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A comparison of intravenous and indirect intracoronary delivery of AAV5, AAV6 and AAV9 for cardiac gene transfer in mice


Cardiac gene transfer is a potentially useful treatment for patients with heart disease. The adeno-associated virus (AAV) is a frequently used vector in preclinical gene transfer, but the optimal AAV serotype and route of delivery has not been established. I examined the relative efficacy of three AAV serotypes (AAV5, AAV6, AAV9) and two vector delivery methods (indirect intracoronary, intravenous) to determine the combination that would provide the highest level of cardiac transgene expression in mice. Using enhanced green fluorescent protein (EGFP) as a reporter to quantify transgene expression, AAV5.EGFP, AAV6.EGFP, and AAV9.EGFP [5 x 10¹¹ genome copies (gc)] were delivered via indirect intracoronary or intravenous injection. Three weeks later hearts were removed and EGFP expression was quantified using fluorescent microscopy and immunoblotting. AAV DNA copy number was measured by quantitative PCR. Within each serotype, indirect intracoronary delivery was superior to intravenous delivery. Indirect intracoronary delivery of AAV9 provided the highest level of cardiac gene expression. This vector and delivery method should be used in preclinical studies in which a high level of transgene expression is required

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