Background Anti-inflammatory gene therapy is promising in inflammatory diseases such as rheumatoid arthritis (RA). We have previously demonstrated that intra-muscular (im) electrotransfer (ET) of plasmids encoding three different human tumor necrosis factor-α-soluble receptor I variants (hTNFRIs) 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 (ia) gene therapy by electrotransfer using the hTNFR-Is plasmids.

Methods and results We evaluated targeting of mice joints by CCD optical imaging after ia 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 ia ET than after im ET. A longer protein secretion could be achieved with several ia ETs. Also, we observed that hTNFR-Is expression within arthritic joints was slightly higher than in normal joints.