High-efficiency endovascular gene delivery via therapeutic ultrasound.
OBJECTIVE
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.
Amabile
P G
PG
Department of Cardiovascular and Interventional Radiology, Stanford University Medical Center, California 94305, USA.
Waugh
J M
JM
Lewis
T N
TN
Elkins
C J
CJ
Janas
W
W
Dake
M D
MD
D017546:Angioscopy; D000818:Animals; D001158:Arteries; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D011817:Rabbits; D018084:Ultrasonography, Interventional