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Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors

Abstract

With sweeping advances in precision delivery systems and manipulation of the genomes and transcriptomes of various cell types, medical biotechnology offers unprecedented selectivity for and control of a wide variety of biological processes, forging new opportunities for therapeutic interventions. This perspective summarizes state-of-the-art gene therapies enabled by recent innovations, with an emphasis on the expanding universe of molecular targets that govern the activity and function of primary sensory neurons and which might be exploited to effectively treat chronic pain.

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Fig. 1: Major molecular targets for gene therapy of chronic pain in primary sensory neurons.
Fig. 2: Illustration of major gene therapy approaches used in preclinical models of chronic pain.
Fig. 3: Neurobiological mechanisms underlying chronic pain in primary sensory neurons and related changes in their activity, presenting targets for gene therapy.

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Acknowledgements

Work in the authors’ laboratories has been supported in part by Innovation Fund Award and Research Excellence Framework, the University of Greenwich, UK (S.V.O.), and research support from the Rehabilitation Research Service and Biomedical Laboratory Research Service, Dept. of Veterans Affairs (S.G.W.) and by grants from the NIH, The Erythromelalgia Association (S.G.W.) and the Nancy Davis Foundation (S.G.W.). The writing of this article by S.G.W. was supported by the Bridget Marie Flaherty Professorship at Yale.

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During the past twelve months, S.G.W. has served on the scientific advisory boards of OliPass Corp., Navega Therapeutics and Medtronic, and has served as an adviser to Sangamo Therapeutics, Exicure, Alnylam Pharmaceuticals, Chromocell, Ionis Pharmaceuticals and Replay Therapeutics.

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Ovsepian, S.V., Waxman, S.G. Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors. Nat Rev Neurosci 24, 252–265 (2023). https://doi.org/10.1038/s41583-022-00673-7

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