EXPERIMENTAL STUDY
High-efficiency endovascular gene delivery via therapeutic ultrasound
Philippe G. Amabile, MD*,
Jacob M. Waugh, MD*,
Thomas N. Lewis, PhD ,
Christopher J. Elkins, PhD*,
Wolfgang Janas, RVT and
Michael D. Dake, MD*
* Department of Cardiovascular and Interventional Radiology, Stanford University Medical Center, Stanford, California, USA
EKOS Corporation, Bothell, Washington, USA
Manuscript received October 3, 2000;
revised manuscript received February 9, 2001,
accepted February 19, 2001.
Reprint requests and correspondence: Dr. Michael D. Dake, Department of Cardiovascular and Interventional Radiology, Stanford University Medical Center, Room H-3647, Stanford, California 94305
mddake{at}stanford.edu
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/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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Abbreviations and Acronyms
| | Adv | = adenovirus | | BFP | = blue fluorescent protein | | CMV | = cytomegalovirus | | DNA | = deoxyribonucleic acid | | p | = plasmid | | PBS | = phosphate buffered saline | | US | = ultrasound |
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