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 Scopus citations

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-/Ivc) 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
DOIs
StatePublished - Oct 1997

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Keywords

  • Acute phase response
  • Gene therapy
  • Inflammatory response

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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. https://doi.org/10.1038/nbt1097-1002