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

  • Vera Paschon
  • Felipe Fernandes Correia
  • Beatriz Cintra Morena
  • Victor Allisson da Silva
  • Gustavo Bispo dos Santos
  • Maria Cristina Carlan da Silva
  • Alexandre Fogaça CristanteEmail author
  • Stephanie Michelle WillerthEmail author
  • Florence Evelyne PerrinEmail author
  • Alexandre Hiroaki KiharaEmail author
Article

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.

Keywords

SCI Cell signaling pathways Neuroprotection Neuroregeneration Biotechnology Translational medicine Stem cells Gene therapy Neurobiology 

Notes

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 Information

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.

Compliance with Ethical Standards

Disclaimer

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. 1.Centro de Matemática, Computação e CogniçãoUniversidade Federal do ABCSão Bernardo do CampoBrazil
  2. 2.Instituto de Ortopedia e TraumatologiaFaculdade de Medicina da Universidade de São PauloSão PauloBrazil
  3. 3.Centro de Ciências Naturais e HumanasUniversidade Federal do ABCSão Bernardo do CampoBrazil
  4. 4.Department of Mechanical Engineering and Division of Medical SciencesUniversity of VictoriaVictoriaCanada
  5. 5.EPHE, INSERM U1198University of MontpellierMontpellierFrance

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