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

被引：244

作者：

Hyde, Stephen C. ^{[1
]}

Pringle, Ian A. ^{[1
]}

Abdullah, Syahril ^{[1
]}

Lawton, Anna E. ^{[1
]}

Davies, Lee A. ^{[1
]}

Varathalingam, Anusha ^{[1
]}

Nunez-Alonso, Graciela ^{[1
]}

Green, Anne-Marie ^{[1
]}

Bazzani, Reto P. ^{[1
]}

Sumner-Jones, Stephanie G. ^{[1
]}

Chan, Mario ^{[2
]}

Li, Hongyu ^{[3
]}

Yew, Nelson S. ^{[4
]}

Cheng, Seng H. ^{[4
]}

Boyd, A. Christopher

Davies, Jane C. ^{[2
]}

Griesenbach, Uta ^{[2
]}

Porteous, David J. ^{[5
]}

Sheppard, David N. ^{[3
]}

Munkonge, Felix M. ^{[2
]}

Alton, Eric W. F. W. ^{[2
]}

Gill, Deborah R. ^{[1
]}

机构：

[1] Univ Oxford, Nuffield Dept Clin Lab Sci, Gene Med Res Grp, Oxford OX3 9DU, England

[2] Natl Heart & Lung Inst, Dept Gene Therapy, Fac Med, London SW3 6LR, England

[3] Univ Bristol, Sch Med Sci, Dept Physiol & Pharmacol, Bristol BS8 1TD, Avon, England

[4] Genzyme Corp, Framingham, MA 01701 USA

[5] Univ Edinburgh, Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland

来源：

NATURE BIOTECHNOLOGY | 2008年 / 26卷 / 05期

关键词：

D O I：

10.1038/nbt1399

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：549 / 551

页数：3

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