CN104540527A - Mir-15微小rna家族的抑制剂 - Google Patents
Mir-15微小rna家族的抑制剂 Download PDFInfo
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- CN104540527A CN104540527A CN201380039961.7A CN201380039961A CN104540527A CN 104540527 A CN104540527 A CN 104540527A CN 201380039961 A CN201380039961 A CN 201380039961A CN 104540527 A CN104540527 A CN 104540527A
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106692175A (zh) * | 2016-12-26 | 2017-05-24 | 大连医科大学附属第二医院 | miR‑665‑3p抑制物在制备防治缺血再灌注损伤药物中的应用 |
| CN113599540A (zh) * | 2021-05-27 | 2021-11-05 | 山西医科大学 | miRNA-195-5p在抑制或降低麦芽酚铝所致神经细胞损伤中的应用 |
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| CA2876180C (en) | 2012-06-21 | 2019-11-19 | MiRagen Therapeutics, Inc. | Oligonucleotide-based inhibitors comprising locked nucleic acid motif |
| EP2970968B1 (en) | 2013-03-15 | 2018-01-10 | Miragen Therapeutics, Inc. | Bridged bicyclic nucleosides |
| US10443044B2 (en) | 2014-04-17 | 2019-10-15 | Ips Heart | Generating cardiac progenitor cells from pluripotent stem cells using isoxazole or isoxazole like compounds |
| AR101449A1 (es) | 2014-08-04 | 2016-12-21 | Miragen Therapeutics Inc | Inhibidores de myh7b y usos de los mismos |
| JP2017523790A (ja) | 2014-08-07 | 2017-08-24 | レグルス セラピューティクス インコーポレイテッド | 代謝障害のためのマイクロｒｎａの標的化 |
| SG11201705907XA (en) | 2015-01-20 | 2017-08-30 | Miragen Therapeutics Inc | Mir-92 inhibitors and uses thereof |
| WO2017219170A1 (zh) * | 2016-06-19 | 2017-12-28 | 毛侃琅 | 特异抑制人 miRNA-29a 和 miR-424 表达的慢病毒载体的构建及其应用 |
| CN110177544A (zh) | 2016-11-29 | 2019-08-27 | 普尔泰克健康有限公司 | 用于递送治疗剂的外泌体 |
| US10941403B2 (en) | 2018-04-02 | 2021-03-09 | Oregon Health & Science University | Microrna inhibitors as anti-cancer therapeutics |
| JP7692829B2 (ja) | 2019-07-30 | 2025-06-16 | 塩野義製薬株式会社 | Ｍｕｒｆ１を標的とする核酸医薬 |
| EP4185694A1 (en) * | 2020-07-23 | 2023-05-31 | Johann Wolfgang Goethe-Universität Frankfurt | Combinatorial inhibition of mirnas for treatment of heart failure |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006069584A2 (en) * | 2004-12-29 | 2006-07-06 | Exiqon A/S | NOVEL OLIGONUCLEOTIDE COMPOSITIONS AND PROBE SEQUENCES USEFUL FOR DETECTION AND ANALYSIS OF microRNAs AND THEIR TARGET mRNAs |
| US20090053718A1 (en) * | 2005-03-23 | 2009-02-26 | Irena Naguibneva | NOVEL OLIGONUCLEOTIDE COMPOSITIONS AND PROBE SEQUENCES USEFUL FOR DETECTION AND ANALYSIS OF microRNAs AND THEIR TARGET mRNAs |
Family Cites Families (90)
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| PT1504126E (pt) | 2002-05-03 | 2014-06-02 | Univ Duke | Um método para regular a expressão génica |
| US7892793B2 (en) | 2002-11-04 | 2011-02-22 | University Of Massachusetts | Allele-specific RNA interference |
| CN102304570B (zh) | 2002-11-13 | 2015-01-21 | 托马斯杰斐逊大学 | 用于癌症诊断和治疗的组合物和方法 |
| CA2886504C (en) | 2002-12-20 | 2019-01-08 | Celera Corporation | Wdr12 polymorphisms associated with myocardial infarction, methods of detection and uses thereof |
| CN1768139A (zh) | 2003-02-10 | 2006-05-03 | 独立行政法人产业技术总合研究所 | 通过dna干扰调控基因的表达 |
| US8145436B2 (en) | 2003-07-15 | 2012-03-27 | The Trustees Of The University Of Pennsylvania | Method and systems for identifying micro-RNA targets and synthesizing novel micro-RNAs and uses of the same |
| EP1648914A4 (en) | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
| US8106180B2 (en) | 2003-08-07 | 2012-01-31 | Whitehead Institute For Biomedical Research | Methods and products for expression of micro RNAs |
| WO2005017145A1 (ja) | 2003-08-13 | 2005-02-24 | Japan Biological Informatics Consortium | 機能性ｒｎａが制御する被制御遺伝子の同定・予測方法及びその利用方法 |
| JPWO2005028648A1 (ja) | 2003-09-22 | 2007-11-15 | 愛知県 | リンパ腫の病型および予後診断方法 |
| CN1867680A (zh) | 2003-10-14 | 2006-11-22 | 诺瓦提斯公司 | 寡核苷酸微阵列 |
| US20050182011A1 (en) | 2003-11-13 | 2005-08-18 | Eric Olson | Inhibition of TRP channels as a treatment for cardiac hypertrophy and heart failure |
| EP1713916A4 (en) | 2003-12-15 | 2007-12-12 | College Medicine Pochon Cha Univ Ind Acad Coop Found | NEW, MIRNA MOLECULES ISOLATED FROM A HUMAN EMBRYONAL STEM CELL |
| CA2554818A1 (en) | 2004-02-09 | 2005-08-25 | Thomas Jefferson University | Diagnosis and treatment of cancers with microrna located in or near cancer-associated chromosomal features |
| WO2005078096A2 (en) | 2004-02-09 | 2005-08-25 | University Of Massachusetts | Dual functional oligonucleotides for use in repressing mutant gene expression |
| CA2556435C (en) | 2004-02-13 | 2014-08-12 | The Rockefeller University | Anti-microrna oligonucleotide molecules |
| US8088902B2 (en) | 2004-04-05 | 2012-01-03 | The Rockefeller University | DNA virus microRNA and methods for inhibiting same |
| US20050260648A1 (en) | 2004-04-06 | 2005-11-24 | Huffel Christophe V | Method for the determination of cellular transcriptional |
| US20060134639A1 (en) | 2004-04-06 | 2006-06-22 | Huffel Christophe V | Method for the determination of cellular transcriptional regulation |
| DK1735459T3 (da) | 2004-04-07 | 2012-05-29 | Exiqon As | Fremgangsmåder til kvantificering af microRNA'er og små interfererende RNA'er |
| EP2290070B1 (en) | 2004-05-28 | 2015-03-25 | Asuragen, Inc. | Methods and compositions involving microRNA |
| JP5192234B2 (ja) | 2004-08-10 | 2013-05-08 | 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 | 化学修飾オリゴヌクレオチド |
| JP2008511678A (ja) | 2004-09-02 | 2008-04-17 | イェール ユニバーシティ | マイクロｒｎａによるオンコジーンの調節 |
| FR2877350B1 (fr) | 2004-11-03 | 2010-08-27 | Centre Nat Rech Scient | IDENTIFICATION ET UTILISATION DE miRNAs IMPLIQUES DANS LA DIFFERENCIATION DE CELLULES ISSUES D'UNE LEUCEMIE MYELOIDE |
| ES2534302T3 (es) | 2004-11-12 | 2015-04-21 | Asuragen, Inc. | Procedimientos y composiciones que implican miARN y moléculas inhibidoras de miARN |
| US9550990B2 (en) | 2004-12-10 | 2017-01-24 | Ionis Pharmaceuticals, Inc. | Regulation of epigenetic control of gene expression |
| US20060185027A1 (en) | 2004-12-23 | 2006-08-17 | David Bartel | Systems and methods for identifying miRNA targets and for altering miRNA and target expression |
| WO2006071884A2 (en) | 2004-12-27 | 2006-07-06 | The Regents Of The University Of Michigan | Oligonucleotide based therapeutics |
| US8071306B2 (en) | 2005-01-25 | 2011-12-06 | Merck Sharp & Dohme Corp. | Methods for quantitating small RNA molecules |
| JP2006292367A (ja) | 2005-04-05 | 2006-10-26 | Mitsubishi Rayon Co Ltd | ｍｉＲＮＡ検出用マイクロアレイ |
| EP1877798A2 (en) | 2005-04-15 | 2008-01-16 | Cenix Bioscience GmbH | Human marker genes and agents for diagnosis, treatment and prophylaxis of cardiovascular disorders and artherosclerosis |
| CN101203611B (zh) | 2005-04-19 | 2013-08-14 | 巴斯福植物科学有限公司 | 控制基因表达的改良方法 |
| HUE027013T2 (en) | 2005-05-27 | 2016-10-28 | Ospedale San Raffaele Srl | A gene vector containing MI-RNA |
| US20070054287A1 (en) | 2005-05-31 | 2007-03-08 | Applera Corporation | Method for identifying medically important cell populations using micro rna as tissue specific biomarkers |
| US20070044164A1 (en) | 2005-05-31 | 2007-02-22 | Cold Spring Harbor Laboratory | Methods for producing microRNAs |
| US20090209621A1 (en) | 2005-06-03 | 2009-08-20 | The Johns Hopkins University | Compositions and methods for decreasing microrna expression for the treatment of neoplasia |
| US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
| WO2007021896A2 (en) | 2005-08-10 | 2007-02-22 | Alnylam Pharmaceuticals, Inc. | Chemically modified oligonucleotides for use in modulating micro rna and uses thereof |
| CN101426912A (zh) | 2005-08-17 | 2009-05-06 | 瑟纳治疗公司 | 介导rna干扰的化学修饰短干扰核酸分子 |
| CN101296702B (zh) | 2005-09-12 | 2012-11-28 | 俄亥俄州立大学研究基金会 | 用于诊断或治疗bcl2相关癌症的组合物和方法 |
| US20070092882A1 (en) | 2005-10-21 | 2007-04-26 | Hui Wang | Analysis of microRNA |
| WO2007056826A1 (en) | 2005-11-21 | 2007-05-24 | Johnson & Johnson Research Pty Limited | Multitargeting interfering rnas and methods of their use and design |
| US20070259827A1 (en) | 2006-01-25 | 2007-11-08 | University Of Massachusetts | Compositions and methods for enhancing discriminatory RNA interference |
| WO2007092181A2 (en) | 2006-01-26 | 2007-08-16 | Unversity Of Massachusetts | Compositions and methods for modulating translational repression |
| AU2007210034A1 (en) | 2006-01-26 | 2007-08-09 | University Of Massachusetts | RNA silencing agents for use in therapy and nanotransporters for efficient delivery of same |
| AU2007211082B2 (en) | 2006-01-27 | 2012-09-27 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for the use in modulation of microRNAs |
| US20100184209A1 (en) | 2006-02-17 | 2010-07-22 | Dharmacon, Inc. | Compositions and methods for inhibiting gene silencing by rna interference |
| EP1991706B1 (en) | 2006-03-02 | 2014-01-15 | The Ohio State University Research Foundation | Microrna expression profile associated with pancreatic cancer |
| CA3024953A1 (en) | 2006-04-03 | 2007-10-11 | Roche Innovation Center Copenhagen A/S | Pharmaceutical composition comprising anti-mirna antisense oligonucleotides |
| US20080220423A1 (en) | 2006-05-19 | 2008-09-11 | Soren Moller | Oligonucleotide probes useful for detection and analysis of microRNA precursors |
| WO2007147067A2 (en) | 2006-06-14 | 2007-12-21 | Rosetta Inpharmatics Llc | Methods and compositions for regulating cell cycle progression |
| US20090307788A1 (en) | 2006-06-19 | 2009-12-10 | Kobenhavns Universitet | Ribozyme mediated stabilization of polynucleotides |
| WO2008024499A2 (en) | 2006-08-25 | 2008-02-28 | Duke University | Methods for in vivo identification of endogenous mrna targets of micrornas |
| CA2663962A1 (en) | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention |
| US20090306181A1 (en) | 2006-09-29 | 2009-12-10 | Children's Medical Center Corporation | Compositions and methods for evaluating and treating heart failure |
| EP2476762B1 (de) | 2006-10-09 | 2014-01-08 | Julius-Maximilians-Universität Würzburg | MicroRNA (miRNA) zur Diagnose und Therapie von Herzerkrankungen |
| WO2008147430A2 (en) | 2006-10-11 | 2008-12-04 | Nucleonics, Inc. | Microrna-formatted multitarget interfering rna vector constructs and methods of using the same |
| US20100021914A1 (en) | 2006-11-23 | 2010-01-28 | Querdenker Aps | Oligonucleotides for modulating target rna activity |
| AU2007333110A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | miRNA regulated genes and pathways as targets for therapeutic intervention |
| AU2007333107A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | miR-21 regulated genes and pathways as targets for therapeutic intervention |
| AU2007333109A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Functions and targets of let-7 micro RNAs |
| WO2008073921A2 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mir-126 regulated genes and pathways as targets for therapeutic intervention |
| EP3536788A1 (en) | 2006-12-21 | 2019-09-11 | QIAGEN GmbH | Microrna target site blocking oligos and uses thereof |
| WO2008074328A2 (en) | 2006-12-21 | 2008-06-26 | Exiqon A/S | Microrna target site blocking oligos and uses thereof |
| CA2671270A1 (en) | 2006-12-29 | 2008-07-17 | Asuragen, Inc. | Mir-16 regulated genes and pathways as targets for therapeutic intervention |
| WO2008109373A1 (en) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting erbb gene expression and uses thereof |
| US9043994B2 (en) | 2007-03-13 | 2015-06-02 | Massachusetts Institute Of Technology | Cre-lox based gene knockdown constructs and methods of use thereof |
| WO2008116267A1 (en) | 2007-03-26 | 2008-10-02 | Crc For Asthma And Airways Ltd | Therapeutic targets and molecules |
| WO2008147839A1 (en) | 2007-05-23 | 2008-12-04 | Dharmacon, Inc. | Micro-rna scaffolds and non-naturally occurring micro-rnas |
| WO2009012263A2 (en) | 2007-07-18 | 2009-01-22 | The Trustees Of Columbia University In The City Of New York | Tissue-specific micrornas and compositions and uses thereof |
| AU2008275877B2 (en) | 2007-07-18 | 2015-01-22 | The Regents Of The University Of Colorado, A Body Corporate | Differential expression of microRNAs in nonfailing versus failing human hearts |
| US20090092980A1 (en) | 2007-07-20 | 2009-04-09 | Christoph Arenz | miRNA PROCESSING INHIBITOR EFFICACY ASSAYS AND SUBSTANCES |
| WO2009044895A1 (ja) | 2007-10-03 | 2009-04-09 | Kyowa Hakko Kirin Co., Ltd. | 標的遺伝子の発現を抑制する組成物 |
| KR101889518B1 (ko) | 2007-10-04 | 2018-08-17 | 로슈 이노베이션 센터 코펜하겐 에이/에스 | 마이크로ＭＩＲｓ |
| WO2009058913A2 (en) | 2007-10-29 | 2009-05-07 | University Of Massachusetts | Encapsulated nanoparticles for nucleic acid delivery |
| WO2009058818A2 (en) | 2007-10-29 | 2009-05-07 | The Board Of Regents Of The University Of Texas System | Compositions comprising a micro-rna and methods of their use in regulating cardiac remodeling |
| CN101951924B (zh) | 2007-11-09 | 2015-06-24 | 得克萨斯系统大学董事会 | Mir-15家族的微小rna调控心肌细胞存活和心脏修复 |
| US20100240058A1 (en) * | 2007-11-23 | 2010-09-23 | Panagene Inc. | MicroRNA Antisense PNAs, Compositions Comprising the Same, and Methods for Using and Evaluating the Same |
| WO2009109665A1 (en) | 2008-03-07 | 2009-09-11 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of microrna related diseases |
| EP2105145A1 (en) | 2008-03-27 | 2009-09-30 | ETH Zürich | Method for muscle-specific delivery lipid-conjugated oligonucleotides |
| EP2279267A4 (en) | 2008-03-27 | 2012-01-18 | Vascular Biosciences Inc | METHOD FOR IDENTIFYING NEW THERAPY CANDIDATES ON GENE EXPRESSION ANALYSIS IN DISEASES RELATED TO VACCINES |
| US20090326049A1 (en) | 2008-04-04 | 2009-12-31 | Alexander Aristarkhov | Blocking oligos for inhibition of microrna and sirna activity and uses thereof |
| US20100113284A1 (en) | 2008-04-04 | 2010-05-06 | Alexander Aristarkhov | Small interfering rna (sirna) target site blocking oligos and uses thereof |
| EP2990487A1 (en) | 2008-05-08 | 2016-03-02 | Asuragen, INC. | Compositions and methods related to mirna modulation of neovascularization or angiogenesis |
| AU2009256243A1 (en) | 2008-06-04 | 2009-12-10 | The Board Of Regents Of The University Of Texas System | Modulation of gene expression through endogenous small RNA targeting of gene promoters |
| WO2010036939A2 (en) | 2008-09-26 | 2010-04-01 | University Of Southern California | A system for synergistic expression of multiple small functional rna elements |
| EP2358398A2 (en) | 2008-10-24 | 2011-08-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
| WO2010126355A1 (en) | 2009-04-29 | 2010-11-04 | Academisch Medisch Centrum Bij De Universiteit Van Amsterdam | Means and methods for counteracting, preventing and/or determining heart failure, or a risk of heart failure |
| CN102803284B (zh) | 2009-06-08 | 2015-11-25 | 米拉根医疗公司 | 用于miRNA抑制剂和模拟物的化学修饰基序 |
-
2013
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- 2013-06-21 MX MX2014015641A patent/MX2014015641A/es unknown
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- 2013-06-21 CN CN201380039961.7A patent/CN104540527A/zh active Pending
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- 2013-06-21 MD MDA20150006A patent/MD20150006A2/ro not_active Application Discontinuation
- 2013-06-21 CA CA2876105A patent/CA2876105A1/en not_active Abandoned
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- 2013-06-21 KR KR1020157001535A patent/KR20150036140A/ko not_active Withdrawn
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- 2013-06-21 BR BR112014032239A patent/BR112014032239A2/pt not_active IP Right Cessation
- 2013-06-24 AR ARP130102219 patent/AR091539A1/es unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006069584A2 (en) * | 2004-12-29 | 2006-07-06 | Exiqon A/S | NOVEL OLIGONUCLEOTIDE COMPOSITIONS AND PROBE SEQUENCES USEFUL FOR DETECTION AND ANALYSIS OF microRNAs AND THEIR TARGET mRNAs |
| US20090053718A1 (en) * | 2005-03-23 | 2009-02-26 | Irena Naguibneva | NOVEL OLIGONUCLEOTIDE COMPOSITIONS AND PROBE SEQUENCES USEFUL FOR DETECTION AND ANALYSIS OF microRNAs AND THEIR TARGET mRNAs |
Non-Patent Citations (1)
| Title |
|---|
| THOMAS G. HULLINGER ET AL.: "Inhibition of miR-15 Protects Against Cardiac Ischemic Injury", 《CIRCULATION RESEARCH》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106692175A (zh) * | 2016-12-26 | 2017-05-24 | 大连医科大学附属第二医院 | miR‑665‑3p抑制物在制备防治缺血再灌注损伤药物中的应用 |
| CN113599540A (zh) * | 2021-05-27 | 2021-11-05 | 山西医科大学 | miRNA-195-5p在抑制或降低麦芽酚铝所致神经细胞损伤中的应用 |
| CN113599540B (zh) * | 2021-05-27 | 2023-05-23 | 山西医科大学 | miRNA-195-5p在制备抑制或降低麦芽酚铝所致神经细胞损伤的试剂中的应用 |
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| US9163235B2 (en) | 2015-10-20 |
| BR112014032239A2 (pt) | 2017-08-01 |
| MX2014015641A (es) | 2015-07-14 |
| SG11201408460UA (en) | 2015-01-29 |
| CA2876105A1 (en) | 2013-12-27 |
| IN2014DN10899A (enExample) | 2015-09-11 |
| HK1209621A1 (en) | 2016-04-08 |
| AU2013277033A1 (en) | 2015-01-22 |
| EA201590070A1 (ru) | 2015-04-30 |
| JP2015525081A (ja) | 2015-09-03 |
| MD20150006A2 (ro) | 2015-06-30 |
| EP2863956A4 (en) | 2016-01-20 |
| US20130345288A1 (en) | 2013-12-26 |
| WO2013192486A1 (en) | 2013-12-27 |
| KR20150036140A (ko) | 2015-04-07 |
| TW201406774A (zh) | 2014-02-16 |
| EP2863956A1 (en) | 2015-04-29 |
| AR091539A1 (es) | 2015-02-11 |
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