High-efficiency endovascular gene delivery via therapeutic ultrasound

Philippe G. Amabile, Jacob M. Waugh, Thomas N. Lewis, Christopher J. Elkins, Wolfgang Janas, Michael D. Dake

Research output: Contribution to journalArticle

68 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1975-1980
Number of pages6
JournalJournal of the American College of Cardiology
Volume37
Issue number7
DOIs
StatePublished - Jun 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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