Gene therapy: what have we accomplished and where do we go from here?

As a potential treatment for arthritis, gene transfer should be viewed within the context of biological therapy. Its particular strengths include the ability to deliver therapeutic gene products, both RNA and protein, to specific cells or tissues in a targeted, sustained, and potentially regulated, cost-effective fashion. An expanded definition of gene therapy includes the delivery of noncoding nucleotide sequences that act, for example, as decoy molecules. Considerable experimental progress has been made in the preclinical development of gene therapies for arthritis. Indeed, there is overwhelming proof of principle in animal models of rheumatoid arthritis (RA) and accumulating evidence of efficacy in animal models of osteoarthritis (OA). Early-phase human clinical trials have been successfully conducted and others are in progress. Additional research is necessary to optimize gene transfer technologies and achieve regulated transgene expression. However, the most urgent need is for interventional studies in human disease and the funding with which to implement them.