The Role of Gene Therapy in Cartilage Repair

The key principle of gene delivery to articulations by direct intra-articular injection is to release complementary DNA(cDNA)-encoding medical products that will lead to maintained, endogenous production of the gene products withinthe articulation. In fact, this has been accomplished for both in vivo and ex vivo gene delivery, using several vectors,genes, and cells in some animal models. Some clinical trials for rheumatoid arthritis and osteoarthritis (OA) usingretrovirus vectors for ex vivo gene delivery and adeno-associated virus (AAV) for in vivo delivery have been reported.AAV is of special attention because, contrary to other viral vectors, it can enter deep within joint cartilage and transducechondrocytes in situ. This quality is of special significance in OA, in which modifications in chondrocyte metabolismare believed to be crucial to the pathophysiology of the disease. The clinical effectiveness of TissueGene-C (TG-C), acell and gene therapy for OA consisting of nontransformed and transduced chondrocytes (3:1) retrovirally transducedto overexpress TGF-β1 has been reported in patients with knee OA. The most common complications of TG-C wereperipheral edema (9%), arthralgia (8%), articular swelling (6%), and injection site pain (5%). TG-C was associatedwith relevant ameliorations in function and pain. Gene therapy appears to be a viable method for the management ofarticular cartilage defects and OA.Level of evidence: III