AU2013221615B2 - Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions - Google Patents

Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions Download PDF

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AU2013221615B2
AU2013221615B2 AU2013221615A AU2013221615A AU2013221615B2 AU 2013221615 B2 AU2013221615 B2 AU 2013221615B2 AU 2013221615 A AU2013221615 A AU 2013221615A AU 2013221615 A AU2013221615 A AU 2013221615A AU 2013221615 B2 AU2013221615 B2 AU 2013221615B2
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vector
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pct
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AU2013221615A1 (en
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Mei Hua Gao
H. Kirk Hammond
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University of California San Diego UCSD
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University of California Berkeley
University of California San Diego UCSD
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AU2013221615A 2012-02-14 2013-02-13 Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions Active AU2013221615B2 (en)

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Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8734809B2 (en) 2009-05-28 2014-05-27 University Of Massachusetts AAV's and uses thereof
EP2814513B1 (en) * 2012-02-14 2017-12-20 The Regents of The University of California Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions
AU2015242354A1 (en) * 2014-04-03 2016-11-10 The Regents Of The University Of California Systemic delivery of virus vectors encoding urocortin-2 and related genes to treat diabetes-related cardiac dysfunction and congestive heart failure
WO2015191508A1 (en) 2014-06-09 2015-12-17 Voyager Therapeutics, Inc. Chimeric capsids
RU2020140209A (ru) 2014-10-21 2021-01-25 Юниверсити Оф Массачусетс Варианты рекомбинантных aav и их применения
CN107106689A (zh) 2014-11-05 2017-08-29 沃雅戈治疗公司 用于治疗帕金森病的aadc多核苷酸
MX2017006216A (es) 2014-11-14 2018-08-29 Voyager Therapeutics Inc Composiciones y métodos para tratar la esclerosis lateral amiotrófica (ela).
KR102584655B1 (ko) 2014-11-14 2023-10-06 보이저 테라퓨틱스, 인크. 조절성 폴리뉴클레오티드
US11697825B2 (en) 2014-12-12 2023-07-11 Voyager Therapeutics, Inc. Compositions and methods for the production of scAAV
CN114621318A (zh) * 2015-05-12 2022-06-14 加利福尼亚大学董事会 用于炎症和纤维化的肽治疗
HK1250623A1 (zh) * 2015-05-28 2019-01-11 Cornell University 腺相关病毒介导的c1ei递送作为用於血管性水肿的疗法
US11326182B2 (en) 2016-04-29 2022-05-10 Voyager Therapeutics, Inc. Compositions for the treatment of disease
WO2017189964A2 (en) 2016-04-29 2017-11-02 Voyager Therapeutics, Inc. Compositions for the treatment of disease
RU2758488C2 (ru) 2016-05-18 2021-10-28 Вояджер Терапьютикс, Инк. Модулирующие полинуклеотиды
AU2017268382B2 (en) 2016-05-18 2023-09-28 Voyager Therapeutics, Inc. Compositions and methods of treating Huntington's disease
JP2019531787A (ja) 2016-08-30 2019-11-07 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 生物医学的ターゲティング及びデリバリーの方法並びにそれを実行するための装置及びシステム
AU2017341849B2 (en) 2016-10-13 2024-03-21 University Of Massachusetts AAV capsid designs
BR112019015081A2 (pt) * 2017-01-23 2020-03-10 Rutgers, The State University Of New Jersey Composições para reduzir a expressão da sarcolipina e prevenir e tratar a distrofia muscular e a cardiomiopatia e os métodos de utilização
CN110573612B (zh) * 2017-02-28 2024-11-01 基因药物株式会社 含肿瘤特异性溶瘤腺病毒和免疫检查点抑制剂的抗癌组合物
WO2018204803A1 (en) 2017-05-05 2018-11-08 Voyager Therapeutics, Inc. Compositions and methods of treating huntington's disease
AU2018261790B2 (en) 2017-05-05 2024-10-03 Voyager Therapeutics, Inc. Compositions and methods of treating amyotrophic lateral sclerosis (ALS)
JOP20190269A1 (ar) 2017-06-15 2019-11-20 Voyager Therapeutics Inc بولي نوكليوتيدات aadc لعلاج مرض باركنسون
CN111132626B (zh) 2017-07-17 2024-01-30 沃雅戈治疗公司 轨迹阵列引导系统
US11760987B2 (en) 2017-09-07 2023-09-19 The Regents Of The University Of California Compositions and methods for the treatment or prevention of heart failure
EP3687582A4 (en) 2017-09-29 2021-07-14 Voyager Therapeutics, Inc. RESCUE OF CENTRAL AND PERIPHERAL NEUROLOGICAL PHENOTYPE OF FRIEDREICH ATAXIA BY INTRAVENOUS ADMINISTRATION
US11434502B2 (en) 2017-10-16 2022-09-06 Voyager Therapeutics, Inc. Treatment of amyotrophic lateral sclerosis (ALS)
EP4454654A3 (en) 2017-10-16 2025-02-19 Voyager Therapeutics, Inc. Treatment of amyotrophic lateral sclerosis (als)
MX2020012077A (es) 2018-05-15 2021-03-09 Voyager Therapeutics Inc Composiciones y metodos para el tratamiento de la enfermedad de parkinson.
CN112367971A (zh) * 2018-06-11 2021-02-12 加利福尼亚大学董事会 用以治疗眼睛疾病的脱甲基化
SG11202103151RA (en) 2018-09-28 2021-04-29 Voyager Therapeutics Inc Frataxin expression constructs having engineered promoters and methods of use thereof
US20220305066A1 (en) * 2020-06-12 2022-09-29 Gencellmed Inc. Recombinant herpes simplex virus for multiple targeting and use thereof
CN112826823B (zh) * 2021-01-11 2022-03-08 中国人民解放军军事科学院军事医学研究院 多西环素在制备治疗和/或预防和/或缓解和/或改善心肌病药物中的应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214797B1 (en) * 1995-06-13 2001-04-10 The Salk Institute For Biological Studies Urocortin peptides, nucleic acid encoding same methods for using same
WO2001034208A1 (en) * 1999-11-05 2001-05-17 The Regents Of The University Of California Techniques and compositions for treating cardiovascular disease by in vivo gene delivery
WO2002012307A1 (en) * 2000-08-04 2002-02-14 Research Development Foundation Urocortin proteins and uses thereof
WO2003062277A1 (en) * 2002-01-16 2003-07-31 The Procter & Gamble Company Corticotropin releasing factor receptor 2 agonists
NZ523803A (en) * 2000-08-04 2004-08-27 Res Dev Foundation Human urocortin-related polypeptide (URP) and uses thereof to rreat a pathophysiological state, eg stress, anxiety and appetite dysfunction
WO2006086402A2 (en) * 2005-02-08 2006-08-17 Research Development Foundation Compositions and methods related to soluble g-protein coupled receptors(sgpcrs)
WO2006121532A2 (en) * 2005-03-31 2006-11-16 Mytogen, Inc. Treatment for heart disease
WO2009065080A1 (en) * 2007-11-16 2009-05-22 San Diego State University Research Foundation Compositions and method for manipulating pim-1 activity in circulatory system cells

Family Cites Families (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US5217879A (en) 1989-01-12 1993-06-08 Washington University Infectious Sindbis virus vectors
US5733542A (en) 1990-11-16 1998-03-31 Haynesworth; Stephen E. Enhancing bone marrow engraftment using MSCS
US5270192A (en) 1991-02-07 1993-12-14 Monsanto Company Biological artificial liver
US5846743A (en) 1995-02-22 1998-12-08 Brigham And Women's Hospital, Inc. Polyphoshoinositide binding peptides for intracellular drug delivery
US7361332B2 (en) 1995-03-17 2008-04-22 The Regents Of The University Of California Treating tumors using implants comprising combinations of allogeneic cells
WO1997016533A1 (en) 1995-10-31 1997-05-09 The Regents Of The University Of California Mammalian artificial chromosomes and methods of using same
EP1704878B1 (en) 1995-12-18 2013-04-10 AngioDevice International GmbH Crosslinked polymer compositions and methods for their use
US6025155A (en) 1996-04-10 2000-02-15 Chromos Molecular Systems, Inc. Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes
US6933331B2 (en) 1998-05-22 2005-08-23 Nanoproducts Corporation Nanotechnology for drug delivery, contrast agents and biomedical implants
US5874268A (en) 1996-09-23 1999-02-23 Duke University Method of introducing exogenous compounds into cells by electroporation and apparatus for same
ES2235227T3 (es) * 1996-11-01 2005-07-01 Ark Therapeutics Limited Utilizacion de vegf para la preparacion de un medicamento destinado al tratamiento o prevencion de la hiperplasia intimal y dispositivo para su administracion.
US6630137B1 (en) 1997-04-28 2003-10-07 Eli Lilly And Company Activated protein C formulations
EP0980428A2 (en) * 1997-05-06 2000-02-23 The Regents Of The University Of California TECHNIQUES AND COMPOSITIONS FOR TREATING HEART FAILURE AND VENTRICULAR REMODELING BY $i(IN VIVO) DELIVERY OF ANGIOGENIC TRANSGENES
US20050095227A1 (en) * 1997-07-22 2005-05-05 The General Hospital Corporation Treating heart failure
SE9704076D0 (sv) 1997-11-06 1997-11-06 Holdingbolaget Vid Goeteborgs Method for permeabilisation of cell structures and use thereof
US6886568B2 (en) 1998-04-08 2005-05-03 The Johns Hopkins University Method for fabricating cell-containing implants
ES2313784T3 (es) * 1998-05-28 2009-03-01 The Government Of The Usa, As Represented By The Secretary, Department Of Health And Human Services Vector aav5 y usos del mismo.
US6589503B1 (en) 1998-06-20 2003-07-08 Washington University Membrane-permeant peptide complexes for medical imaging, diagnostics, and pharmaceutical therapy
US6958212B1 (en) 1999-02-01 2005-10-25 Eidgenossische Technische Hochschule Zurich Conjugate addition reactions for the controlled delivery of pharmaceutically active compounds
AU2460001A (en) * 1999-12-27 2001-07-09 Regents Of The University Of California, The Gene therapy for congestive heart failure
EP1604024A4 (en) 2000-04-06 2008-04-23 Wayne P Franco METHODS OF USING GROWTH FACTORS FOR TREATING CARDIOPATHY
US7442390B2 (en) 2000-06-05 2008-10-28 University Of South Florida Method for enhancing engraftment of cells using mesenchymal progenitor cells
EP1559777A1 (en) 2001-04-24 2005-08-03 Hokkaido Technology Licensing Office Co., Ltd. Process for maturating small heptocyte-rich colonies into liver tissue
ES2602352T3 (es) * 2001-12-17 2017-02-20 The Trustees Of The University Of Pennsylvania Secuencias de serotipo 8 de virus adenoasociado (VAA), vectores que las contienen y usos de las mismas
US7166133B2 (en) 2002-06-13 2007-01-23 Kensey Nash Corporation Devices and methods for treating defects in the tissue of a living being
US20040151766A1 (en) 2003-01-30 2004-08-05 Monahan Sean D. Protein and peptide delivery to mammalian cells in vitro
US7241455B2 (en) 2003-04-08 2007-07-10 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing radiation-crosslinked polymer for controlled delivery of a therapeutic agent
JP4708342B2 (ja) 2003-07-25 2011-06-22 デックスコム・インコーポレーテッド 埋設可能な装置に用いる酸素増大膜システム
US7794706B2 (en) 2003-10-14 2010-09-14 Medivas, Llc Bioactive wound dressings and implantable devices and methods of use
WO2005063156A1 (en) 2003-12-22 2005-07-14 Shear/Kershman Laboratories, Inc. Oral peptide delivery system with improved bioavailability
US20070077286A1 (en) 2003-12-24 2007-04-05 Tsutomu Ishihara Drug-containing nanoparticle, process for producing the same and parenterally administered preparation from the nanoparticle
US20050244463A1 (en) 2004-04-30 2005-11-03 Allergan, Inc. Sustained release intraocular implants and methods for treating ocular vasculopathies
US8658203B2 (en) 2004-05-03 2014-02-25 Merrimack Pharmaceuticals, Inc. Liposomes useful for drug delivery to the brain
WO2006014035A1 (en) 2004-08-06 2006-02-09 Biospectrum, Inc. Multiple layered liposome and preparation method thereof
US7442389B2 (en) 2004-08-20 2008-10-28 Artes Medical, Inc. Methods of administering microparticles combined with autologous body components
EP1796693A2 (en) 2004-08-26 2007-06-20 Chandrashekhar P. Pathak Implantable tissue compositions and method
US7351423B2 (en) 2004-09-01 2008-04-01 Depuy Spine, Inc. Musculo-skeletal implant having a bioactive gradient
US7501486B2 (en) 2004-09-07 2009-03-10 Burnham Institute For Medical Research Peptides that selectively home to heart vasculature and related conjugates and methods
EP1812074B1 (en) 2004-10-18 2010-12-29 Nitto Denko Corporation Intracellular peptide delivery
US7759120B2 (en) 2005-03-02 2010-07-20 Kps Bay Medical, Inc. Seeding implantable medical devices with cells
JP5639338B2 (ja) 2005-07-27 2014-12-10 プロチバ バイオセラピューティクス インコーポレイティッド リポソームの製造システムおよび製造方法
US20070265221A1 (en) * 2006-05-09 2007-11-15 Weiss Robert G Methods to improve creatine kinase metabolism and contractile function in cardiac muscle for the treatment of heart failure
US7982018B2 (en) * 2006-10-16 2011-07-19 Conjuchem, Llc Modified corticotropin releasing factor peptides and uses thereof
CA2580907A1 (en) 2006-11-21 2008-05-21 The Bionic Ear Institute Choroid plexus cell implantation to prevent and/or treat hearing loss
CA2711179A1 (en) 2007-12-31 2009-07-16 Nanocor Therapeutics, Inc. Rna interference for the treatment of heart failure
CN104815319A (zh) * 2008-05-16 2015-08-05 科尔泰拉公司 治疗慢性心力衰竭的方法
CA2724540C (en) * 2008-05-16 2014-07-08 Corthera, Inc. Treating dyspnea associated with acute heart failure with relaxin
CA2742710A1 (en) * 2008-11-04 2010-05-14 Janssen Pharmaceutica Nv Crhr2 peptide agonists and uses thereof
US8734809B2 (en) * 2009-05-28 2014-05-27 University Of Massachusetts AAV's and uses thereof
BR112012010661A2 (pt) * 2009-11-04 2016-11-22 Janssen Pharmaceutica Nv método para tratar insuficiência cardíaca com peptídeos semelhantes à estressecopina
EP2814513B1 (en) * 2012-02-14 2017-12-20 The Regents of The University of California Systemic delivery and regulated expression of paracrine genes for cardiovascular diseases and other conditions
PT3405215T (pt) * 2016-01-19 2022-09-20 Univ California Métodos para o tratamento da doença de danon e outros transtornos da autofagia

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214797B1 (en) * 1995-06-13 2001-04-10 The Salk Institute For Biological Studies Urocortin peptides, nucleic acid encoding same methods for using same
WO2001034208A1 (en) * 1999-11-05 2001-05-17 The Regents Of The University Of California Techniques and compositions for treating cardiovascular disease by in vivo gene delivery
WO2002012307A1 (en) * 2000-08-04 2002-02-14 Research Development Foundation Urocortin proteins and uses thereof
NZ523803A (en) * 2000-08-04 2004-08-27 Res Dev Foundation Human urocortin-related polypeptide (URP) and uses thereof to rreat a pathophysiological state, eg stress, anxiety and appetite dysfunction
WO2003062277A1 (en) * 2002-01-16 2003-07-31 The Procter & Gamble Company Corticotropin releasing factor receptor 2 agonists
WO2006086402A2 (en) * 2005-02-08 2006-08-17 Research Development Foundation Compositions and methods related to soluble g-protein coupled receptors(sgpcrs)
WO2006121532A2 (en) * 2005-03-31 2006-11-16 Mytogen, Inc. Treatment for heart disease
WO2009065080A1 (en) * 2007-11-16 2009-05-22 San Diego State University Research Foundation Compositions and method for manipulating pim-1 activity in circulatory system cells

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
GAFFNEY, MM et al. 'Cardiovascular gene therapy: current status and therapeutic potential' British Journal of Pharmacology, 2007, vol. 152, pages 175-188 *
Lai, N.C. et al. 'Intravenous Delivery of AAV9 encoding urocortin 2 increases cardiac function in normal mice' Conference on Experimental Biology. Anaheim, CA, USA. April 24-28 2010. The FASEB Journal, 2012, vol. 26 issue1_supplement *
Lyon, AR et al. 'Gene therapy: targeting the myocardium' Heart, 2008, vol. 94, pages 89-99 *
M. PEPE ET AL, "Intramyocardial VEGF-B167 Gene Delivery Delays the Progression Towards Congestive Failure in Dogs With Pacing-Induced Dilated Cardiomyopathy", CIRCULATION RESEARCH, 2010, vol. 106, no. 12, pages 1893 - 1903 *
MEILI-BUTZ SILVIA ET AL, "Chronic Administration of Urocortin 2 in Hypertension-Induced Hypertrophy: Effects on Intracellular Calcium Handling and Hemodynamics", DATABASE BIOSIS, Database accession no. PREV201000180016, *

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