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In vivo gene transfer into rat arterial walls with novel adeno-associated virus vectors.

Abstract：

PURPOSE:We studied the ability of recombinant adeno-associated virus (rAAV) vectors to achieve gene transfer in vivo to intact rat carotid arteries. METHODS:Isolated segments of uninjured rat carotid arteries were incubated with (1) rAAV vectors that expressed a beta-galactosidase gene, (2) a related vector with no promoter, or (3) a normal saline solution. Gene transfer was evaluated with in situ polymerase chain reaction (PCR). Transgene expression was assessed at intervals that ranged from 24 hours to 2 months by measurement of beta-galactosidase activity and protein mass in tissue extracts with fluorometric and enzyme-linked immunosorbent assays, respectively. Dose dependence of expression was determined for virus concentrations that ranged from 5 x 10(4) to 5 x 10(5) infectious units (iu)/ml. RESULTS:Light microscopic analysis of in situ PCR-stained histologic sections of transduced vessel walls showed approximately 90% of intimal and medial cell nuclei contained the beta-galactosidase gene, compared with none in control arteries. In vivo beta-galactosidase expression was (1) highest 24 hours after gene transfer, (2) elevated for 1 month, and (3) dose responsive. CONCLUSIONS:rAAV vectors can mediate focal gene transfer into the intact rat carotid artery with detectable levels of transgene expression for 1 month and are potentially useful agents for in vivo gene transfer into intact arteries.

journal_name

J Vasc Surg

journal_title

Journal of vascular surgery

authors

Arnold TE,Gnatenko D,Bahou WF

doi

10.1016/s0741-5214(97)70357-4

subject

Has Abstract

pub_date

1997-02-01 00:00:00

pages

347-55

issue

2

eissn

0741-5214

issn

1097-6809

pii

A78288

journal_volume

25

pub_type

杂志文章

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