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

S. C. Hyde, I. A. Pringle, S. Abdullah, A. E. Lawton, L. A. Davies, A. Varathalingam, G. Nunez-Alonso, A. M. Green, R. P. Bazzani, S. G. Sumner-Jones, M. Chan, H. Li, N. S. Yew, S. H. Cheng, A. C. Boyd, J. C. Davies, U. Griesenbach, D. J. Porteous, D. N. Sheppard, F. M. MunkongeE. W. Alton, D. R. Gill

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)549-551
Number of pages3
JournalNature Biotechnology
Volume26
Issue number5
DOIs
Publication statusPublished - Apr 2008

Keywords / Materials (for Non-textual outputs)

  • Animals CpG Islands/*genetics Gene Targeting/*methods Gene Therapy/*methods Inflammation/*genetics/*prevention & control Lung/*metabolism Plasmids/*genetics/*therapeutic use

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