Gene therapy approach for intervertebral disc degeneration: An update

Abstract

Intervertebral disc degeneration is the primary cause of back pain and associated with neu-rological disorders including radiculopathy, myelopathy, and paralysis. The currently available surgical treatments predominantly include the excision of pathological discs, resulting in the function loss, immobilization, and potential additional complications due to the al-tered biomechanics. Gene therapy approach involves gene transfer into cells, affects RNA and protein synthesis of the encoded genes in the recipient cells, and facilitates biological treatment. Relatively long-exerting therapeutic effects by gene therapy are potentially ad-vantageous to treat slow progressive degenerative disc disease. In gene therapy, the delivery method and selection of target gene(s) are essential. Although gene therapy was first mediated by viral vectors, technological progress has enabled to apply nonviral vectors and poly-plex micelles for the disc. While RNA interference successfully provides specific downregu-lation of multiple genes in the disc, clustered regularly interspaced short palindromic repeats (CRISPR) system has increased attention to alter the process of intervertebral disc de-generation. Then, more recent findings of our studies have suggested autophagy, the intra-cellular self-digestion, and recycling system under the negative regulation by the mammalian target of rapamycin (mTOR), as a gene therapy target in the disc. Here we briefly review backgrounds and applications of gene therapy for the disc, introducing strategies of autoph-agy and mTOR signaling modulation through selective RNA interference.