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 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.
DOIAbstract
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
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