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

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 inflamm...

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Main Authors: Hyde, Stephen C., Pringle, Ian A., Abdullah, Syahril, Lawton, Anna E., Davies, Lee A., Varathalingam, Anusha, Nunez-Alonso, Graciela A., Green, Anne Marie, Bazzani, Reto P., Sumner-Jones, Stephanie G., Chan, Mario, Hong, Yu Li, Yew, Nelson S., Cheng, Seng H., Boyd, Christopher A., Davies, Jane C., Griesenbach, Uta, Porteous, David John, Sheppard, David N., Munkonge, Felix M., Alton, Eric W. F. W., Gill, Deborah R.
Format: Article
Language:English
English
Published: Nature Publishing Group 2008
Online Access:http://psasir.upm.edu.my/id/eprint/13817/1/CpG.pdf
http://psasir.upm.edu.my/id/eprint/13817/
http://www.nature.com/nbt/index.html
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Summary: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.