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Circulation. 1993 Dec;88(6):2838-48.

Efficient and selective adenovirus-mediated gene transfer into vascular neointima.

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  • 1National Heart, Lung, and Blood Institute, Cardiology Branch, Bethesda, MD 20892.

Abstract

BACKGROUND:

Previous attempts to target arterial smooth muscle cells (SMCs) for gene delivery using liposomal or retroviral methods were limited by low transfection efficiency. We therefore evaluated the efficiency of adenovirus-mediated gene delivery in cultured vascular SMCs and in an in vivo model of balloon injury-induced SMC cell proliferation.

METHODS AND RESULTS:

We used a recombinant adenovirus, Ad.RSV beta gal, which contained the beta-galactosidase (beta-gal) histochemical marker gene. For in vitro studies, rat aortic SMCs were incubated in media containing Ad.RSV beta gal for 5 to 120 minutes. The proportion of SMCs expressing the beta-gal gene product increased from 25% (5-minute exposure) to 80% (120-minute exposure). For in vivo studies, uninjured and injured rat carotid segments were incubated with 0.5 to 1.0 x 10(9) pfu Ad.RSV beta gal for 45 minutes. Uninjured arteries showed adenovirus-mediated gene transfer limited to the endothelium. Injured arteries were exposed to adenovirus 0, 3, 7, or 12 days after injury. In these segments, beta-gal expression was minimal with infection at 0 or 3 days after injury but marked when infection was delayed until 7 or 12 days after injury. Neointimal cells constituted the dominant target of adenovirus gene transfer, with efficiency of gene transfer ranging from 10% to > 75%. Medial SMCs, whether covered or uncovered by neointimal cells, were minimally infected. Infection with a control adenovirus vector showed no beta-gal staining.

CONCLUSIONS:

Recombinant adenovirus selectively targets neointimal cells with high-efficiency gene transfer. This suggests that adenovirus vectors should be useful in targeting cells for the delivery of genes whose products may be relevant to the treatment of restenosis.

PMID:
8252697
[PubMed - indexed for MEDLINE]
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