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Intra‐articular electrotransfer of plasmid encoding soluble TNF receptor variants in normal and arthritic mice
Author(s) -
Bloquel C.,
Denys A.,
Boissier M. C.,
Apparailly F.,
Bigey P.,
Scherman D.,
Bessis N.
Publication year - 2007
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1088
Subject(s) - plasmid , genetic enhancement , rheumatoid arthritis , transgene , arthritis , tumor necrosis factor alpha , luciferase , gene , secretion , receptor , microbiology and biotechnology , medicine , transfection , recombinant dna , cancer research , chemistry , immunology , biology , biochemistry
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‐α‐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 © 2007 John Wiley & Sons, Ltd.