Microbubble-enhanced ultrasound for vascular gene delivery

Progress in cardiovascular gene therapy has been hampered by concerns over the safety and practicality of viral vectors and the inefficiency of curren t nonviral transfection techniques. We have previously reported that ultras ound exposure (USE) enhances transgene expression in vascular cells by up t o 10-fold after naked DNA transfection, and enhances lipofection by up to t hree-fold. We report here that performing USE in the presence of microbubbl e echocontrast agents enhances acoustic cavitation and is associated with a pproximately 300-fold increments in transgene expression after naked DNA tr ansfections. This approach also enhances by four-fold the efficiency of pol yplex transfection, yielding transgene expression levels approximately 3000 -fold higher than after naked DNA alone. These data indicate an important r ole for acoustic cavitation in the effects of USE. Ultrasound can be focuse d upon almost any organ and hence this approach holds promise as a means to deliver targeted gene therapy in cardiovascular conditions such as such an gioplasty restenosis and in many other clinical situations.