| Myocardial gene delivery using molecular cardiac surgery with recombinant adeno-associated virus vectors in vivo. | |
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MedLine Citation:
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PMID: 21228882 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We use a novel technique that allows for closed recirculation of vector genomes in the cardiac circulation using cardiopulmonary bypass, referred to here as molecular cardiac surgery with recirculating delivery (MCARD). We demonstrate that this platform technology is highly efficient in isolating the heart from the systemic circulation in vivo. Using MCARD, we compare the relative efficacy of single-stranded (ss) adeno-associated virus (AAV)6, ssAAV9 and self-complimentary (sc)AAV6-encoding enhanced green fluorescent protein, driven by the constitutive cytomegalovirus promoter to transduce the ovine myocardium in situ. MCARD allows for the unprecedented delivery of up to 48 green fluorescent protein genome copies per cell globally in the sheep left ventricular (LV) myocardium. We demonstrate that scAAV6-mediated MCARD delivery results in global, cardiac-specific LV gene expression in the ovine heart and provides for considerably more robust and cardiac-specific gene delivery than other available delivery techniques such as intramuscular injection or intracoronary injection; thus, representing a potential, clinically translatable platform for heart failure gene therapy.Gene Therapy advance online publication, 13 January 2011; doi:10.1038/gt.2010.168. |
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Authors:
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J D White; D M Thesier; J B D Swain; M G Katz; C Tomasulo; A Henderson; L Wang; C Yarnall; A Fargnoli; M Sumaroka; A Isidro; M Petrov; D Holt; R Nolen-Walston; W J Koch; H H Stedman; J Rabinowitz; C R Bridges |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-13 |
Journal Detail:
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Title: Gene therapy Volume: - ISSN: 1476-5462 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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