JP7424728B2 - Ｒｎａ干渉のための長鎖の二本鎖ｒｎａ - Google Patents
Ｒｎａ干渉のための長鎖の二本鎖ｒｎａ Download PDFInfo
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| DK2631291T3 (da) | 2010-10-22 | 2019-06-11 | Olix Pharmaceuticals Inc | Nukleinsyremolekyler, der inducerer rna-interferens, og anvendelser deraf |
| KR101567576B1 (ko) | 2012-05-22 | 2015-11-10 | 올릭스 주식회사 | 세포 내 관통능을 가지고 ｒｎａ 간섭을 유도하는 핵산 분자 및 그 용도 |
| JP7027311B2 (ja) | 2015-11-16 | 2022-03-01 | オリックス ファーマシューティカルズ，インコーポレーテッド | ＭｙＤ８８又はＴＬＲ３を標的とするＲＮＡ複合体を使用した加齢黄斑変性の治療 |
| JP6944942B2 (ja) | 2016-02-02 | 2021-10-06 | オリックス ファーマシューティカルズ，インコーポレーテッド | ＩＬ４Ｒα、ＴＲＰＡ１、またはＦ２ＲＬ１を標的とするＲＮＡ複合体を用いたアトピー性皮膚炎および喘息の治療 |
| CN108779464B (zh) | 2016-02-02 | 2022-05-17 | 奥利克斯医药有限公司 | 使用靶向angpt2和pdgfb的rna复合物治疗血管生成相关性疾病 |
| JP7049262B2 (ja) | 2016-04-11 | 2022-04-06 | オリックス ファーマシューティカルズ，インコーポレーテッド | 結合組織成長因子を標的とするｒｎａ複合体を用いた特発性肺胞線維症の治療 |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| EP3580339A4 (en) | 2017-02-10 | 2020-12-23 | Research & Business Foundation Sungkyunkwan University | LONG DOUBLE STRAND RNA FOR RNA INTERFERENCE |
| WO2023043239A1 (ko) * | 2021-09-15 | 2023-03-23 | 올릭스 주식회사 | 선천성 면역 반응 유도 효과를 갖는 이중가닥 rna 및 이의 용도 |
| WO2024186166A1 (ko) * | 2023-03-08 | 2024-09-12 | 올릭스 주식회사 | 선천성 면역 반응 유도 효과를 갖는 이중가닥 rna 및 이의 용도 |
| WO2026054553A1 (ko) * | 2024-09-06 | 2026-03-12 | 올릭스 주식회사 | 선천성 면역 반응 기반 항암 요법을 위한 이중 가닥 rna 및 이의 용도 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140249304A1 (en) | 2011-05-30 | 2014-09-04 | Research & Business Foundation Sungkyunkwan University | Long interfering dsrna simultaneously inducing an immune reaction and the inhibition of the expression of target genes |
| US20140288148A1 (en) | 2002-02-20 | 2014-09-25 | Sirna Therapeutics Inc | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
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| DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
| CA2429814C (en) | 2000-12-01 | 2014-02-18 | Thomas Tuschl | Rna interference mediating small rna molecules |
| US20050282188A1 (en) | 2001-05-18 | 2005-12-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
| US20080188430A1 (en) | 2001-05-18 | 2008-08-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA) |
| IL159756A0 (en) * | 2001-07-12 | 2004-06-20 | Univ Massachusetts | IN VIVO PRODUCTION OF SMALL INTERFERING RNAs THAT MEDIATE GENE SILENCING |
| US20050119202A1 (en) | 2001-10-26 | 2005-06-02 | Roland Kreutzer | Medicament to treat a fibrotic disease |
| US20040138163A1 (en) | 2002-05-29 | 2004-07-15 | Mcswiggen James | RNA interference mediated inhibition of vascular edothelial growth factor and vascular edothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| DE60310944T3 (de) | 2002-08-05 | 2017-08-03 | Silence Therapeutics Gmbh | Weitere neue formen von interferierende rns moleküle |
| WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| AU2003295600A1 (en) | 2002-11-14 | 2004-06-15 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
| CA2518475C (en) | 2003-03-07 | 2014-12-23 | Alnylam Pharmaceuticals, Inc. | Irna agents comprising asymmetrical modifications |
| US20040198640A1 (en) | 2003-04-02 | 2004-10-07 | Dharmacon, Inc. | Stabilized polynucleotides for use in RNA interference |
| US20050136437A1 (en) | 2003-08-25 | 2005-06-23 | Nastech Pharmaceutical Company Inc. | Nanoparticles for delivery of nucleic acids and stable double-stranded RNA |
| US8680063B2 (en) * | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
| US20100247540A1 (en) * | 2003-10-30 | 2010-09-30 | Chemocentryx, Inc. | Methods and Compositions For Modulating Angiogenesis |
| US20100145038A1 (en) * | 2003-11-24 | 2010-06-10 | Merck & Co., Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20060134787A1 (en) | 2004-12-22 | 2006-06-22 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA |
| WO2005062937A2 (en) | 2003-12-22 | 2005-07-14 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended sirna |
| US20060069050A1 (en) | 2004-02-17 | 2006-03-30 | University Of Massachusetts | Methods and compositions for mediating gene silencing |
| ES2423060T3 (es) | 2004-03-12 | 2013-09-17 | Alnylam Pharmaceuticals, Inc. | Agentes iRNA que tienen como diana al VEGF |
| KR101147147B1 (ko) | 2004-04-01 | 2012-05-25 | 머크 샤프 앤드 돔 코포레이션 | Ｒｎａ 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드 |
| AU2005247509C1 (en) * | 2004-05-27 | 2012-09-20 | Alnylam Pharmaceuticals, Inc. | Nuclease resistant double-stranded ribonucleic acid |
| WO2006031901A2 (en) | 2004-09-10 | 2006-03-23 | Somagenics, Inc. | SMALL INTERFERING RNAs THAT EFFICIENTLY INHIBIT VIRAL GENE EXPRESSION AND METHODS OF USE THEREOF |
| EP2377873B1 (en) | 2004-09-24 | 2014-08-20 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of ApoB and uses thereof |
| TWI386225B (zh) | 2004-12-23 | 2013-02-21 | Alcon Inc | 用於治療眼睛病症的結締組織生長因子（ＣＴＧＦ）ＲＮＡ干擾（ＲＮＡｉ）抑制技術 |
| US20060142228A1 (en) | 2004-12-23 | 2006-06-29 | Ambion, Inc. | Methods and compositions concerning siRNA's as mediators of RNA interference |
| AU2006235364A1 (en) | 2005-04-08 | 2006-10-19 | Marina Biotech, Inc. | RNAi therapeutic for respiratory virus infection |
| EP1891216B1 (en) | 2005-05-25 | 2012-02-22 | The University Of York | Hybrid interfering rna |
| CA2612047C (en) | 2005-06-24 | 2015-05-12 | Intervet International B.V. | Inactivated chimeric vaccines and related methods of use |
| PL2578685T3 (pl) * | 2005-08-23 | 2020-01-31 | The Trustees Of The University Of Pennsylvania | Rna zawierający zmodyfikowane nukleozydy i sposoby jego zastosowania |
| FR2890859B1 (fr) | 2005-09-21 | 2012-12-21 | Oreal | Oligonucleotide d'arn double brin inhibant l'expression de la tyrosinase |
| US7825099B2 (en) | 2006-01-20 | 2010-11-02 | Quark Pharmaceuticals, Inc. | Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes |
| WO2007089607A2 (en) | 2006-01-26 | 2007-08-09 | University Of Massachusetts | Rna silencing agents for use in therapy and nanotransporters for efficient delivery of same |
| PT1981902E (pt) | 2006-01-27 | 2015-11-02 | Biogen Ma Inc | Antagonistas dos recetores nogo |
| US20070218495A1 (en) | 2006-03-16 | 2007-09-20 | Dharmacon, Inc. | Methods, libraries and computer program products for gene silencing with reduced off-target effects |
| US7700541B2 (en) | 2006-04-06 | 2010-04-20 | Nitto Denko Corporation | Biodegradable cationic polymers |
| GB0608838D0 (en) | 2006-05-04 | 2006-06-14 | Novartis Ag | Organic compounds |
| US7915399B2 (en) * | 2006-06-09 | 2011-03-29 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
| EP2121924A1 (en) | 2007-03-02 | 2009-11-25 | MDRNA, Inc. | Nucleic acid compounds for inhibiting vegf family gene expression and uses thereof |
| US20100105134A1 (en) | 2007-03-02 | 2010-04-29 | Mdrna, Inc. | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| DK2164967T3 (en) | 2007-05-31 | 2015-10-19 | Univ Iowa Res Found | Reduction of off-target rna interferenstoksicitet |
| US20090004668A1 (en) | 2007-06-22 | 2009-01-01 | The Board Of Trustees Of The Leland Stanford Junior University | Pre-miRNA loop-modulated target regulation |
| CN107129957A (zh) * | 2007-06-29 | 2017-09-05 | 北京强新生物科技有限公司 | 促使长dsRNA可用于哺乳动物和其他所选动物细胞中的基因寻靶 |
| WO2009008645A2 (en) * | 2007-07-06 | 2009-01-15 | Mogam Biotechnology Research Institute | Linear double-stranded rna molecule interfering with different target genes |
| WO2009020344A2 (en) | 2007-08-06 | 2009-02-12 | Postech Acad Ind Found | Small interfering rnas (sirnas) controlling multiple target genes and method for preparing the same |
| EP3889261A1 (en) | 2007-08-27 | 2021-10-06 | 1Globe Health Institute LLC | Compositions of asymmetric interfering rna and uses thereof |
| EP2195428B1 (en) | 2007-09-19 | 2013-12-11 | Applied Biosystems, LLC | SiRNA SEQUENCE-INDEPENDENT MODIFICATION FORMATS FOR REDUCING OFF-TARGET PHENOTYPIC EFFECTS IN RNAi, AND STABILIZED FORMS THEREOF |
| RU2487716C2 (ru) | 2007-10-03 | 2013-07-20 | Кварк Фармасьютикалс, Инк. | Новые структуры малых интерферирующих рнк (sirna) |
| US8614311B2 (en) | 2007-12-12 | 2013-12-24 | Quark Pharmaceuticals, Inc. | RTP801L siRNA compounds and methods of use thereof |
| KR100949791B1 (ko) | 2007-12-18 | 2010-03-30 | 이동기 | 오프-타겟 효과를 최소화하고 ＲＮＡｉ 기구를 포화시키지않는 신규한 ｓｉＲＮＡ 구조 및 그 용도 |
| EP2257313A2 (en) | 2008-02-21 | 2010-12-08 | University of Kentucky Research Foundation | Ultra-small rnas as toll-like receptor-3 antagonists |
| US20110251258A1 (en) | 2008-07-24 | 2011-10-13 | Rxi Pharmaceuticals Corporation | Rnai constructs and uses thereof |
| WO2010026660A1 (ja) | 2008-09-08 | 2010-03-11 | 学校法人福岡大学 | Ｚｆａｔ遺伝子発現抑制ｒｎａ |
| EP2342340A1 (en) | 2008-09-22 | 2011-07-13 | Rxi Pharmaceuticals Corporation | Rna interference in skin indications |
| US20100227920A1 (en) | 2008-09-29 | 2010-09-09 | The Regents Of The University Of California | Aldehyde dehydrogenase inhibitors as novel depigmenting agents |
| US9745574B2 (en) | 2009-02-04 | 2017-08-29 | Rxi Pharmaceuticals Corporation | RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| WO2010094491A1 (en) | 2009-02-18 | 2010-08-26 | Silence Therapeutics Ag | Means for inhibiting the expression of ang2 |
| EP2408916A2 (en) | 2009-03-19 | 2012-01-25 | Merck Sharp&Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF CONNECTIVE TISSUE GROWTH FACTOR (CTGF) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| CN103555722B (zh) | 2009-04-03 | 2016-08-31 | 戴瑟纳制药公司 | 利用不对称双链rna特异性抑制kras的方法和组合物 |
| WO2011019887A2 (en) | 2009-08-14 | 2011-02-17 | Massachusetts Institute Of Technology | Waveguide coupler having continuous three-dimensional tapering |
| KR101207561B1 (ko) | 2009-12-15 | 2012-12-04 | 주식회사 코리아나화장품 | 티로시나제의 발현을 저해하는 ｓｉＲＮＡ 올리고뉴클레오타이드 및 이를 함유하는 화장료 조성물 |
| WO2011084193A1 (en) | 2010-01-07 | 2011-07-14 | Quark Pharmaceuticals, Inc. | Oligonucleotide compounds comprising non-nucleotide overhangs |
| CN103200945B (zh) | 2010-03-24 | 2016-07-06 | 雷克西制药公司 | 眼部症候中的rna干扰 |
| CA2834108A1 (en) | 2010-05-12 | 2011-11-17 | Val-Chum, Limited Partnership | Screening assays based on mag and/or abhd6 for selecting insulin secretion promoting agents |
| CA2812046A1 (en) | 2010-09-15 | 2012-03-22 | Alnylam Pharmaceuticals, Inc. | Modified irna agents |
| DK2631291T3 (da) | 2010-10-22 | 2019-06-11 | Olix Pharmaceuticals Inc | Nukleinsyremolekyler, der inducerer rna-interferens, og anvendelser deraf |
| AU2011338682B2 (en) | 2010-12-06 | 2017-04-27 | Quark Pharmaceuticals, Inc. | Double stranded oligonucleotide compounds comprising threose modifications |
| CA2828544A1 (en) | 2011-03-03 | 2012-09-07 | Quark Pharmaceuticals, Inc. | Oligonucleotide modulators of the toll-like receptor pathway |
| CN102719432B (zh) | 2011-03-29 | 2013-10-23 | 南京大学 | 特异性抑制肿瘤凋亡抑制基因Bcl2的双链不对称小核酸干扰分子asiRNA及其应用 |
| AU2012236099A1 (en) * | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
| AU2012284223B2 (en) | 2011-07-18 | 2017-06-22 | University Of Kentucky Research Foundation | Protection of cells from Alu-RNA-induced degenereation and inhibitors for protecting cells |
| US9707235B1 (en) | 2012-01-13 | 2017-07-18 | University Of Kentucky Research Foundation | Protection of cells from degeneration and treatment of geographic atrophy |
| KR101567576B1 (ko) | 2012-05-22 | 2015-11-10 | 올릭스 주식회사 | 세포 내 관통능을 가지고 ｒｎａ 간섭을 유도하는 핵산 분자 및 그 용도 |
| US9611473B2 (en) | 2012-09-12 | 2017-04-04 | Quark Pharmaceuticals, Inc. | Double-stranded nucleic acid compounds |
| CN110592082A (zh) | 2013-07-05 | 2019-12-20 | 柏业公司 | 呼吸疾病相关基因特异性siRNA、含有siRNA的双螺旋寡RNA结构及其用途 |
| EP3027223A1 (en) | 2013-07-31 | 2016-06-08 | QBI Enterprises Ltd. | Methods of use of sphingolipid polyalkylamine oligonucleotide compounds |
| US9790506B2 (en) | 2013-10-02 | 2017-10-17 | The Regents Of The University Of California | Diagnostic and screening methods for atopic dermatitis |
| US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
| US20170226507A1 (en) | 2014-05-05 | 2017-08-10 | The Brigham And Women's Hospital, Inc. | Coordinate control of pathogenic signaling by the mir-130/301 family in pulmonary hypertension and fibroproliferative diseases |
| US9139648B1 (en) | 2014-07-15 | 2015-09-22 | Kymab Limited | Precision medicine by targeting human NAV1.9 variants for treatment of pain |
| US20160319278A1 (en) | 2015-04-03 | 2016-11-03 | University Of Massachusetts | Fully stabilized asymmetric sirna |
| JP7027303B2 (ja) | 2015-07-27 | 2022-03-01 | オリックス ファーマシューティカルズ，インコーポレーテッド | メラニン産生を抑制するｒｎａ複合体 |
| JP7027311B2 (ja) | 2015-11-16 | 2022-03-01 | オリックス ファーマシューティカルズ，インコーポレーテッド | ＭｙＤ８８又はＴＬＲ３を標的とするＲＮＡ複合体を使用した加齢黄斑変性の治療 |
| CN108779464B (zh) | 2016-02-02 | 2022-05-17 | 奥利克斯医药有限公司 | 使用靶向angpt2和pdgfb的rna复合物治疗血管生成相关性疾病 |
| JP6944942B2 (ja) | 2016-02-02 | 2021-10-06 | オリックス ファーマシューティカルズ，インコーポレーテッド | ＩＬ４Ｒα、ＴＲＰＡ１、またはＦ２ＲＬ１を標的とするＲＮＡ複合体を用いたアトピー性皮膚炎および喘息の治療 |
| JP7049262B2 (ja) | 2016-04-11 | 2022-04-06 | オリックス ファーマシューティカルズ，インコーポレーテッド | 結合組織成長因子を標的とするｒｎａ複合体を用いた特発性肺胞線維症の治療 |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| EP3580339A4 (en) | 2017-02-10 | 2020-12-23 | Research & Business Foundation Sungkyunkwan University | LONG DOUBLE STRAND RNA FOR RNA INTERFERENCE |
-
2018
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- 2018-02-12 CN CN201880024222.3A patent/CN110770343A/zh active Pending
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- 2018-02-12 KR KR1020197025890A patent/KR20190108167A/ko not_active Ceased
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140288148A1 (en) | 2002-02-20 | 2014-09-25 | Sirna Therapeutics Inc | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20140249304A1 (en) | 2011-05-30 | 2014-09-04 | Research & Business Foundation Sungkyunkwan University | Long interfering dsrna simultaneously inducing an immune reaction and the inhibition of the expression of target genes |
Non-Patent Citations (3)
| Title |
|---|
| FEBS Letters，2014年，Vol.588，P.1037-1043 |
| nature biotechnology，2006年，Vol.24, No.5，P.559-565 |
| Ui-Tei K et al.，"RNAi induced in mammalian and Drosophila cells via transfection of dimers and trimers of small interfering RNA."，Journal of RNAi and gene silencing，2005年10月14日，Vol. 1, No. 2，p.79-87 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110770343A (zh) | 2020-02-07 |
| WO2018146557A3 (en) | 2018-10-25 |
| KR20190108167A (ko) | 2019-09-23 |
| WO2018146557A2 (en) | 2018-08-16 |
| JP2020508078A (ja) | 2020-03-19 |
| EP3580339A2 (en) | 2019-12-18 |
| EP3580339A4 (en) | 2020-12-23 |
| US20210285001A1 (en) | 2021-09-16 |
| US11591600B2 (en) | 2023-02-28 |
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