TY - JOUR
T1 - High-efficiency endovascular gene delivery via therapeutic ultrasound
AU - Amabile, Philippe G.
AU - Waugh, Jacob M.
AU - Lewis, Thomas N.
AU - Elkins, Christopher J.
AU - Janas, Wolfgang
AU - Dake, Michael D.
N1 - Funding Information: This work was funded through departmental sources and a grant from the EKOS Corporation.
PY - 2001/6/1
Y1 - 2001/6/1
N2 - 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 μm2, p < 0.05) and 19-fold for adenovirus (877.1 ± 577.7 vs. 17,213.15 ± 3,892 μm2, 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.
AB - 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 μm2, p < 0.05) and 19-fold for adenovirus (877.1 ± 577.7 vs. 17,213.15 ± 3,892 μm2, 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.
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U2 - 10.1016/S0735-1097(01)01253-0
DO - 10.1016/S0735-1097(01)01253-0
M3 - Article
C2 - 11401141
SN - 0735-1097
VL - 37
SP - 1975
EP - 1980
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 7
ER -