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

Hyde, Stephen C; Pringle, Ian A; Abdullah, Syahril; Lawton, Anna E; Davies, Lee A; Varathalingam, Anusha; Nunez-Alonso, Graciela; Green, Anne-Marie et al. · Nat Biotechnol · 2008

basic_science · Level V

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Abstract

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.

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