en) | 2002-06-17 | 2003-12-31 | Isis Pharmaceuticals, Inc. | Oligomeric compounds that include carbocyclic nucleosides and their use in gene modulation |
| 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) |
| WO2004041889A2 (en) | 2002-11-05 | 2004-05-21 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| CA2518475C (en) | 2003-03-07 | 2014-12-23 | Alnylam Pharmaceuticals, Inc. | Irna agents comprising asymmetrical modifications |
| JP4605799B2 (ja) | 2003-04-02 | 2011-01-05 | ダーマコン, インコーポレイテッド | Rna干渉において使用するための修飾ポリヌクレオチド |
| EP1608735A4 (en) | 2003-04-03 | 2008-11-05 | Alnylam Pharmaceuticals | RNAI CONJUGATES |
| ES2702942T3 (es) | 2003-04-17 | 2019-03-06 | Alnylam Pharmaceuticals Inc | Agentes de ARNi modificados |
| AU2004248136B2 (en) | 2003-06-02 | 2011-09-15 | University Of Massachusetts | Methods and compositions for controlling efficacy of RNA silencing |
| US7750144B2 (en) | 2003-06-02 | 2010-07-06 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
| ES2905724T3 (es) | 2003-06-13 | 2022-04-11 | Alnylam Europe Ag | Acido ribonucleico bicatenario con elevada eficacia en un organismo |
| EP2700720A3 (en) | 2004-03-15 | 2015-01-28 | Isis Pharmaceuticals, Inc. | Compositions and methods for optimizing cleavage of RNA by RNASE H |
| WO2005089287A2 (en) * | 2004-03-15 | 2005-09-29 | City Of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded rna |
| KR101147147B1 (ko) | 2004-04-01 | 2012-05-25 | 머크 샤프 앤드 돔 코포레이션 | Rna 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드 |
| AU2005323437B2 (en) | 2004-04-30 | 2011-10-06 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a C5-modified pyrimidine |
| EP1766071A4 (en) * | 2004-06-03 | 2009-11-11 | Isis Pharmaceuticals Inc | DOUBLE-STRONG COMPOSITIONS WITH DIFFERENTLY MODIFIED STRANDS FOR USE IN GENE MODULATION |
| CA2572151A1 (en) | 2004-06-30 | 2006-08-24 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a non-phosphate backbone linkage |
| US7297786B2 (en) * | 2004-07-09 | 2007-11-20 | University Of Iowa Research Foundation | RNA interference in respiratory epitheial cells |
| WO2006093526A2 (en) | 2004-07-21 | 2006-09-08 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a modified or non-natural nucleobase |
| WO2006112872A2 (en) | 2004-08-04 | 2006-10-26 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase |
| AU2006308765B2 (en) * | 2005-11-02 | 2013-09-05 | Arbutus Biopharma Corporation | Modified siRNA molecules and uses thereof |
| US7915399B2 (en) | 2006-06-09 | 2011-03-29 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
| NZ580712A (en) * | 2007-05-22 | 2011-12-22 | Marina Biotech Inc | Hydroxymethyl substituted rna oligonucleotides and rna complexes containing acyclic monomers |
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