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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
Arthritis Res Ther. 2004; 6(5): 183–196.
Published online Jul 29, 2004. doi:  10.1186/ar1214
PMCID: PMC546285
Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients?
Fons AJ van de Loo,corresponding author1 Ruben L Smeets,1 and Wim B van den Berg1
1Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands
corresponding authorCorresponding author.
Fons AJ van de Loo: A.vandeloo/at/
Received May 7, 2004; Revisions requested June 17, 2004; Revised June 21, 2004; Accepted June 21, 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.
Keywords: arthritis, cytokines, gene therapy, genetic synovectomy, transcriptional regulation
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