High-efficiency endovascular gene delivery via therapeutic ultrasound

OBJECTIVES We studied enhancement of local gene delivery to the arterial wall by using an endovascular catheter ultrasound (US). BACKGROUND Ultrasound exposure is standard for enhancement of in vitro gene delivery. We postulate that in vivo endovascular applications can be safely developed. METHODS We used a rabbit model of arterial mechanical overdilation injury. After arterial overdilation, US catheters were introduced in bilateral rabbit femoral arteries and perfused with plasmid or adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm(2), 16 min), and the contralateral artery did not. RESULTS Relative to controls, US exposure enhanced BFP expression measured via fluorescence 12-fold for plasmid (1,502.1 +/- 927.3 vs. 18,053.9 +/- 11,612 mum(2), p < 0.05) and 19-fold for adenovirus (877.1 +/- 577.7 vs. 17,213.15 +/- 3,892 <mu>m(2), p < 0.05) while increasing cell death for the adenovirus group only (26 +/- 5.78% vs. 13 +/- 2.55%, p < 0.012). CONCLUSIONS Endovascular US enhanced vascular gene delivery and increased the efficiency of nonviral platforms to levels previously attained only by adenoviral strategies. (J Am Coll Cardiol 2001; 37:1975-80) (C) 2001 by the American College of Cardiology.