The Role of Gene Therapy in Cartilage Repair

Abstract

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