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

  • CJ Jorgensen1,

    Affiliated with

    • F Apparailly1,

      Affiliated with

      • N Perez2,

        Affiliated with

        • V Millet1,

          Affiliated with

          • D Greuet2,

            Affiliated with

            • C Minot2,

              Affiliated with

              • O Danos2 and

                Affiliated with

                • J Sany1

                  Affiliated with

                  Arthritis Res20024(Suppl 1):100

                  DOI: 10.1186/ar435

                  Received: 15 January 2002

                  Published: 4 February 2002

                   

                  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.

                  Authors’ Affiliations

                  (1)
                  University Hospital Montpellier
                  (2)
                  Genethon III

                  Copyright

                  © BioMed Central Ltd 2002

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