Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bronchi
  • DNA, Viral
  • Epithelial Cells
  • Epithelium
  • Escherichia coli
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Viral
  • Male
  • Recombination, Genetic
  • Sigmodontinae

MeSH Major

  • Adenoviruses, Human
  • Genetic Therapy
  • Genetic Vectors
  • Lung
  • Transfection
  • beta-Galactosidase

abstract

  • A variety of pulmonary disorders, including cystic fibrosis, are potentially amenable to treatment in which a therapeutic gene is directly transferred to the bronchial epithelium. This is difficult to accomplish because the majority of airway epithelial cells replicate slowly and/or are terminally differentiated. Adenovirus vectors may circumvent this problem, since they do not require target cell proliferation to express exogenous genes. To evaluate the diversity of airway epithelial cell targets for in vivo adenovirus-directed gene transfer, a replication deficient recombinant adenovirus containing the Escherichia coli lacZ (beta-galactosidase [beta-gal]) gene (Ad.RSV beta gal) was used to infect lungs of cotton rats. In contrast to uninfected animals, intratracheal Ad.RSV beta gal administration resulted in beta-gal activity in lung lysate and cytochemical staining in all cell types forming the airway epithelium. The expression of the exogenous gene was dose-dependent, and the distribution of the beta-gal positive airway epithelial cells in Ad.RSV beta gal-infected animals was similar to the normal cell differential of the control animals. Thus, a replication deficient recombinant adenovirus can transfer an exogenous gene to all major categories of airway epithelial cells in vivo, suggesting that adenovirus vectors may be an efficient strategy for in vivo gene transfer in airway disorders such as cystic fibrosis.

publication date

  • January 1993

has subject area

  • Adenoviruses, Human
  • Animals
  • Bronchi
  • DNA, Viral
  • Epithelial Cells
  • Epithelium
  • Escherichia coli
  • Female
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Viral
  • Genetic Therapy
  • Genetic Vectors
  • Lung
  • Male
  • Recombination, Genetic
  • Sigmodontinae
  • Transfection
  • beta-Galactosidase

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC330018

Digital Object Identifier (DOI)

  • 10.1172/JCI116175

PubMed ID

  • 8423221

Additional Document Info

start page

  • 225

end page

  • 234

volume

  • 91

number

  • 1