GENE TRANSFER APPROACHES TO ATRIAL FIBRILATION

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DESCRIPTION (provided by applicant): Post-operative atrial fibrillation (post-op AF) is the most common compication of cardiac surgery. Post-op AF increases morbidity and mortality after surgery, including increased stay in the ICU and hospital, and increased risks of stroke, congestive heart failure and death. The impact on public health is substantial. Adding to the problems caused by post-op AF is the inadequacy of preventive therapies. We propose gene therapy as a new strategy to treat post-op AF. We have efficacy data in a pig model of post-op AF that shows prevention of sustained AF for 2 weeks after atrial gene transfer of AdKCNH2-G628S, a time that coincides with the window of risk for post-op AF. Here, we propose formal preclinical testing of AdKCNH2- G628S with the following specific aim: To successfully complete formal preclinical biodistribution and toxicology testing under Good Laboratory Practice (GLP)-certified conditions using Good Manufacturing Practice (GMP)-certified materials. Successful completion of this aim will complete the necessary preclinical testing before moving this idea to clinical trial.