Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse

Several gene transfer methods, including viral or nonviral vehicles have be en developed, however, efficacy, safety or handling continue to present pro blems. We developed a nonviral and plasmid-based method for arterial gene t ransfer by in vivo electronic pulse, using a newly designed T-shaped electr ode. Using rabbit carotid arteries, we first optimized gene transfer effici ency, and firefly luciferase gene transfer via electronic pulse under 20 vo ltage (the pulse length: P-on time 20 ms, the pulse interval: P-off time 80 ms, number of pulse: 10 times) showed the highest gene expression. Exogeno us gene expression was detectable for at least up to 14 days, Electroporati on-mediated gene transfer of E coli lacZ with nuclear localizing signal rev ealed successful gene transfer to luminal endothelial cells and to medial c ells. Histological damage was recognized as the voltage was increased but n eointima formation 4 weeks after gene transfer was not induced. In vivo ele ctroporation-mediated arterial gene transfer is readily facilitated, is saf e and may prove to be an alternative form of gene transfer to the vasculatu re.