Brief Communications abstract
Nature Biotechnology 26, 549 - 551 (2008)
Published online: 27 April 2008 | doi:10.1038/nbt1399
CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression
Stephen C Hyde1,6,8, Ian A Pringle1,6,8, Syahril Abdullah1,6,7,8, Anna E Lawton1,6,8, Lee A Davies1,6, Anusha Varathalingam1,6, Graciela Nunez-Alonso1,6, Anne-Marie Green1,6, Reto P Bazzani1,6, Stephanie G Sumner-Jones1,6, Mario Chan2,6, Hongyu Li3, Nelson S Yew4, Seng H Cheng4, A Christopher Boyd5,6, Jane C Davies2,6, Uta Griesenbach2,6, David J Porteous5,6, David N Sheppard3, Felix M Munkonge2,6, Eric W F W Alton2,6 & Deborah R Gill1,6
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.
- Gene Medicine Research Group, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK.
- Department of Gene Therapy, Faculty of Medicine at the National Heart and Lung Institute, Imperial College, London SW3 6LR, UK.
- Department of Physiology & Pharmacology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
- Genzyme Corporation, 49 New York Avenue, Framingham, Massachusetts 01701-9322, USA.
- Medical Sciences (Medical Genetics), University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
- UK Cystic Fibrosis Gene Therapy Consortium http://www.cfgenetherapy.org.uk/.
- Present address: Clinical Genetics Unit, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM, Malaysia.
- These authors contributed equally to this work.
Correspondence to: Stephen C Hyde1,6,8 e-mail: steve.hyde@ndcls.ox.ac.uk
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