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A comparative study on intra‐articular versus systemic gene electrotransfer in experimental arthritis
Author(s) -
Khoury M.,
Bigey P.,
LouisPlence P.,
Noel D.,
Rhinn H.,
Scherman D.,
Jorgensen C.,
Apparailly F.
Publication year - 2006
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.922
Subject(s) - arthritis , transgene , genetic enhancement , in vivo , recombinant dna , plasmid , gene delivery , medicine , kinetics , rheumatoid arthritis , gene , chemistry , microbiology and biotechnology , immunology , biology , biochemistry , physics , quantum mechanics
Abstract Background Electric pulse mediated gene transfer has been applied successfully in vivo for increasing naked DNA administration in various tissues. To achieve non‐viral gene transfer into arthritic joint tissue, we investigated the use of electrotransfer (ET). Because anti‐inflammatory cytokine strategies have proven efficient in experimental models of arthritis, we compared the therapeutic efficiency of local versus systemic delivery of the interleukin‐10 (IL‐10) using in vivo ET. Methods A plasmid vector expressing IL‐10 was transferred into DBA/1 mouse knee joints by ET with 12 pulses of variable duration and voltage. The kinetics of transgene expression were analyzed by specific enzyme‐linked immunosorbent assay (ELISA) in sera and knees. Optimal conditions were then used to deliver increasing amounts of IL‐10 plasmid intra‐articularly (i.a.) in the collagen‐induced arthritis (CIA) mouse model. The therapeutic efficiency was compared with the potency of intra‐muscular (i.m.) ET. Results Following i.a. ET, local IL‐10 secretion peaked on day 7 and dropped 2 weeks after. A second ET produced the same kinetics without enhancing gene transfer efficiency, while transgene was still detected in injected muscles 4 weeks after ET. Only the i.m. ET of 25 µg of IL‐10 significantly inhibited all the clinical and biological features of arthritis. The i.a. ET only showed mild improvement of arthritis when 100 µg of IL‐10 plasmid were electrotransfered weekly from day 18 following arthritis induction. Conclusions The present results suggest that gene transfer into arthritic joints by ET is an effective means to deliver anti‐inflammatory cytokines. However, short duration of transgene expression impedes a significant effect for the treatment of arthritis, making i.m. ET more potent than i.a. ET for clinical benefit in CIA. Copyright © 2006 John Wiley & Sons, Ltd.