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 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.
Hyde
Stephen C
SC
Gene Medicine Research Group, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK. steve.hyde@ndcls.ox.ac.uk
Pringle
Ian A
IA
Abdullah
Syahril
S
Lawton
Anna E
AE
Davies
Lee A
LA
Varathalingam
Anusha
A
Nunez-Alonso
Graciela
G
Green
Anne-Marie
AM
Bazzani
Reto P
RP
Sumner-Jones
Stephanie G
SG
Chan
Mario
M
Li
Hongyu
H
Yew
Nelson S
NS
Cheng
Seng H
SH
Boyd
A Christopher
AC
Davies
Jane C
JC
Griesenbach
Uta
U
Porteous
David J
DJ
Sheppard
David N
DN
Munkonge
Felix M
FM
Alton
Eric W F W
EW
Gill
Deborah R
DR
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*