Type I interferons potently suppress gene expression following gene delivery using liposome(-)DNA complexes

Mol Ther. 2005 Sep;12(3):451-9. doi: 10.1016/j.ymthe.2005.04.008.


Gene delivery by intravenous injection of cationic liposome-DNA complexes (LDC) can generate efficient transgene expression in the lungs and other organs, but the duration of expression is typically short. Previous studies have suggested a major role for interferon-gamma (IFN-gamma) and TNF in this process. However, plasmid DNA is also capable of eliciting production of type I IFNs. Therefore, we assessed the ability of LDC to elicit production of type I IFNs in vivo and assessed the effects of type I IFNs on suppression of transgene expression following in vivo gene delivery with LDC. Injection of LDC was found to induce production of high levels of both IFN-alpha and IFN-beta in vivo. Moreover, the levels of transgene expression following in vivo gene delivery were markedly increased in mice lacking functional type I IFN receptor genes, compared to wild-type mice or mice lacking IFN-gamma or TNF receptors. Addition of recombinant IFN-alpha and IFN-beta inhibited transgene expression by in vitro-transfected endothelial cells, and incubation of macrophages with LDC in vitro triggered production of both IFN-alpha and IFN-beta. Therefore, type I IFNs appear to play a key role in suppressing transgene expression in vivo following systemic nonviral gene delivery using LDC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA / chemistry*
  • DNA / metabolism
  • Dose-Response Relationship, Drug
  • Endothelial Cells / metabolism
  • Fibroblasts / metabolism
  • Gene Expression Regulation*
  • Gene Transfer Techniques
  • Genetic Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • In Vitro Techniques
  • Interferon Type I / metabolism*
  • Interferon-alpha / biosynthesis
  • Interferon-beta / biosynthesis
  • Interferon-beta / metabolism
  • Liposomes / chemistry
  • Liposomes / metabolism*
  • Luciferases / metabolism
  • Macrophages / metabolism
  • Mice
  • Plasmids / metabolism
  • Time Factors
  • Transfection
  • Transgenes


  • Interferon Type I
  • Interferon-alpha
  • Liposomes
  • Interferon-beta
  • DNA
  • Luciferases