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

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

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  • 1Gene Medicine Research Group, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK.


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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