In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors. Academic Article uri icon

Overview

MeSH

  • Animals
  • Carotid Arteries
  • DNA
  • Endothelium, Vascular
  • Escherichia coli
  • Female
  • Jugular Veins
  • Lac Operon
  • Male
  • Recombination, Genetic
  • Sheep
  • alpha 1-Antitrypsin

MeSH Major

  • Adenoviridae
  • Blood Vessels
  • Gene Expression
  • Genetic Vectors
  • Transfection
  • Virus Replication

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 alpha 1-antitrypsin (alpha 1AT) 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 beta-galactosidase. Exposure of jugular veins and carotid arteries in vivo to the alpha 1AT adenovirus vector resulted in the expression of alpha 1AT mRNA transcripts detected by Northern analysis and in the synthesis and secretion of alpha 1AT 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.

publication date

  • May 1993

has subject area

  • Adenoviridae
  • Animals
  • Blood Vessels
  • Carotid Arteries
  • DNA
  • Endothelium, Vascular
  • Escherichia coli
  • Female
  • Gene Expression
  • Genetic Vectors
  • Jugular Veins
  • Lac Operon
  • Male
  • Recombination, Genetic
  • Sheep
  • Transfection
  • Virus Replication
  • alpha 1-Antitrypsin

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 8477524

Additional Document Info

start page

  • 1132

end page

  • 1138

volume

  • 72

number

  • 5