Intra-articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice.

Intra-articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice. Research Abstract Details 

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Intra-articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice. Abstract Text:

C Bloquel,A Denys,M C Boissier,F Apparailly,P Bigey,D Scherman,N Bessis,C Bloquel,A Denys,M C Boissier,F Apparailly,P Bigey,D Scherman,N Bessis,

BACKGROUND: Anti-inflammatory gene therapy is promising in inflammatory diseases such as rheumatoid arthritis (RA). We have previously demonstrated that intra-muscular (i.m.) electrotransfer (ET) of plasmids encoding three different human tumor necrosis factor-alpha-soluble receptor I variants (hTNFR-Is) exert protective effects in an experimental RA model. However, such a systemic approach could be responsible for side effects. The present study aimed at performing an intra-articular (i.a.) gene therapy by electrotransfer using the hTNFR-Is plasmids. METHODS AND RESULTS: We evaluated targeting of mice joints by CCD optical imaging after i.a. ET of a luciferase-encoding plasmid and we showed that ET led to strongly increased transgene expression in a plasmid dose-dependent manner. Moreover, articular and seric hTNFR-Is was detectable for 2 weeks. As expected, systemic hTNFR-Is rates were lower after i.a. ET than after i.m. ET. A longer protein secretion could be achieved with several i.a. ETs. Also, we observed that hTNFR-Is expression within arthritic joints was slightly higher than in normal joints. CONCLUSIONS: In collagen-induced arthritis (CIA), a mouse model for RA, we demonstrated that hTNFR-Is/mIgG1-encoding plasmid i.a. ET decreased joint destruction in the ankles. In conclusion, our results suggest that local TNFR-Is gene therapy may play a role in decreasing joint destruction in CIA. Copyright (c) 2007 John Wiley & Sons, Ltd.

Intra-articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice. Publishing Authors By Initials

C Bloquel,A Denys,MC Boissier,F Apparailly,P Bigey,D Scherman,N Bessis,C Bloquel,A Denys,MC Boissier,F Apparailly,P Bigey,D Scherman,N Bessis,

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Intra-articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The journal of gene medicine

VOLUME: 9

Page Numbers: 986-93

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ISSN: 1099-498X

DAY: 29

MONTH: Nov

YEAR: 2007

Intra-articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice. Information

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LANGUAGE: eng

NlmUniqueID: 9815764

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AFFILIATION: Inserm, Eri-18, F-93017 Bobigny, France.

Country: England

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MEDLINETA: J Gene Med

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