The research and development of genetic delivery for treatment of ischemic heart disease is the focus of many investigations. However current techniques of gene delivery are inefficient and very limited in scope. The objective of the proposed studies is to develop a biodegradable polymer-based DNA delivery system for sustained release of vascular endothelial growth factor (VEGF) to promote revascularization in ischemic myocardium. Specifically, the applicant proposes to: encapsulate DNA in small nanometer diameter particles with a poly-lactic-polyglycolic acid co-polymer, assess the in vitro delivery mechanism of nanoparticles using beta -galactosidase as a model reporter gene, and then finally to evaluate the efficacy of VEGF gene transfer in a rat cardiac injection model. These experiments may help establish the feasibility of using this delivery system for gene therapy.
