Non viral gene therapy in arthritis by in vivo intramuscular IL-10 DNA electrotransfer

Intramuscular electroporation of DNA is an attractive technique for nonviral gene transfer of therapeutic genes in inflammatory/autoimmune disease such as rheumatoid arthritis (RA). We have developed in vivo electroporation for efficient cytokine gene transfer in collagen induced arthritis.

Methods

We co-injected in the tibialis anterior of DBA1 mice a standard 30 ml dose of plasmid DNA encoding the anti-inflammatory cytokine viral interleukin-10 (vIL-10) under the control of a doxycycline-inducible promoter, and a plasmid expressing the tetracycline controlled transcriptional silencer (tTS) that binds promoter in absence of doxycycline. Electroporation was performed in vivo using 8 pulses of 200 v during 1 ms day 25 postimmunization of DBA1 mice with collagen type II.

Results

Electroporation resulted in a dose-dependent increase in the vIL-10 expression in muscle and serum. The transgene was expressed only by muscle cells during 4 weeks. The doxycycline treatment showed significant inhibitory effects on DBA1 mice type II collagen induced arthritis (CIA) as paw swelling was reduced (1.79 ± 0.22 vs. 2.13 ± 0.84 mm on day 32 postimmunization) and onset of arthritis clinical delayed in the doxycycline-treated group compared with the control group without doxycycline (32.62 ± 4.50 days, versus 28.38 ± 3.62 days respectively).

Conclusions

Muscle-targeted vIL10-rtTA plasmid transfer by in vivo electroporation is a suitable approach for non viral gene therapy in arthritis.