Document Detail


Myocardial gene delivery using molecular cardiac surgery with recombinant adeno-associated virus vectors in vivo.
MedLine Citation:
PMID:  21228882     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-13
Journal Detail:
Title:  Gene therapy     Volume:  18     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-09     Completed Date:  2011-10-07     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  546-52     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiac Surgical Procedures / methods*
Cardiopulmonary Bypass
Cytomegalovirus
Dependovirus / genetics*
Gene Transfer Techniques*
Genetic Therapy / methods*
Genetic Vectors*
Green Fluorescent Proteins / genetics
Myocardium* / metabolism
Sheep
Grant Support
ID/Acronym/Agency:
1-R01-HL083078-01A2/HL/NHLBI NIH HHS; P30-DK047757/DK/NIDDK NIH HHS; R01 HL083078/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
147336-22-9/Green Fluorescent Proteins
Comments/Corrections

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