Modulation of gene expression after replication-deficient, recombinant adenovirus-mediated gene transfer by the product of a second adenovirus vector. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bronchial Neoplasms
  • Carcinoma, Squamous Cell
  • DNA, Viral
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Gene Transfer Techniques
  • Humans
  • Interleukin-8
  • Mice
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Tumor Cells, Cultured
  • Virus Replication
  • beta-Galactosidase

MeSH Major

  • Adenoviruses, Human
  • DNA, Recombinant
  • Defective Viruses
  • Gene Expression Regulation, Viral
  • Genetic Vectors
  • Helper Viruses
  • Immediate-Early Proteins
  • Tumor Necrosis Factor-alpha

abstract

  • To regulate gene expression following adenovirus-mediated gene transfer, a strategy was devised utilizing co-infection with two separate adenovirus vectors designed such that the product of one vector modulated the promoter of the second vector. To evaluate this strategy, AdEGR1.TNF, an adenovirus expressing tumor necrosis factor-alpha (TNF) under the control of the early growth response 1 (EGR1) promoter, was used to regulate a transcription unit in AdIL8.beta gal, an adenovirus vector in which the TNF sensitive interleukin-8 (IL-8) promoter drives the expression of beta-galactosidase (beta-gal). Following infection of HS24 cells with AdIL8.beta gal, addition of TNF to the culture induced the expression of beta-gal. Infection of HS24 cells with AdEGR1.TNF resulted in a dose-dependent secretion of TNF. Little beta-gal was produced following co-infection of the cells with the control vector AdCMV.Null (expressing no specific gene) and AdIL8.beta gal. In contrast, co-infection with AdIL8.beta gal and AdEGR1.TNF demonstrated, for a given dose of AdIL8.beta gal, increasing amounts of beta-gal expression dependent on the dose of AdEGR1.TNF. This model suggests control of gene expression in adenovirus-mediated gene transfer can be regulated by utilizing a promoter-gene expression cassette in one vector that modulates the expression of a promoter-gene expression cassette in a second vector.

publication date

  • March 1995

has subject area

  • Adenoviruses, Human
  • Animals
  • Bronchial Neoplasms
  • Carcinoma, Squamous Cell
  • DNA, Recombinant
  • DNA, Viral
  • DNA-Binding Proteins
  • Defective Viruses
  • Early Growth Response Protein 1
  • Gene Expression Regulation, Viral
  • Gene Transfer Techniques
  • Genetic Vectors
  • Helper Viruses
  • Humans
  • Immediate-Early Proteins
  • Interleukin-8
  • Mice
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha
  • Virus Replication
  • beta-Galactosidase

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 7719929

Additional Document Info

start page

  • 124

end page

  • 131

volume

  • 2

number

  • 2