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        Gene Delivery to the Mammalian Heart Using AAV Vectors

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        There are a large number of cardiovascular diseases that could be treated by myocardial gene transfer (1 ,2 ). These include congestive heart failure, ischemic heart disease, and cardiomyopathy. In addition to its potential for treatment of disease, myocardial gene transfer is useful for the analysis of gene expression and promoter function and for generating animal models of human disease such as pulmonary hypertension. The ideal vector for myocardial gene therapy should give efficient and stable transduction of cardiomyocytes in vivo. Recombinant adenovirus vectors have been used to transduce cardiomyocytes in rodents, rabbits, pigs, and humans by both intramyocardial injection and intracoronary infusion (3 5 ). Although efficient transduction can be obtained with adenovirus vectors, immune responses and elimination of transduced cells results in only transient expression in immunocompetent hosts. Vectors based on recombinant adeno-associated virus (rAAV) offer a number of attractive features and are emerging as promising gene transfer vehicles for many in vivo applications.
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