Adeno-associated virus vector transduction of vascular smooth muscle cellsin vivo

Citation
M. Richter et al., Adeno-associated virus vector transduction of vascular smooth muscle cellsin vivo, PHYSIOL GEN, 2(3), 2000, pp. 117-127
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
PHYSIOLOGICAL GENOMICS
ISSN journal
1094-8341 → ACNP
Volume
2
Issue
3
Year of publication
2000
Pages
117 - 127
Database
ISI
SICI code
1094-8341(20000427)2:3<117:AVVTOV>2.0.ZU;2-2
Abstract
Adeno-associated virus (AAV) vectors might offer solutions for restenosis a nd angiogenesis by transducing nondividing cells and providing long-term ge ne expression. We investigated the feasibility of vascular cell transductio n by AAV vectors in an in vivo rabbit carotid artery model. Time course of gene expression, inflammatory reaction to the vector, and effects of varyin g viral titer, exposure time, and intraluminal pressures on gene expression were examined. Recombinant AAV vectors with an Rous sarcoma virus promoter and alkaline phosphatase reporter gene were injected intraluminally into t ransiently isolated carotid segments. Following transduction, gene expressi on increased significantly over 14 days and then remained stable to 28 days , the last time point examined. Medial vascular smooth muscle cells were th e main cell type transduced even with an intact endothelial layer. Increasi ng the viral titer and intraluminal pressure both enhanced transduction eff iciency to achieve a mean of 34 +/- 7% of the subintimal layer of smooth mu scle cells expressing gene product. A mild inflammatory reaction, composed of T cells with only rare macrophages, with minimal intimal thickening was demonstrated in 40% of transduced vessels; inflammatory cells were not dete cted in sham-operated control arteries. These findings demonstrate that AAV is a promising vector for intravascular applications in coronary and perip heral vascular diseases.