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  • Meeting abstract
  • Open Access

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

  • 1,
  • 1,
  • 2,
  • 1,
  • 2,
  • 2,
  • 2 and
  • 1
Arthritis Research & Therapy20024 (Suppl 1) :100

https://doi.org/10.1186/ar435

  • Received: 15 January 2002
  • Published:

Keywords

  • Rheumatoid Arthritis
  • Doxycycline
  • Collagen Induce Arthritis
  • Therapeutic Gene
  • Significant Inhibitory Effect

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, Montpellier, France
(2)
Genethon III, CNRS URA 1923, E, Evry, France

Copyright

© BioMed Central Ltd 2002

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