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CRISPR, Prime Editing, Optogenetics, and DREADDs: New Therapeutic Approaches Provided by Emerging Technologies in the Treatment of Spinal Cord Injury

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Abstract

Spinal cord injury (SCI) causes temporary disabilities or permanent effects including neuropathic pain and spastiscity. The damage often results from mechanical trauma, which in turn triggers the neuroinflammatory process. Neuroinflammation plays essential roles in the structural, biochemical, and cellular changes that take place in the spinal cord after the injury. Indeed, SCI activates many different signaling pathways that coordinate the resulting cellular responses. While neuroinflammation serves as a physiological reaction to harmful stimuli, it is clear that long-lasting inflammatory response leads to aggravation of the neurodegenerative processes, becoming detrimental to recovery post-injury. In this context, we present some possible therapeutic targets in these activated signaling pathways and provide new perspectives for SCI treatment based on recently developed technologies, including clustered regularly interspaced short palindromic repeats (CRISPR)-based methods (including prime editing), optogenetics, and designer receptor exclusively activated by designer drugs (DREADDs). We critically analyze the recent advances in the deployment of these methods focusing on the control of the initial neuroinflammatory response. We then propose alternatives and provide new avenues for SCI treatment based on these emerging technologies.

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Acknowledgements

The authors thank Silva Honda Takada, Erika Reime Kinjo, Guilherme Shigueto Villar Higa, Mariana Sacrini A. Ferraz, and Fernando da Silva Borges for scientific discussions.

Funding

This work was financially supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, no. 2017/26439-0), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, no. 431000/2016-6), and research scholarships from Universidade Federal do ABC (UFABC). Dr. Willerth receives funding from NSERC, the Canada Research Chairs program, and the Alzheimer’s Association.

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Author notes

  1. Vera Paschon and Felipe Fernandes Correia contributed equally to this work.

Authors and Affiliations

  1. Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Bernardo do Campo, Brazil

    Vera Paschon, Felipe Fernandes Correia, Beatriz Cintra Morena, Victor Allisson da Silva & Alexandre Hiroaki Kihara

  2. Instituto de Ortopedia e Traumatologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Gustavo Bispo dos Santos & Alexandre Fogaça Cristante

  3. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, São Bernardo do Campo, Brazil

    Maria Cristina Carlan da Silva

  4. Department of Mechanical Engineering and Division of Medical Sciences, University of Victoria, Victoria, B.C, V8W 2Y2, Canada

    Stephanie Michelle Willerth

  5. EPHE, INSERM U1198, University of Montpellier, F-34095, Montpellier, France

    Florence Evelyne Perrin

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  9. Florence Evelyne Perrin
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  10. Alexandre Hiroaki Kihara
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Corresponding authors

Correspondence to Alexandre Fogaça Cristante, Stephanie Michelle Willerth, Florence Evelyne Perrin or Alexandre Hiroaki Kihara.

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Paschon, V., Correia, F.F., Morena, B.C. et al. CRISPR, Prime Editing, Optogenetics, and DREADDs: New Therapeutic Approaches Provided by Emerging Technologies in the Treatment of Spinal Cord Injury. Mol Neurobiol 57, 2085–2100 (2020). https://doi.org/10.1007/s12035-019-01861-w

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