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

Nature Biotechnology volume 15, pages 1002–1006 (1997)Cite this article

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.

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Author notes

  1. Robert S. Munford: (e-mail: RMUNF1@mednet.swmed.edu).

Authors and Affiliations

  1. Molecular Host Defense Laboratory, Infectious Disease Division, Southwestern Medical Center, Dallas, TX, 75235-9113

    Alan W. Varley & Steven M. Geiszler

  2. Molecular Virology Division, Department of Internal Medicine UT Southwestern Medical Center, Dallas, TX, 75235-9113

    Richard B. Gaynor

Authors
  1. Alan W. Varley
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  2. Steven M. Geiszler
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  3. Richard B. Gaynor
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  4. Robert S. Munford
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Varley, A., Geiszler, S., Gaynor, R. et al. A two-component expression system that responds to inflammatory stimuli in vivo. Nat Biotechnol 15, 1002–1006 (1997). https://doi.org/10.1038/nbt1097-1002

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