A two-component expression system that responds to inflammatory stimuli in vivo

Alan W. Varley, Steven M. Geiszler, Richard B. Gaynor, Robert S. Munford

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

A therapeutic dilemma often complicates the management of inflammatory diseases; the benefits gained from reducing inflammation must be balanced against the potentially harmful consequences of chronic immunosuppression. Gene therapy might address this dilemma by producing anti-inflammatory proteins in response to a patient's endogenous signals, so that recombinant drug production is linked to the intensity and duration of the inflammatory condition. To test this, we have developed inflammation-inducible systems for regulating recombinant protein production in vivo. We describe a two- component expression construct in which (1) the murine complement factor 3 (C3) promoter regulates production of the human immunodeficiency virus (HIV) transactivator of transcription (Tat), and (2) the Tat protein then stimulates protein expression from genes inserted downstream of the the HIV promoter. When incorporated into a nonreplicating adenovirus (Ad.C3-tat/HIV- luc) and studied in a murine model, the construct produces large amounts of recombinant protein in vivo in response to two different inflammatory stimuli.

Original languageEnglish (US)
Pages (from-to)1002-1006
Number of pages5
JournalNature Biotechnology
Volume15
Issue number10
StatePublished - Oct 1997

Fingerprint

Viruses
Recombinant proteins
Complement C3
Trans-Activators
HIV
Transcription
Proteins
Recombinant Proteins
Inflammation
Gene therapy
Disease Management
Adenoviridae
Genetic Therapy
Immunosuppression
Anti-Inflammatory Agents
Genes
Gene Expression
Pharmaceutical Preparations
Therapeutics

Keywords

  • Acute phase response
  • Gene therapy
  • Inflammatory response

ASJC Scopus subject areas

  • Microbiology

Cite this

Varley, A. W., Geiszler, S. M., Gaynor, R. B., & Munford, R. S. (1997). A two-component expression system that responds to inflammatory stimuli in vivo. Nature Biotechnology, 15(10), 1002-1006.

A two-component expression system that responds to inflammatory stimuli in vivo. / Varley, Alan W.; Geiszler, Steven M.; Gaynor, Richard B.; Munford, Robert S.

In: Nature Biotechnology, Vol. 15, No. 10, 10.1997, p. 1002-1006.

Research output: Contribution to journalArticle

Varley, AW, Geiszler, SM, Gaynor, RB & Munford, RS 1997, 'A two-component expression system that responds to inflammatory stimuli in vivo', Nature Biotechnology, vol. 15, no. 10, pp. 1002-1006.
Varley AW, Geiszler SM, Gaynor RB, Munford RS. A two-component expression system that responds to inflammatory stimuli in vivo. Nature Biotechnology. 1997 Oct;15(10):1002-1006.
Varley, Alan W. ; Geiszler, Steven M. ; Gaynor, Richard B. ; Munford, Robert S. / A two-component expression system that responds to inflammatory stimuli in vivo. In: Nature Biotechnology. 1997 ; Vol. 15, No. 10. pp. 1002-1006.
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