title: CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.
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.
authors.affiliation: Gene Medicine Research Group, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK. steve.hyde@ndcls.ox.ac.uk
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Hyde
authors.forename: Ian A
authors.initials: IA
authors.lastname: Pringle
authors.forename: Syahril
authors.initials: S
authors.lastname: Abdullah
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lawton
authors.forename: Lee A
authors.initials: LA
authors.lastname: Davies
authors.forename: Anusha
authors.initials: A
authors.lastname: Varathalingam
authors.forename: Graciela
authors.initials: G
authors.lastname: Nunez-Alonso
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Green
authors.forename: Reto P
authors.initials: RP
authors.lastname: Bazzani
authors.forename: Stephanie G
authors.initials: SG
authors.lastname: Sumner-Jones
authors.forename: Mario
authors.initials: M
authors.lastname: Chan
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.forename: Nelson S
authors.initials: NS
authors.lastname: Yew
authors.forename: Seng H
authors.initials: SH
authors.lastname: Cheng
authors.forename: A Christopher
authors.initials: AC
authors.lastname: Boyd
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
authors.forename: Uta
authors.initials: U
authors.lastname: Griesenbach
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: David N
authors.initials: DN
authors.lastname: Sheppard
authors.forename: Felix M
authors.initials: FM
authors.lastname: Munkonge
authors.forename: Eric W F W
authors.initials: EW
authors.lastname: Alton
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Gill
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000235:genetics*; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D007249:Inflammation / Q000235:genetics* / Q000517:prevention & control*; D008168:Lung / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics* / Q000627:therapeutic use*