Gene therapy for osteoarthritis

Gene therapy for osteoarthritis is the application of gene therapy to treat osteoarthritis (OA). Unlike pharmacological treatments which are administered locally or systemically as a series of interventions, gene therapy aims to establish sustained therapeutic effect after a single, local injection.^[1]

The main risk factors for osteoarthritis are age^[2][3] and body mass index,^[4][3] as such, OA is predominantly considered a disease of aging.^[5][6] As the body ages, catabolic factors begin to predominate over anabolic factors resulting in a reduction of extracellular matrix gene expression^[7] and reduced cellularity^[8][7] in articular cartilage. Catabolism eventually predominates over anabolism to such an extent that severe cartilage erosions and bone marrow lesions / remodeling manifest in clinical osteoarthritis. Joint inflammation is also a key mechanism in OA,^[9] and a number of pro-inflammatory cytokines, particularly IL-1, have been implicated in pathophysiology,^[10][11] human genetics,^[12] and animal models of disease. ^[13] In addition, osteoarthritis has a number of heritable factors, and there may be additional genetic risk factors for the disease.

Gene augmentation,^[14] gene replacement, and novel transgene gene therapy^[15] strategies for the potential medical management of osteoarthritis are under preliminary research to define pathological mechanisms and possible treatments for this chronic disease. While viral vector gene therapies predominate, both viral and non-viral vectors have been developed as a means to deliver therapeutic genes.^[16]