Literature DB >> 18438402

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

Stephen C Hyde1, Ian A Pringle, Syahril Abdullah, Anna E Lawton, Lee A Davies, Anusha Varathalingam, Graciela Nunez-Alonso, Anne-Marie Green, Reto P Bazzani, Stephanie G Sumner-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.   

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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Year:  2008        PMID: 18438402     DOI: 10.1038/nbt1399

Source DB:  PubMed          Journal:  Nat Biotechnol        ISSN: 1087-0156            Impact factor:   54.908


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