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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.

Original publication

DOI

10.1038/nbt1399

Type

Journal article

Journal

Nat Biotechnol

Publication Date

05/2008

Volume

26

Pages

549 - 551

Keywords

Animals, CpG Islands, Gene Targeting, Genetic Therapy, Inflammation, Lung, Plasmids