High-efficiency endovascular gene delivery via therapeutic ultrasound

Abstract

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 plasmidor adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm2, 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 microm2, p < 0.05) and 19-fold for adenovirus (877.1+/-577.7 vs. 17,213.15+/-3,892 microm2, 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.