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Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients?

Fons AJ van de Loo*, Ruben L Smeets and Wim B van den Berg

Author Affiliations

Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands

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Arthritis Res Ther 2004, 6:183-196  doi:10.1186/ar1214

Published: 29 July 2004


Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints, with progressive destruction of cartilage and bone. Anti-tumour necrosis factor-α therapies (e.g. soluble tumour necrosis factor receptors) ameliorate disease in 60–70% of patients with RA. However, the need for repeated systemic administration of relatively high doses in order to achieve constant therapeutic levels in the joints, and the reported side effects are downsides to this systemic approach. Several gene therapeutic approaches have been developed to ameliorate disease in animal models of arthritis either by restoring the cytokine balance or by genetic synovectomy. In this review we summarize strategies to improve transduction of synovial cells, to achieve stable transgene expression using integrating viruses such as adeno-associated viruses, and to achieve transcriptionally regulated expression so that drug release can meet the variable demands imposed by the intermittent course of RA. Evidence from animal models convincingly supports the application of gene therapy in RA, and the feasibility of gene therapy was recently demonstrated in phase I clinical trials.

arthritis; cytokines; gene therapy; genetic synovectomy; transcriptional regulation