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. Munkonge; E. W. Alton; D. R. Gill

doi:10.1038/nbt1399

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 journal › Article › peer-review

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.

Original language	English
Pages (from-to)	549-551
Number of pages	3
Journal	Nature Biotechnology
Volume	26
Issue number	5
DOIs	https://doi.org/10.1038/nbt1399
Publication status	Published - 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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10.1038/nbt1399

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18438402

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Hyde, S. C., Pringle, I. A., Abdullah, S., Lawton, A. E., Davies, L. A., Varathalingam, A., Nunez-Alonso, G., Green, A. M., Bazzani, R. P., Sumner-Jones, S. G., Chan, M., Li, H., Yew, N. S., Cheng, S. H., Boyd, A. C., Davies, J. C., Griesenbach, U., Porteous, D. J., Sheppard, D. N., ... Gill, D. R. (2008). CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression. Nature Biotechnology, 26(5), 549-551. https://doi.org/10.1038/nbt1399

@article{9fd122b5b4f6411d94f421b2a83f8add,

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.",

keywords = "Animals CpG Islands/*genetics Gene Targeting/*methods Gene Therapy/*methods Inflammation/*genetics/*prevention \& control Lung/*metabolism Plasmids/*genetics/*therapeutic use",

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

note = "May CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression 1546-1696 (Electronic) Journal Article Research Support, Non-U.S. Gov't Review",

year = "2008",

month = apr,

doi = "10.1038/nbt1399",

language = "English",

volume = "26",

pages = "549--551",

journal = "Nature Biotechnology",

publisher = "Nature Publishing Group",

number = "5",

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Hyde, SC, Pringle, IA, Abdullah, S, Lawton, AE, Davies, LA, Varathalingam, A, Nunez-Alonso, G, Green, AM, Bazzani, RP, Sumner-Jones, SG, Chan, M, Li, H, Yew, NS, Cheng, SH, Boyd, AC, Davies, JC, Griesenbach, U, Porteous, DJ, Sheppard, DN, Munkonge, FM, Alton, EW & Gill, DR 2008, 'CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression', Nature Biotechnology, vol. 26, no. 5, pp. 549-551. https://doi.org/10.1038/nbt1399

TY - JOUR

T1 - CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression

AU - Hyde, S. C.

AU - Pringle, I. A.

AU - Abdullah, S.

AU - Lawton, A. E.

AU - Davies, L. A.

AU - Varathalingam, A.

AU - Nunez-Alonso, G.

AU - Green, A. M.

AU - Bazzani, R. P.

AU - Sumner-Jones, S. G.

AU - Chan, M.

AU - Li, H.

AU - Yew, N. S.

AU - Cheng, S. H.

AU - Boyd, A. C.

AU - Davies, J. C.

AU - Griesenbach, U.

AU - Porteous, D. J.

AU - Sheppard, D. N.

AU - Munkonge, F. M.

AU - Alton, E. W.

AU - Gill, D. R.

N1 - May CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression 1546-1696 (Electronic) Journal Article Research Support, Non-U.S. Gov't Review

PY - 2008/4

Y1 - 2008/4

N2 - 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.

AB - 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.

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

UR - https://www.scopus.com/pages/publications/43449111490

U2 - 10.1038/nbt1399

DO - 10.1038/nbt1399

M3 - Article

VL - 26

SP - 549

EP - 551

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 5

ER -

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

Abstract

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