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

2008; Nature Portfolio; Volume: 26; Issue: 5 Linguagem: Inglês

10.1038/nbt1399

1546-1696

Stephen C. Hyde, Ian A. Pringle, Syahril Abdullah, Anna E. Lawton, Lee A. Davies, Anusha Varathalingam, G. Nunez-Alonso, Anne-Marie Green, Reto P. Bazzani, Stephanie Jones, Mario Chan, Hongyu Li, Nelson S. Yew, Seng H. Cheng, A. Christopher Boyd, Jane C. Davies, Uta Griesenbach, David J. Porteous, David N. Sheppard, Felix M. Munkonge, Eric W.F.W. Alton, Deborah R. Gill,

Neonatal Respiratory Health Research

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 (≥56 d) in vivo transgene expression in the absence of lung inflammation.