Modulation of gene expression after replication-deficient, recombinant adenovirus-mediated gene transfer by the product of a second adenovirus vector

J. Hersh, R. G. Crystal, B. Bewig

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132 Citations (Scopus)

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-α (TNF) under the control of the early growth response 1 (EGR1) promoter, was used to regulate a transcription unit in AdIL8.βgal, an adenovirus vector in which the TNF sensitive interleukin-8 (IL-8) promoter drives the expression of β-galactosidase (β-gal). Following infection of HS24 cells with AdIL8.βgal, addition of TNF to the culture induced the expression of β-gal. Infection of HS24 cells with AdEGR1. TNF resulted in a dose-dependent secretion of TNF. Little β-gal was produced following co-infection of the cells with the control vector AdCMV. Null (expressing no specific gene) and AdIL8.βgal. In contrast, co-infection with AdIL8.βgal and AdEGR1. TNF demonstrated, for a given dose of AdIL8.βgal, increasing amounts of β-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.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalGene Therapy
Volume2
Issue number2
Publication statusPublished - 28 Mar 1995

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Keywords

  • adenovirus
  • gene therapy
  • interleukin-8
  • promoter
  • tumor necrosis factor

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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