Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint swelling and progressive destruction of cartilage and bone. Biologicals targeting cytokines and their receptors have been proven useful as specific therapies for RA. Anti-tumor necrosis factor (TNF)-alpha therapies (both anti-TNF antibodies and soluble TNF receptors) have shown clinical efficacy in 60-70% of the RA patients.

However, the need for continuous, multiple injections of a recombinant protein, the relatively high systemic doses necessary to achieve constant therapeutic levels in the joints, and the reported side effects are downsides of this therapeutic approach. In addition, there is persistent arthritis activity in one or more joints in the majority of patients despite systemic treatment. Furthermore, some patients suffer from only a few symptomatic joints and are not considered candidates for receiving systemic anti-TNF therapy.

Thus, there is a great need for innovative therapeutic approaches for intra-articular treatment of arthritis. Local over expression of anti-inflammatory proteins by synoviocytes represents an attractive approach to treatment. Synoviocytes can be readily accessed by intra-articular injection, making them good targets for gene delivery. Gene therapy can provide stable, regulated production of beneficial molecule(s).