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.