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

• Published in: Molecular neurobiology Vol. 57; no. 4; pp. 2085 - 2100
• Main Authors: Paschon, Vera, Correia, Felipe Fernandes, Morena, Beatriz Cintra, da Silva, Victor Allisson, dos Santos, Gustavo Bispo, da Silva, Maria Cristina Carlan, Cristante, Alexandre Fogaça, Willerth, Stephanie Michelle, Perrin, Florence Evelyne, Kihara, Alexandre Hiroaki
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2020; Springer Nature B.V; Humana Press
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; CRISPR; CRISPR-Cas Systems - genetics; Designer Drugs - therapeutic use; Drug development; Gene Editing; Genetics; Humans; Inflammation; Information processing; Life Sciences; Neuralgia; Neurobiology; Neurology; Neurons and Cognition; Neurosciences; Optics; Optogenetics; Signal transduction; Spinal cord injuries; Spinal Cord Injuries - therapy; Therapeutic applications; Translational Medical Research; Trauma; Neuroprotection; Biotechnology; Translational medicine; Stem cells; Neurobiology; SCI; Cell signaling pathways; Gene therapy; Neuroregeneration
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-019-01861-w

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.