A self-augmenting gene expression cassette for enhanced and sustained transgene expression in the presence of proinflammatory cytokines

Phoebe Luo, B. D. Reed, T. C. Tsang, D. T. Harris, R. A. Flavell

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Viral promoters can yield high gene expression levels yet tend to be attenuated in vivo by host proinflammatory cytokines. Prolonged transgene expression can be obtained using constitutive cellular promoters. However, levels of transgene expression driven by cellular promoters are insufficient for effective therapy. We designed a novel self-augmenting gene expression cassette in which the transgene product can induce an endogenous transcription factor to enhance the activity of a weak cellular promoter driving its expression. Using the cellular major histocompatibility complex class I (H-2Kb) promoter to drive the interferon (IFN-γ) cytokine gene, we show that the H-2Kb promoter, although exhibiting much lower basal activity, yields higher IFN-γ production than the CMV promoter 2 days after transfection. IFN-γ expression driven by the H-2Kb promoter also lasts longer than that driven by the cytomegalovirus promoter. Our data demonstrate that the self-augmenting strategy provides a promising approach to achieve high and sustained transgene expression in vivo.

Original languageEnglish (US)
Pages (from-to)659-667
Number of pages9
JournalDNA and Cell Biology
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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