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 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.
Neurochem Int. 2018 Jan;112:187-196. doi: 10.1016/j.neuint.2017.07.007. Epub 2017 Jul 18.
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.
受损 DNA 中转录蛋白的积累增加和 DNA 修复能力的降低导致了许多缺乏有效治疗方法的神经疾病。基因编辑技术为替换与神经疾病相关的缺陷基因和 DNA 提供了新的希望。随着锌指核酸酶（ZFNs）、巨型核酸酶和转录激活因子样效应核酸酶（TALENs）等编辑工具的应用进展，科学家们能够设计出能够在目标 DNA 处产生精确双链断裂（DSBs）的 DNA 结合蛋白。与大多数其他基因编辑技术相比，最近开发的 CRISPR-Cas9 基因编辑技术被证明更加精确和高效。CRISPR-Cas9 系统中使用了两种方法，非同源末端连接（NHEJ）和同源定向修复（HDR），以有效地切除缺陷基因并在外源 DNA 整合到目标位点。在这篇综述文章中，我们提供了对 CRISPR-Cas9 方法学的概述，包括其分子机制，并重点介绍了如何在这个基因编辑工具中用于对抗某些与神经疾病相关的遗传缺陷。对这个新工具的详细了解可以帮助研究人员设计特定的基因编辑策略，以修复选择性神经疾病中的遗传障碍。
