JP7425738B2 - 眼組織を標的とするウイルスベクター - Google Patents
眼組織を標的とするウイルスベクター Download PDFInfo
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- JP7425738B2 JP7425738B2 JP2020552312A JP2020552312A JP7425738B2 JP 7425738 B2 JP7425738 B2 JP 7425738B2 JP 2020552312 A JP2020552312 A JP 2020552312A JP 2020552312 A JP2020552312 A JP 2020552312A JP 7425738 B2 JP7425738 B2 JP 7425738B2
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| AU2019247748A1 (en) | 2018-04-03 | 2020-10-08 | Ginkgo Bioworks, Inc. | Antibody-evading virus vectors |
| EP3774852A1 (en) | 2018-04-03 | 2021-02-17 | Stridebio, Inc. | Antibody-evading virus vectors |
| MX2020010465A (es) | 2018-04-03 | 2021-01-08 | Vectores de virus para direccionamiento a tejidos oftalmicos. | |
| MA51353B1 (fr) * | 2018-04-05 | 2022-09-30 | Univ Sorbonne | Sérotype du virus adéno-associé recombinant hybride entre aav9 et aavrh74 possédant un tropisme hépatique réduit |
| AR118465A1 (es) | 2019-03-21 | 2021-10-06 | Stridebio Inc | Vectores de virus adenoasociados recombinantes |
| TW202102526A (zh) * | 2019-04-04 | 2021-01-16 | 美商銳進科斯生物股份有限公司 | 重組腺相關病毒及其用途 |
| US12611436B2 (en) | 2019-10-17 | 2026-04-28 | Sarepta Therapeutics, Inc. | AAV transfer cassette |
| JP2022551739A (ja) | 2019-10-17 | 2022-12-13 | ストライドバイオ，インコーポレイテッド | ニーマン・ピック病ｃ型の治療のためのアデノ随伴ウイルスベクター |
| TWI819268B (zh) * | 2020-01-16 | 2023-10-21 | 詹姆斯 Ｗ 希爾 | 藉由基因轉導改變眼睛顏色 |
| CA3177869A1 (en) * | 2020-05-05 | 2021-11-11 | Duke University | Cross-species compatible adeno-associated virus compositions and methods of use thereof |
| JP7842082B2 (ja) * | 2020-07-21 | 2026-04-07 | エフティージェン コーポレーション | 眼疾患を処置するための組成物および方法 |
| AU2021328475A1 (en) | 2020-08-19 | 2023-03-16 | Sarepta Therapeutics, Inc. | Adeno-associated virus vectors for treatment of Rett syndrome |
| TW202242124A (zh) | 2021-01-14 | 2022-11-01 | 美商史崔德生物公司 | 靶向ｔ細胞之ａａｖ載體 |
| KR20240095539A (ko) | 2021-10-08 | 2024-06-25 | 디노 테라퓨틱스, 인코포레이티드 | 캡시드 변이체 및 이의 사용 방법 |
| CN117801116A (zh) * | 2022-09-30 | 2024-04-02 | 上海玮美基因科技有限责任公司 | 一种融合型新型腺相关病毒及其应用 |
| WO2024124019A2 (en) | 2022-12-07 | 2024-06-13 | Ginkgo Bioworks, Inc. | Aav vectors targeting hematopoietic stem cells |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015038958A1 (en) | 2013-09-13 | 2015-03-19 | California Institute Of Technology | Selective recovery |
| WO2017201248A1 (en) | 2016-05-18 | 2017-11-23 | Voyager Therapeutics, Inc. | Modulatory polynucleotides |
| JP2018503376A (ja) | 2015-01-14 | 2018-02-08 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | 標的化遺伝子移入のための方法および組成物 |
Family Cites Families (250)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4039388A (en) | 1976-06-04 | 1977-08-02 | The United States Of America As Represented By The Government | Diagnostic test for Niemann-Pick disease |
| US4501729A (en) | 1982-12-13 | 1985-02-26 | Research Corporation | Aerosolized amiloride treatment of retained pulmonary secretions |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| AU7966987A (en) | 1986-09-08 | 1988-04-07 | Applied Biotechnology, Inc. | Empty viral capsid vaccines |
| US4968603A (en) | 1986-12-31 | 1990-11-06 | The Regents Of The University Of California | Determination of status in neoplastic disease |
| EP0442926A1 (en) | 1988-11-10 | 1991-08-28 | Imperial Cancer Research Technology Limited | Polypeptides |
| US5916563A (en) | 1988-11-14 | 1999-06-29 | United States Of America | Parvovirus protein presenting capsids |
| 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 |
| US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
| ES2026826A6 (es) | 1991-03-26 | 1992-05-01 | Ercros Sa | Procedimiento para la produccion de una vacuna subunidad contra el parvovirus canino y otros virus relacionados. |
| US5773278A (en) | 1991-05-03 | 1998-06-30 | Mount Sinai Medical Center | Acid sphingomyelinase gene |
| US5858784A (en) | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| WO1995013365A1 (en) | 1993-11-09 | 1995-05-18 | Targeted Genetics Corporation | Generation of high titers of recombinant aav vectors |
| US5869248A (en) | 1994-03-07 | 1999-02-09 | Yale University | Targeted cleavage of RNA using ribonuclease P targeting and cleavage sequences |
| ATE386131T1 (de) | 1994-04-13 | 2008-03-15 | Univ Rockefeller | Aav-vermittelte überbringung von dna in zellen des nervensystems |
| US6204059B1 (en) | 1994-06-30 | 2001-03-20 | University Of Pittsburgh | AAV capsid vehicles for molecular transfer |
| US5599706A (en) | 1994-09-23 | 1997-02-04 | Stinchcomb; Dan T. | Ribozymes targeted to apo(a) mRNA |
| US6040183A (en) | 1995-06-07 | 2000-03-21 | University Of North Carloina At Chapel Hill | Helper virus-free AAV production |
| US6093570A (en) | 1995-06-07 | 2000-07-25 | The University Of North Carolina At Chapel Hill | Helper virus-free AAV production |
| ATE452981T1 (de) | 1995-06-07 | 2010-01-15 | Univ North Carolina | Die transduktion von myoblasten mittels vektoren aus adenoassoziierten viren |
| ATE354957T1 (de) | 1995-12-15 | 2006-03-15 | Intronn Inc | Durch trans-spaltung erhaltene therapeutische molekule |
| US6083702A (en) | 1995-12-15 | 2000-07-04 | Intronn Holdings Llc | Methods and compositions for use in spliceosome mediated RNA trans-splicing |
| US5962313A (en) | 1996-01-18 | 1999-10-05 | Avigen, Inc. | Adeno-associated virus vectors comprising a gene encoding a lyosomal enzyme |
| WO1998011244A2 (en) | 1996-09-11 | 1998-03-19 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Aav4 vector and uses thereof |
| US6156303A (en) | 1997-06-11 | 2000-12-05 | University Of Washington | Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom |
| WO1999001555A1 (en) | 1997-07-03 | 1999-01-14 | The United States Of America Represented By The Secretary, Department Of Health And Human Services | Genes for niemann-pick type c disease |
| WO1999061601A2 (en) | 1998-05-28 | 1999-12-02 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Aav5 vector and uses thereof |
| US6984517B1 (en) | 1998-05-28 | 2006-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | AAV5 vector and uses thereof |
| US6562958B1 (en) | 1998-06-09 | 2003-05-13 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to Acinetobacter baumannii for diagnostics and therapeutics |
| US8299321B2 (en) | 1998-06-16 | 2012-10-30 | Monsanto Technology Llc | Nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
| US20100293663A2 (en) | 1998-06-16 | 2010-11-18 | Thomas La Rosa | Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
| US6544785B1 (en) | 1998-09-14 | 2003-04-08 | Mount Sinai School Of Medicine Of New York University | Helper-free rescue of recombinant negative strand RNA viruses |
| AU774706B2 (en) | 1998-09-22 | 2004-07-08 | Johns Hopkins University, The | Methods for large-scale production of recombinant AAV vectors |
| GB9822763D0 (en) | 1998-10-20 | 1998-12-16 | Univ Sheffield | Immunoglobin variant |
| ATE362542T1 (de) | 1998-11-05 | 2007-06-15 | Univ Pennsylvania | Nukleinsäuresequenzen des adeno-assoziierten virus des serotyps i, und vektoren und wirtszellen, die diese enthalten |
| US6759237B1 (en) | 1998-11-05 | 2004-07-06 | The Trustees Of The University Of Pennsylvania | Adeno-associated virus serotype 1 nucleic acid sequences, vectors and host cells containing same |
| AU780231B2 (en) | 1998-11-10 | 2005-03-10 | University Of North Carolina At Chapel Hill, The | Virus vectors and methods of making and administering the same |
| US6822071B1 (en) | 1998-11-12 | 2004-11-23 | The Regents Of The University Of California | Polypeptides from Chlamydia pneumoniae and their use in the diagnosis, prevention and treatment of disease |
| EP1887081A2 (en) | 1999-02-25 | 2008-02-13 | Ceres Incorporated | DNA Sequences |
| EP1033405A3 (en) | 1999-02-25 | 2001-08-01 | Ceres Incorporated | Sequence-determined DNA fragments and corresponding polypeptides encoded thereby |
| US20080229439A1 (en) | 1999-05-06 | 2008-09-18 | La Rosa Thomas J | Nucleic acid molecules and other molecules associated with transcription in plants and uses thereof for plant improvement |
| US20130326723A1 (en) | 1999-05-06 | 2013-12-05 | Thomas J. La Rosa | Soy nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
| US20040031072A1 (en) | 1999-05-06 | 2004-02-12 | La Rosa Thomas J. | Soy nucleic acid molecules and other molecules associated with transcription plants and uses thereof for plant improvement |
| US20110214206A1 (en) | 1999-05-06 | 2011-09-01 | La Rosa Thomas J | Nucleic acid molecules and other molecules associated with plants |
| US20090087878A9 (en) | 1999-05-06 | 2009-04-02 | La Rosa Thomas J | Nucleic acid molecules associated with plants |
| US20110093981A9 (en) | 1999-05-06 | 2011-04-21 | La Rosa Thomas J | Nucleic acid molecules and other molecules associated with transcription in plants and uses thereof for plant improvement |
| US6498244B1 (en) | 1999-05-28 | 2002-12-24 | Cell Genesys, Inc. | Adeno-associated virus capsid immunologic determinants |
| US7314912B1 (en) | 1999-06-21 | 2008-01-01 | Medigene Aktiengesellschaft | AAv scleroprotein, production and use thereof |
| DE19933288A1 (de) | 1999-07-15 | 2001-01-18 | Medigene Ag | Strukturprotein von Adeno-assoziiertem Virus mit veränderter Antigenität, seine Herstellung und Verwendung |
| CA2379166C (en) | 1999-08-09 | 2013-03-26 | Targeted Genetics Corporation | Enhancement of expression of a single-stranded, heterologous nucleotide sequence from recombinant viral vectors by designing the sequence such that it forms instrastrand base pairs |
| WO2001046226A2 (en) | 1999-12-22 | 2001-06-28 | Aventis Pasteur Limited | Chlamydia antigens and corresponding dna fragments and uses thereof |
| US6468524B1 (en) | 2000-03-22 | 2002-10-22 | The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | AAV4 vector and uses thereof |
| US20110131679A2 (en) | 2000-04-19 | 2011-06-02 | Thomas La Rosa | Rice Nucleic Acid Molecules and Other Molecules Associated with Plants and Uses Thereof for Plant Improvement |
| US20140130203A1 (en) | 2000-04-19 | 2014-05-08 | Thomas J. La Rosa | Rice nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
| JP2004520803A (ja) | 2000-04-21 | 2004-07-15 | コリクサ コーポレイション | 尋常性挫瘡の治療および診断のための組成物および方法 |
| ATE318923T1 (de) | 2000-06-01 | 2006-03-15 | Univ North Carolina | Doppelsträngige parvovirus-vektoren |
| US7201898B2 (en) | 2000-06-01 | 2007-04-10 | The University Of North Carolina At Chapel Hill | Methods and compounds for controlled release of recombinant parvovirus vectors |
| US7214786B2 (en) | 2000-12-14 | 2007-05-08 | Kovalic David K | Nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
| US7749492B2 (en) | 2001-01-05 | 2010-07-06 | Nationwide Children's Hospital, Inc. | AAV vectors and methods |
| WO2002053703A2 (en) | 2001-01-05 | 2002-07-11 | Children's Hospital, Inc. | Aav2 vectors and methods |
| AU2002256388A1 (en) | 2001-04-30 | 2002-11-11 | Cell Genesys, Inc. | Viral-mediated delivery and in vivo expression of polynucleotides encoding anti-angiogenic proteins |
| AU2002341541A1 (en) | 2001-06-22 | 2003-03-03 | Syngenta Participations Ag | Abiotic stress responsive polynucleotides and polypeptides |
| AU2002345250A1 (en) | 2001-06-22 | 2003-01-08 | Syngenta Participations Ag | Plant disease resistance genes |
| US6623729B2 (en) | 2001-07-09 | 2003-09-23 | Korea Advanced Institute Of Science And Technology | Process for preparing sustained release micelle employing conjugate of anticancer drug and biodegradable polymer |
| AU2001289843A1 (en) | 2001-08-28 | 2002-02-13 | Bayer Cropscience Ag | Polypeptides for identifying herbicidally active compounds |
| WO2003033515A1 (en) | 2001-10-15 | 2003-04-24 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of acne vulgaris |
| WO2003042361A2 (en) | 2001-11-09 | 2003-05-22 | Government Of The United States Of America, Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| MX359371B (es) | 2001-11-13 | 2018-09-25 | Univ Pennsylvania | Un metodo para detectar y/o identificar secuencias del virus adeno-asociado y aislamiento de secuencias novedosas identificadas de ese modo. |
| DK2573170T3 (en) | 2001-12-17 | 2018-04-09 | Univ Pennsylvania | Sequences of adeno-associated virus (AAV) serotype 9, vectors containing them, and their use |
| PT1453547T (pt) | 2001-12-17 | 2016-12-28 | Univ Pennsylvania | Sequências do vírus adeno-associado (aav) do serotipo 8, vetores contendo as mesmas, e utilizações destas |
| AU2003223766A1 (en) | 2002-04-30 | 2003-11-17 | University Of North Carolina At Chapel Hill | Secretion signal vectors |
| SI1496944T1 (sl) | 2002-05-01 | 2009-02-28 | Univ Florida | Izboljšani sistemi ekspresije RAAV za genetsko modifikacijo specifičnih kapsidnih proteinov |
| ITRM20020253A1 (it) | 2002-05-08 | 2003-11-10 | Univ Roma | Molecole chimeriche di snrna con sequenze antisenso per le giunzioni di splicing del gene della distrofina e applicazioni terapeutiche. |
| JP2005185101A (ja) | 2002-05-30 | 2005-07-14 | National Institute Of Agrobiological Sciences | 植物の全長ｃＤＮＡおよびその利用 |
| AU2003274397A1 (en) | 2002-06-05 | 2003-12-22 | University Of Florida | Production of pseudotyped recombinant aav virions |
| US7306913B2 (en) | 2002-12-20 | 2007-12-11 | Applera Corporation | Genetic polymorphisms associated with coronary stenosis, methods of detection and uses thereof |
| DK2270048T3 (en) | 2002-12-24 | 2016-01-18 | Rinat Neuroscience Corp | Anti-NGF antibodies and methods for their use |
| PT1633767T (pt) | 2003-06-02 | 2019-02-27 | Univ Massachusetts | Métodos e composições para controlar a eficácia do silenciamento de arn |
| SI1633772T1 (sl) | 2003-06-19 | 2016-06-30 | Genzyme Corporation | AAV virioni z zmanjšano imunoreaktivnostjo in uporaba za ta namen |
| US9441244B2 (en) | 2003-06-30 | 2016-09-13 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
| US7473531B1 (en) | 2003-08-08 | 2009-01-06 | Colora Corporation | Pancreatic cancer targets and uses thereof |
| US20060107345A1 (en) | 2003-09-30 | 2006-05-18 | Nickolai Alexandrov | Sequence-determined DNA fragments and corresponding polypeptides encoded thereby |
| EP2345731B1 (en) | 2003-09-30 | 2015-10-21 | The Trustees of the University of Pennsylvania | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof |
| EP3372614B1 (en) | 2004-04-07 | 2022-06-08 | Rinat Neuroscience Corp. | Methods for treating bone cancer pain by administering a nerve growth factor antagonist |
| US20060171926A1 (en) | 2004-04-30 | 2006-08-03 | Passini Marco A | Gene therapy for neurometabolic disorders |
| FR2874384B1 (fr) | 2004-08-17 | 2010-07-30 | Genethon | Vecteur viral adeno-associe pour realiser du saut d'exons dans un gene codant une proteine a domaines dispensables |
| JP4346526B2 (ja) | 2004-08-31 | 2009-10-21 | 株式会社東芝 | 半導体集積回路装置 |
| CN101056539B (zh) | 2004-09-09 | 2012-12-12 | 综合医院公司 | 调节心脏细胞中的磷酸酶活性 |
| JP5136766B2 (ja) | 2004-12-15 | 2013-02-06 | ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | キメラベクター |
| EP1839669A4 (en) | 2005-01-05 | 2012-12-12 | Shionogi & Co | NEW ANGIOGENESEHEMMER |
| WO2006092449A2 (en) | 2005-03-02 | 2006-09-08 | Metanomics Gmbh | Process for the production of fine chemicals |
| US20140199313A1 (en) | 2005-03-02 | 2014-07-17 | Metanomics Gmbh | Process for the Production of Fine Chemicals |
| WO2006119432A2 (en) | 2005-04-29 | 2006-11-09 | The Government Of The U.S.A., As Rep. By The Sec., Dept. Of Health & Human Services | Isolation, cloning and characterization of new adeno-associated virus (aav) serotypes |
| JP2008539698A (ja) | 2005-04-29 | 2008-11-20 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | 転写後レベルでの核酸発現調節のための方法および組成物 |
| EP2478760A1 (en) | 2005-05-10 | 2012-07-25 | Monsanto Technology LLC | Genes and uses for plant improvement |
| WO2007011682A2 (en) | 2005-07-15 | 2007-01-25 | Regents Of The University Of California | Methods and reagents for screening new drugs and for treating ion pump associated disorders and diseases |
| WO2007084773A2 (en) | 2006-01-20 | 2007-07-26 | University Of North Carolina At Chapel Hill | Enhanced production of infectious parvovirus vectors in insect cells |
| US7867484B2 (en) | 2006-01-27 | 2011-01-11 | University Of North Carolina At Chapel Hill | Heparin and heparan sulfate binding chimeric vectors |
| AR059371A1 (es) | 2006-02-08 | 2008-03-26 | Genzyme Corp | Terapia genica para la enfermedad de niemann-pick tipo a |
| CA2638913A1 (en) | 2006-02-10 | 2007-09-07 | The University Of Cincinnati | Phosphatase inhibitor protein-1 as a regulator of cardiac function |
| US7588772B2 (en) | 2006-03-30 | 2009-09-15 | Board Of Trustees Of The Leland Stamford Junior University | AAV capsid library and AAV capsid proteins |
| EP2018421B1 (en) | 2006-04-28 | 2012-12-19 | The Trustees of the University of Pennsylvania | Scalable production method for aav |
| WO2008027084A2 (en) | 2006-04-28 | 2008-03-06 | The Trustees Of The University Of Pennsylvania | Modified aav vectors having reduced capsid immunogenicity and use thereof |
| CN103849629B (zh) | 2006-06-21 | 2017-06-09 | 尤尼克尔Ip股份有限公司 | 具有经修饰的用于在昆虫细胞中产生aav的aav‑rep78翻译起始密码子的载体 |
| CN101711164B (zh) | 2007-01-18 | 2014-06-04 | 密苏里-哥伦比亚大学 | 可修复肌纤维膜中的神经元型一氧化氮合酶的合成小/微-抗肌萎缩蛋白基因 |
| US20120322861A1 (en) | 2007-02-23 | 2012-12-20 | Barry John Byrne | Compositions and Methods for Treating Diseases |
| US9611302B2 (en) | 2007-04-09 | 2017-04-04 | University Of Florida Research Foundation, Inc. | High-transduction-efficiency RAAV vectors, compositions, and methods of use |
| ES2714007T3 (es) | 2007-04-09 | 2019-05-24 | Univ Florida | Composiciones de vectores rAAV que tienen proteínas de la cápside modificadas en tirosina y métodos para su uso |
| US9725485B2 (en) * | 2012-05-15 | 2017-08-08 | University Of Florida Research Foundation, Inc. | AAV vectors with high transduction efficiency and uses thereof for gene therapy |
| AU2008300579B2 (en) | 2007-09-18 | 2014-11-13 | Basf Plant Science Gmbh | Plants with increased yield |
| EP2058401A1 (en) | 2007-10-05 | 2009-05-13 | Genethon | Widespread gene delivery to motor neurons using peripheral injection of AAV vectors |
| US10526627B2 (en) | 2007-11-30 | 2020-01-07 | Corn Products Development, Inc | Method for producing high molecular weight reduced viscosity starch pastes |
| BRPI0907786B1 (pt) | 2008-02-20 | 2021-06-01 | Ceres, Inc. | Método de produção de uma planta e método de aumentar o nível de tolerância a baixo teor de nitrogênio em uma planta |
| US20090221620A1 (en) | 2008-02-20 | 2009-09-03 | Celera Corporation | Gentic polymorphisms associated with stroke, methods of detection and uses thereof |
| WO2009108274A2 (en) | 2008-02-26 | 2009-09-03 | The University Of North Carolina At Chapel Hill | Methods and compositions for adeno-associated virus (aav) with hi loop mutations |
| WO2010011404A2 (en) | 2008-05-20 | 2010-01-28 | Eos Neuroscience, Inc. | Vectors for delivery of light-sensitive proteins and methods of use |
| JP2010002479A (ja) | 2008-06-18 | 2010-01-07 | Crossfor:Kk | メガネレンズ用装飾体およびメガネ用装飾体装着具 |
| US9415121B2 (en) | 2008-12-19 | 2016-08-16 | Nationwide Children's Hospital | Delivery of MECP2 polynucleotide using recombinant AAV9 |
| WO2010093784A2 (en) | 2009-02-11 | 2010-08-19 | The University Of North Carolina At Chapel Hill | Modified virus vectors and methods of making and using the same |
| WO2010114948A2 (en) | 2009-04-02 | 2010-10-07 | University Of Florida Research Foundation, Inc. | An inducible system for highly efficient production of recombinant adeno-associated virus (raav) vectors |
| HRP20250897T1 (hr) | 2009-05-02 | 2025-09-26 | Genzyme Corporation | Genska terapija za neurodegenerativne poremećaje |
| US8734809B2 (en) | 2009-05-28 | 2014-05-27 | University Of Massachusetts | AAV's and uses thereof |
| US20120252877A1 (en) | 2009-08-14 | 2012-10-04 | Theramind Research, Llc | Methods and compositions for treatment of tuberous sclerosis complex |
| EP2292781A1 (en) | 2009-08-17 | 2011-03-09 | Genethon | Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions |
| WO2011122950A1 (en) | 2010-04-01 | 2011-10-06 | Amsterdam Molecular Therapeutics (Amt) Ip B.V. | Monomeric duplex aav vectors |
| EP2561073B1 (en) | 2010-04-23 | 2016-08-24 | University of Massachusetts | Cns targeting aav vectors and methods of use thereof |
| US8927514B2 (en) | 2010-04-30 | 2015-01-06 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
| US9839696B2 (en) | 2010-04-30 | 2017-12-12 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
| US8628966B2 (en) | 2010-04-30 | 2014-01-14 | City Of Hope | CD34-derived recombinant adeno-associated vectors for stem cell transduction and systemic therapeutic gene transfer |
| WO2012057363A1 (ja) | 2010-10-27 | 2012-05-03 | 学校法人自治医科大学 | 神経系細胞への遺伝子導入のためのアデノ随伴ウイルスビリオン |
| EP2635111B1 (en) | 2010-11-05 | 2018-05-23 | The Board of Trustees of the Leland Stanford Junior University | Stabilized step function opsin proteins and methods of using the same |
| US10415056B2 (en) | 2010-11-10 | 2019-09-17 | Fred Hutchinson Cancer Research Center | Compositions and methods for generating adeno-associated viral vectors with undetectable capsid gene contamination |
| WO2012109570A1 (en) | 2011-02-10 | 2012-08-16 | The University Of North Carolina At Chapel Hill | Viral vectors with modified transduction profiles and methods of making and using the same |
| EP2675484B1 (en) | 2011-02-14 | 2018-05-30 | The Children's Hospital of Philadelphia | Improved aav8 vector with enhanced functional activity and methods of use thereof |
| CN105755044A (zh) * | 2011-04-22 | 2016-07-13 | 加利福尼亚大学董事会 | 具有变异衣壳的腺相关病毒病毒体及其使用方法 |
| WO2012159006A2 (en) | 2011-05-18 | 2012-11-22 | University Of Florida Research Foundation, Inc. | Polypeptides and vectors for targeting her2/neu expressing cells and uses thereof |
| CN107080847A (zh) | 2011-06-24 | 2017-08-22 | 森彻斯有限公司 | 细胞外靶向药物缀合物 |
| US9206425B2 (en) | 2011-07-28 | 2015-12-08 | Trustees Of Dartmouth College | Methods for treating Niemann-Pick type C disease |
| CA3177595A1 (en) | 2011-08-23 | 2013-02-28 | Evogene Ltd. | Isolated polynucleotides and polypeptides, and methods of using same for increasing plant yield and/or agricultural characteristics |
| HK1202434A1 (en) | 2011-11-22 | 2015-10-02 | The Children's Hospital Of Philadelphia | Virus vectors for highly efficient transgene delivery |
| FI124176B (en) | 2011-12-01 | 2014-04-15 | Helsingin Yliopisto | Polypeptide, polynucleotide, expression cassette, vector, host cell, plant and uses |
| US20140350087A9 (en) | 2012-03-22 | 2014-11-27 | Halozyme, Inc. | Oncovector Nucleic Acid Molecules and Methods of Use |
| WO2013143700A2 (en) | 2012-03-27 | 2013-10-03 | Curevac Gmbh | Artificial nucleic acid molecules comprising a 5'top utr |
| NZ701693A (en) | 2012-04-18 | 2017-02-24 | The Children’S Hospital Of Philadelphia | Composition and methods for highly efficient gene transfer using aav capsid variants |
| EP2660325A3 (en) | 2012-05-02 | 2014-02-12 | Christian Medical College | AAV vectors and corresponding nucleotide sequences and methods |
| WO2013170078A1 (en) | 2012-05-09 | 2013-11-14 | Oregon Health & Science University | Adeno associated virus plasmids and vectors |
| US10294281B2 (en) | 2012-05-15 | 2019-05-21 | University Of Florida Research Foundation, Incorporated | High-transduction-efficiency rAAV vectors, compositions, and methods of use |
| EP2492347A1 (en) | 2012-05-22 | 2012-08-29 | Laboratorios Del. Dr. Esteve, S.A. | Methods for the production of vectors |
| US20150182637A1 (en) | 2012-06-21 | 2015-07-02 | Association Institut De Myologie | Widespread gene delivery of gene therapy vectors |
| RU2679843C2 (ru) | 2012-07-06 | 2019-02-13 | Юниверсити Оф Айова Рисерч Фаундейшн | Векторные композиции с модифицированным аденоассоциированным вирусом |
| EP3196301B1 (en) | 2012-07-11 | 2018-10-17 | Sangamo Therapeutics, Inc. | Methods and compositions for the treatment of monogenic diseases |
| US9683268B2 (en) | 2012-09-19 | 2017-06-20 | Beth Israel Deaconess | Viruses associated with immunodeficiency and enteropathy and methods using same |
| JP5971661B2 (ja) | 2012-09-19 | 2016-08-17 | 国立大学法人 東京大学 | 神経活動依存的プロモータ活性を有するｄｎａ、及びこれを含むベクター |
| EP2900686B1 (en) | 2012-09-28 | 2020-06-10 | The University of North Carolina At Chapel Hill | Aav vectors targeted to oligodendrocytes |
| US9066966B2 (en) | 2013-02-01 | 2015-06-30 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Methods and pharmaceutical compositions for the treatment of cardiomyopathy due to friedreich ataxia |
| US9567376B2 (en) | 2013-02-08 | 2017-02-14 | The Trustees Of The University Of Pennsylvania | Enhanced AAV-mediated gene transfer for retinal therapies |
| US10266845B2 (en) | 2013-02-08 | 2019-04-23 | The Trustees Of The University Of Pennsylvania | Enhanced AAV-mediated gene transfer for retinal therapies |
| WO2014153083A1 (en) | 2013-03-14 | 2014-09-25 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Compositions and methods for predicting age of onset of a lysosomal storage disease or a disease associated with a lysosomal defect |
| ES2926774T3 (es) | 2013-03-15 | 2022-10-28 | Univ North Carolina Chapel Hill | Métodos y composiciones para vectores AAV de doble unión de glicano |
| EP3492597A3 (en) | 2013-05-21 | 2019-08-28 | University of Florida Research Foundation, Inc. | Capsid-modified, raav3 vector compositions and methods of use in gene therapy of human liver cancer |
| EP3003391B1 (en) | 2013-05-31 | 2021-09-22 | The Regents of The University of California | Adeno-associated virus variants and methods of use thereof |
| IL297919A (en) | 2013-07-22 | 2023-01-01 | Childrens Hospital Philadelphia | Variant aav and compositions, methods and uses for gene transfer to cells, organs and tissues |
| WO2015048534A1 (en) | 2013-09-26 | 2015-04-02 | University Of Florida Research Foundation, Inc. | Synthetic combinatorial aav capsid library for targeted gene therapy |
| US20160256571A1 (en) | 2013-09-30 | 2016-09-08 | Sanofi | Invention |
| CN106232618A (zh) | 2013-10-11 | 2016-12-14 | 马萨诸塞眼科耳科诊所 | 预测祖先病毒序列的方法及其用途 |
| GB201403684D0 (en) | 2014-03-03 | 2014-04-16 | King S College London | Vector |
| US10072251B2 (en) | 2014-02-19 | 2018-09-11 | University Of Massachusetts | Recombinant AAVS having useful transcytosis properties |
| US20170007720A1 (en) | 2014-02-21 | 2017-01-12 | University Of Florida Research Foundation, Inc. | Methods and compositions for gene delivery to on bipolar cells |
| EP3113787B1 (en) | 2014-03-04 | 2019-12-04 | University of Florida Research Foundation, Inc. | Improved raav vectors and methods for transduction of photoreceptors and rpe cells |
| WO2015164757A1 (en) | 2014-04-25 | 2015-10-29 | Oregon Health & Science University | Methods of viral neutralizing antibody epitope mapping |
| LT3137497T (lt) | 2014-05-02 | 2021-07-26 | Genzyme Corporation | Aav vektoriai, skirti tinklainės ir cns genų terapijai |
| BR112016027911A2 (pt) | 2014-05-28 | 2017-10-24 | Evogene Ltd | polinucleotídeos isolados, polipeptídeos e métodos de uso dos mesmos para aumento da tolerância ao estresse abiótico, biomassa e produção da planta |
| EP3151866B1 (en) | 2014-06-09 | 2023-03-08 | Voyager Therapeutics, Inc. | Chimeric capsids |
| HUE060907T2 (hu) | 2014-06-25 | 2023-04-28 | Acuitas Therapeutics Inc | Új lipidek és lipid nanorészecske formulációk nukleinsavak bevitelére |
| US9818383B2 (en) | 2014-07-28 | 2017-11-14 | University Of Connecticut | Methods and systems for non-destructive analysis of objects and production of replica objects |
| AU2015320694B2 (en) | 2014-09-24 | 2021-11-11 | City Of Hope | Adeno-associated virus vector variants for high efficiency genome editing and methods thereof |
| EP3200830B1 (en) | 2014-10-03 | 2020-09-09 | University of Massachusetts | High efficiency library-identified aav vectors |
| CN107073051B (zh) | 2014-10-21 | 2021-08-24 | 马萨诸塞大学 | 重组aav变体及其用途 |
| EP4344741A3 (en) | 2014-11-21 | 2024-08-28 | The University of North Carolina at Chapel Hill | Aav vectors targeted to the central nervous system |
| MX2017009336A (es) | 2015-01-16 | 2017-11-15 | Voyager Therapeutics Inc | Polinucleótidos dirigidos al sistema nervioso central. |
| US20180030096A1 (en) | 2015-02-03 | 2018-02-01 | University Of Florida Research Foundation, Inc. | Recombinant aav1, aav5, and aav6 capsid mutants and uses thereof |
| GB201502305D0 (en) | 2015-02-12 | 2015-04-01 | Hansa Medical Ab | Protein |
| GB201502306D0 (en) | 2015-02-12 | 2015-04-01 | Hansa Medical Ab | Protein |
| WO2016134338A1 (en) * | 2015-02-19 | 2016-08-25 | University Of Florida Research Foundation, Inc. | Recombinant aav vectors for gene therapy of human hematopoietic disorders |
| US11021519B2 (en) | 2015-03-02 | 2021-06-01 | Adverum Biotechnologies, Inc. | Compositions and methods for intravitreal delivery of polynucleotides to retinal cones |
| US11040113B2 (en) | 2015-03-23 | 2021-06-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical composition for the treatment and the prevention of neurological phenotype associated with Friedreich ataxia |
| JP6836999B2 (ja) | 2015-03-24 | 2021-03-03 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアＴｈｅ Ｒｅｇｅｎｔｓ Ｏｆ Ｔｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃａｌｉｆｏｒｎｉａ | アデノ随伴ウイルス変異体及びその使用方法 |
| US10081659B2 (en) | 2015-04-06 | 2018-09-25 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | Adeno-associated vectors for enhanced transduction and reduced immunogenicity |
| WO2016164642A1 (en) | 2015-04-08 | 2016-10-13 | The United States Of America, As Represented By The Secretary Of Health And Human Services | Viral gene therapy as treatment for cholesterol storage disease or disorder |
| EP3285788B1 (en) | 2015-04-23 | 2024-12-18 | University of Massachusetts | Modulation of aav vector transgene expression |
| US11046955B2 (en) | 2015-04-24 | 2021-06-29 | University Of Massachusetts | Modified AAV constructs and uses thereof |
| EP3294890A4 (en) | 2015-05-08 | 2018-10-03 | Children's Medical Research Institute | Promoters for expression of heterologous genes |
| GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
| GB201508026D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Capsid |
| JP6805174B2 (ja) | 2015-05-12 | 2020-12-23 | アメリカ合衆国 | 神経成長因子シグナルペプチド及び副甲状腺ホルモンを含むａａｖ分離株及び融合タンパク質 |
| WO2017015102A1 (en) | 2015-07-17 | 2017-01-26 | The Trustees Of The University Of Pennsylvania | Compositions and methods for achieving high levels of transduction in human liver cells |
| WO2017013648A1 (en) | 2015-07-19 | 2017-01-26 | Yeda Research And Development Co. Ltd. | SELECTIVE INHIBITORS OF Alpha2-CONTAINING ISOFORMS OF Na,K-ATPase AND USE THEREOF FOR REDUCTION OF INTRAOCULAR PRESSURE |
| WO2017019876A1 (en) | 2015-07-28 | 2017-02-02 | University Of Massachusetts | Transgenic expression of dnase i in vivo delivered by an adeno-associated virus vector |
| CN108603235A (zh) | 2015-07-30 | 2018-09-28 | 马萨诸塞眼科耳科诊所 | 祖先病毒序列及其用途 |
| ES2865487T3 (es) | 2015-09-28 | 2021-10-15 | Univ North Carolina Chapel Hill | Métodos y composiciones para vectores virales que evaden los anticuerpos |
| WO2017066764A2 (en) | 2015-10-16 | 2017-04-20 | William Marsh Rice University | Modification of n-terminal region of capsid proteins for enhanced properties of adeno-associated viruses |
| WO2017070516A1 (en) | 2015-10-22 | 2017-04-27 | University Of Massachusetts | Prostate-targeting adeno-associated virus serotype vectors |
| SG11201802408RA (en) | 2015-11-05 | 2018-05-30 | Bamboo Therapeutics Inc | Modified friedreich ataxia genes and vectors for gene therapy |
| EP3384015A4 (en) | 2015-12-01 | 2019-05-29 | Spark Therapeutics, Inc. | SCALABLE PROCESS FOR THE PREPARATION OF A RECOMBINANT ADENO ASSOCIATED VIRAL VECTOR IN A SERUM-FREE SUSPENSION CELL CULTURE SYSTEM SUITABLE FOR THE CLINICAL APPLICATION |
| EP3384034B1 (en) | 2015-12-02 | 2020-07-08 | The Board of Trustees of the Leland Stanford Junior University | Novel recombinant adeno-associated virus capsids with enhanced human skeletal muscle tropism |
| US10406244B2 (en) | 2015-12-02 | 2019-09-10 | The Board Of Trustees Of The Leland Stanford Junior University | AAV vectors with expanded packaging capacity |
| KR102423442B1 (ko) | 2015-12-11 | 2022-07-20 | 캘리포니아 인스티튜트 오브 테크놀로지 | 아데노-관련 바이러스를 지시하기 위한 타겟팅 펩타이드 |
| JP7406783B2 (ja) | 2015-12-14 | 2023-12-28 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | パルボウイルスベクターの高められた送達のための改変キャプシドタンパク質 |
| CA3012344A1 (en) | 2016-02-12 | 2017-08-17 | University Of Massachusetts | Anti-angiogenic mirna therapeutics for inhibiting corneal neovascularization |
| JP6947739B2 (ja) | 2016-02-16 | 2021-10-13 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 既存のヒト中和抗体に対して耐性である新規組換えアデノ随伴ウイルスカプシド |
| CA3011943A1 (en) | 2016-02-22 | 2017-08-31 | The University Of North Carolina At Chapel Hill | Aav-idua vector for treatment of mps i-associated blindness |
| SG11201808812RA (en) | 2016-04-15 | 2018-11-29 | Univ Pennsylvania | Novel aav8 mutant capsids and compositions containing same |
| US11866462B2 (en) | 2016-05-04 | 2024-01-09 | Oregon Health & Science University | Recombinant adeno-associated viral vectors |
| US11364308B2 (en) | 2016-05-13 | 2022-06-21 | 4D Molecular Therapeutics Inc. | Adeno-associated virus variant capsids and methods of use thereof |
| IL301963A (en) | 2016-07-21 | 2023-06-01 | Spark Therapeutics Inc | Scalable High Recovery Methods for High-Throughput Recombinant Adeno-Associated Viral Vector Production and Recombinant Adeno-Associated Viral Vectors Made So |
| IL305149A (en) | 2016-07-26 | 2023-10-01 | Biomarin Pharm Inc | Novel adeno-associated virus capsid proteins |
| US20190262373A1 (en) | 2016-08-16 | 2019-08-29 | The University Of North Carolina At Chapel Hill | Methods and compositions for targeted gene transfer |
| KR102451510B1 (ko) | 2016-09-08 | 2022-10-07 | 2세븐티 바이오, 인코포레이티드 | Pd-1 호밍 엔도뉴클레아제 변이체, 조성물 및 사용 방법 |
| EP3518985A4 (en) | 2016-09-29 | 2020-08-05 | University of Florida Research Foundation, Incorporated | AAVRH.10 VARIANTS WITH HOST ANTIBODY EXHAUST CAPACITIES AND MODIFIED TISSUE TARGETING PROPERTIES |
| CA3040179A1 (en) | 2016-10-19 | 2018-04-26 | Adverum Biotechnologies, Inc. | Modified aav capsids and uses thereof |
| WO2018119330A2 (en) | 2016-12-22 | 2018-06-28 | Oregon Health & Science University | Adeno associated viral vectors |
| US11905312B2 (en) | 2017-02-15 | 2024-02-20 | The University Of North Carolina At Chapel Hill | Methods and compositions for gene transfer across the vasculature |
| PT3589730T (pt) | 2017-02-28 | 2024-02-28 | Univ Pennsylvania | Vetor de vírus adenoassociado (aav) de clado f e suas utilizações |
| NZ756587A (en) | 2017-03-15 | 2025-12-19 | Univ North Carolina Chapel Hill | Polyploid adeno-associated virus vectors and methods of making and using the same |
| US10550405B2 (en) | 2017-03-15 | 2020-02-04 | The University Of North Carolina At Chapel Hill | Rational polyploid adeno-associated virus vectors and methods of making and using the same |
| WO2018204764A1 (en) | 2017-05-05 | 2018-11-08 | Camp4 Therapeutics Corporation | Identification and targeted modulation of gene signaling networks |
| CA3061968A1 (en) | 2017-05-10 | 2018-11-15 | Massachusetts Eye And Ear Infirmary | Methods and compositions for modifying assembly-activating protein (aap)-dependence of viruses |
| US11680275B2 (en) | 2017-06-06 | 2023-06-20 | University Of Massachusetts | Self-regulating AAV vectors for safe expression of MeCP2 in rett syndrome |
| CA3068010A1 (en) | 2017-06-20 | 2018-12-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Codon-optimized human npc1 genes for the treatment of niemann-pick type c1 deficiency and related conditions |
| EP3645021A4 (en) | 2017-06-30 | 2021-04-21 | Intima Bioscience, Inc. | ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY |
| US20210228738A1 (en) | 2017-07-17 | 2021-07-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions and methods for increasing or enhancing transduction of gene therapy vectors and for removing or reducing immunoglobulins |
| SG11202000840YA (en) | 2017-07-31 | 2020-02-27 | Reflection Biotechnologies Ltd | Cellular models of and therapies for ocular diseases |
| SI3740222T1 (sl) | 2018-01-17 | 2023-11-30 | Meiragtx Uk Ii Limited | Modificiran kapsidni protein raav za gensko terapijo |
| IL276859B2 (en) | 2018-02-27 | 2025-12-01 | Univ Pennsylvania | Novel adeno-associated virus (aav) vectors, aav vectors having reduced capsid deamidation and uses therefor |
| EP3759218A4 (en) | 2018-02-28 | 2021-12-08 | The University of North Carolina at Chapel Hill | PROCEDURES AND COMPOSITIONS FOR ANTIBODY ELIMINATING VIRUS VECTORS |
| EP3762500A1 (en) | 2018-03-06 | 2021-01-13 | Voyager Therapeutics, Inc. | Insect cell manufactured partial self-complementary aav genomes |
| CA3092871A1 (en) | 2018-03-06 | 2019-09-12 | University Of Florida Research Foundation, Incorporated | Aav chimeras |
| EP3765624A4 (en) | 2018-03-16 | 2022-05-25 | Research Institute at Nationwide Children's Hospital | Increasing tissue specific gene delivery by capsid modification |
| EP3774852A1 (en) | 2018-04-03 | 2021-02-17 | Stridebio, Inc. | Antibody-evading virus vectors |
| AU2019247748A1 (en) | 2018-04-03 | 2020-10-08 | Ginkgo Bioworks, Inc. | Antibody-evading virus vectors |
| MX2020010465A (es) | 2018-04-03 | 2021-01-08 | Vectores de virus para direccionamiento a tejidos oftalmicos. | |
| US20210214749A1 (en) | 2018-05-16 | 2021-07-15 | Voyager Therapeutics, Inc. | Directed evolution |
| WO2020106916A1 (en) | 2018-11-21 | 2020-05-28 | Stridebio, Inc. | Recombinant viral vectors and nucleic acids for producing the same |
| DK3906066T5 (da) | 2019-01-04 | 2024-08-05 | Ultragenyx Pharmaceutical Inc | Geneterapikonstruktioner til behandling af wilsons sygdom |
| AR118465A1 (es) | 2019-03-21 | 2021-10-06 | Stridebio Inc | Vectores de virus adenoasociados recombinantes |
| CA3140049A1 (en) | 2019-05-14 | 2020-11-19 | Duke University | Compositions and methods for the treatment of atpase-mediated diseases |
| US12611436B2 (en) | 2019-10-17 | 2026-04-28 | Sarepta Therapeutics, Inc. | AAV transfer cassette |
| JP2022551739A (ja) | 2019-10-17 | 2022-12-13 | ストライドバイオ，インコーポレイテッド | ニーマン・ピック病ｃ型の治療のためのアデノ随伴ウイルスベクター |
| AU2021328475A1 (en) | 2020-08-19 | 2023-03-16 | Sarepta Therapeutics, Inc. | Adeno-associated virus vectors for treatment of Rett syndrome |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015038958A1 (en) | 2013-09-13 | 2015-03-19 | California Institute Of Technology | Selective recovery |
| JP2018503376A (ja) | 2015-01-14 | 2018-02-08 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | 標的化遺伝子移入のための方法および組成物 |
| WO2017201248A1 (en) | 2016-05-18 | 2017-11-23 | Voyager Therapeutics, Inc. | Modulatory polynucleotides |
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