High-efficiency endovascular gene delivery via therapeutic ultrasound

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American College of Cardiology 2001-06, Vol.37 (7), p.1975-1980
Main Authors: Amabile, Philippe G, Waugh, Jacob M, Lewis, Thomas N, Elkins, Christopher J, Janas, Wolfgang, Dake, Michael D
Format: Article
Language:English
Subjects:
Angioscopy
Animals
Arteries
Biological and medical sciences
Diseases of the cardiovascular system
Genetic Therapy - methods
Male
Medical sciences
Rabbits
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Ultrasonography, Interventional
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(01)01253-0