Neurospine.  2020 Mar;17(1):3-14. 10.14245/ns.2040042.021.

Gene Therapy Approach for Intervertebral Disc Degeneration: An Update

• Takeoka Y
• Yurube T
• Nishida K

• KMID: 2501527
• DOI: http://doi.org/10.14245/ns.2040042.021

Abstract

Intervertebral disc degeneration is the primary cause of back pain and associated with neurological 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 altered 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 advantageous 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 polyplex micelles for the disc. While RNA interference successfully provides specific downregulation of multiple genes in the disc, clustered regularly interspaced short palindromic repeats (CRISPR) system has increased attention to alter the process of intervertebral disc degeneration. Then, more recent findings of our studies have suggested autophagy, the intracellular 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 autophagy and mTOR signaling modulation through selective RNA interference.

Keyword

Gene therapy; Viral and nonviral vector; Polyplex micelle; Clustered regularly interspaced short palindromic repeats; Autophagy and mammalian target of rapamycin signaling; Intervertebral disc degeneration and regeneration