The Role of Gene Therapy in Cartilage Repair



1 Department of Orthopaedic Surgery and La Paz Research Institute (“Instituto de Investigación La Paz – IdiPaz”), “La Paz” University Hospital, Madrid, Spain

2 Rush University, Chicago, Illinois, USA


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 within
the 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) using
retrovirus 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 transduce
chondrocytes in situ. This quality is of special significance in OA, in which modifications in chondrocyte metabolism
are believed to be crucial to the pathophysiology of the disease. The clinical effectiveness of TissueGene-C (TG-C), a
cell and gene therapy for OA consisting of nontransformed and transduced chondrocytes (3:1) retrovirally transduced
to overexpress TGF-β1 has been reported in patients with knee OA. The most common complications of TG-C were
peripheral edema (9%), arthralgia (8%), articular swelling (6%), and injection site pain (5%). TG-C was associated
with relevant ameliorations in function and pain. Gene therapy appears to be a viable method for the management of
articular cartilage defects and OA.
Level of evidence: III


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