Application of the gene editing tool, CRISPR-Cas9, for treating neurodegenerative diseases

Nivya Kolli; Ming Lu; Panchanan Maiti; Julien Rossignol; Gary L Dunbar

doi:10.1016/j.neuint.2017.07.007

Application of the gene editing tool, CRISPR-Cas9, for treating neurodegenerative diseases

Neurochem Int. 2018 Jan:112:187-196. doi: 10.1016/j.neuint.2017.07.007. Epub 2017 Jul 18.

Authors

Nivya Kolli¹, Ming Lu², Panchanan Maiti³, Julien Rossignol⁴, Gary L Dunbar⁵

Affiliations

¹ Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, USA; Program in Neuroscience, Central Michigan University, Mount Pleasant, MI, USA.
² Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, USA; Program in Neuroscience, Central Michigan University, Mount Pleasant, MI, USA; Department of Psychology, Central Michigan University, Mount Pleasant, MI, USA.
³ Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, USA; Program in Neuroscience, Central Michigan University, Mount Pleasant, MI, USA; Field Neurosciences Inst., 4677 Towne Centre Rd., Suite 101, Saginaw, MI, USA; Department of Biology, Saginaw Valley State University, Saginaw, MI, USA.
⁴ Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, USA; Program in Neuroscience, Central Michigan University, Mount Pleasant, MI, USA; College of Medicine, Central Michigan University, Mount Pleasant, MI, USA.
⁵ Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI, USA; Program in Neuroscience, Central Michigan University, Mount Pleasant, MI, USA; Department of Psychology, Central Michigan University, Mount Pleasant, MI, USA; Field Neurosciences Inst., 4677 Towne Centre Rd., Suite 101, Saginaw, MI, USA. Electronic address: dunba1g@cmich.edu.

PMID: 28732771
DOI: 10.1016/j.neuint.2017.07.007

Abstract

Increased accumulation of transcribed protein from the damaged DNA and reduced DNA repair capability contributes to numerous neurological diseases for which effective treatments are lacking. Gene editing techniques provide new hope for replacing defective genes and DNA associated with neurological diseases. With advancements in using such editing tools as zinc finger nucleases (ZFNs), meganucleases, and transcription activator-like effector nucleases (TALENs), etc., scientists are able to design DNA-binding proteins, which can make precise double-strand breaks (DSBs) at the target DNA. Recent developments with the CRISPR-Cas9 gene-editing technology has proven to be more precise and efficient when compared to most other gene-editing techniques. Two methods, non-homologous end joining (NHEJ) and homology-direct repair (HDR), are used in CRISPR-Cas9 system to efficiently excise the defective genes and incorporate exogenous DNA at the target site. In this review article, we provide an overview of the CRISPR-Cas9 methodology, including its molecular mechanism, with a focus on how in this gene-editing tool can be used to counteract certain genetic defects associated with neurological diseases. Detailed understanding of this new tool could help researchers design specific gene editing strategies to repair genetic disorders in selective neurological diseases.

Keywords: DNA repair; Gene editing; Gene mutation; Genetic engineering; Neurodegenerative diseases.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
CRISPR-Cas Systems / genetics*
Cells, Cultured
Gene Editing / methods*
Gene Editing / trends
Genetic Therapy / methods*
Genetic Therapy / trends
Humans
Neurodegenerative Diseases / genetics*
Neurodegenerative Diseases / pathology
Neurodegenerative Diseases / therapy*
Neurons / pathology
Neurons / physiology
Treatment Outcome