CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression

Nat Biotechnol. 2008 May;26(5):549-51. doi: 10.1038/nbt1399. Epub 2008 Apr 27.


Pulmonary delivery of plasmid DNA (pDNA)/cationic liposome complexes is associated with an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response and brief duration of transgene expression. We demonstrate that retention of even a single CpG in pDNA is sufficient to elicit an inflammatory response, whereas CpG-free pDNA vectors do not. Using a CpG-free pDNA expression vector, we achieved sustained (>or=56 d) in vivo transgene expression in the absence of lung inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CpG Islands / genetics*
  • Gene Targeting / methods*
  • Genetic Therapy / methods*
  • Inflammation / genetics*
  • Inflammation / prevention & control*
  • Lung / metabolism*
  • Plasmids / genetics*
  • Plasmids / therapeutic use*