In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors

P. Lemarchand, M. Jones, I. Yamada, R. G. Crystal

Research output: Contribution to journalArticle

237 Citations (Scopus)

Abstract

Replication-deficient recombinant adenovirus vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in the endothelium. To evaluate the feasibility of adenovirus-mediated gene transfer in vivo in normal intact blood vessels, adenovirus vectors containing the Escherichia coli lacZ gene or a human α1-antitrypsin (α1AT) cDNA were injected in vivo into the lumen of an occluded vessel segment of sheep jugular vein and/or carotid artery. After 15 minutes of incubation, circulation was restored; the vessels were harvested 1-28 days later and evaluated for gene transfer and expression. Three days after in vivo exposure to the lacZ adenovirus vector, the endothelium of jugular veins and carotid arteries expressed β- galactosidase. Exposure of jugular veins and carotid arteries in vivo to the α1AT adenovirus vector resulted in the expression of α1AT mRNA transcripts detected by Northern analysis and in the synthesis and secretion of α1AT detected by ex vivo [35S]methionine labeling. Expression with the adenovirus vectors was efficient and easily detectable 1-14 days after injection, with maximum expression at 7 days. Expression was no longer evident at 28 days. Thus, adenovirus vectors are capable of transferring exogenous genes to the endothelium of normal arteries and veins with expression for at least 2 weeks, suggesting that these vectors have the potential for a variety of cardiovascular experimental and clinical applications.

Original languageEnglish
Pages (from-to)1132-1138
Number of pages7
JournalCirculation Research
Volume72
Issue number5
Publication statusPublished - 22 Apr 1993

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Keywords

  • adenovirus
  • endothelium
  • gene expression
  • gene transfer

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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