Document Detail


Cardiac gene delivery using DNA-adenoviral constructs.
MedLine Citation:
PMID:  16010010     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In view of the limitations of current cardiac gene transfer techniques by direct myocardial injection, or via the coronary vasculature, we have been attempting to develop potentially clinically applicable methods. Selective catheterization of the coronary arteries has been performed, but the duration of exposure of the heart to the virus is limited. Present systems require high infusion pressure to inject the virus, which could result in endothelial or myocardial injury, and extracardiac transgene expression occurs. An alternative method has been developed in which the adenoviral vector is administered following cardioplegic arrest of the heart during cardiopulmonary bypass (CPB), which allows prolonged myocardial contact with the adenoviral vector. This may be advantageous since intracoronary delivery of vector in a Langendorff perfused heart model has shown that prolonged contact time with the virus improves gene transfer. Despite the detrimental effect of cold temperatures and contact with blood on transgene expression in the in vitro and ex vivo studies, we have demonstrated that these factors are unimportant in this in vivo model. Exposure of extracardiac tissues to the vector is limited. Moreover, administration of the beta2AR transgene has resulted in amelioration of impaired cardiac function following CPB and cardioplegic arrest.
Authors:
J Mark Jones; Walter J Koch
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Methods in molecular medicine     Volume:  112     ISSN:  1543-1894     ISO Abbreviation:  Methods Mol. Med.     Publication Date:  2005  
Date Detail:
Created Date:  2005-07-12     Completed Date:  2005-08-04     Revised Date:  2006-04-21    
Medline Journal Info:
Nlm Unique ID:  101123138     Medline TA:  Methods Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  49-57     Citation Subset:  IM    
Affiliation:
Department of Cardiac Surgery, Royal Victoria Hospital, Belfast, UK.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Cardiopulmonary Bypass / methods
DNA, Complementary
Disease Models, Animal
Gene Expression
Gene Transfer Techniques*
Genetic Vectors*
Heart / virology
Chemical
Reg. No./Substance:
0/DNA, Complementary

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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