通过 RNA 编辑缓解神经疾病。

Alleviation of neurological disease by RNA editing.

机构信息

Shenzhen Eye Hospital affiliated to Jinan University, Shenzhen, PR China.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, PR China.

出版信息

Methods. 2021 Oct;194:94-99. doi: 10.1016/j.ymeth.2021.04.023. Epub 2021 Apr 30.

DOI:10.1016/j.ymeth.2021.04.023

PMID:33933604

Abstract

The development of CRISPR/Cas genome editing tools has revolutionized the life sciences by providing transformative applications in many biological fields, including the field of neurological disorders. Compared with previous CRISPR-Cas systems targeting DNA, a new field of RNA editing using CRISPR-Cas13 systems is gaining immense popularity. CRISPR-Cas13 is a robust, precise, versatile and safe RNA guided RNA-targeting system, which uniquely targets single-strand RNA. Recently, RNA-targeted gene editing tools have been refined by the introduction of an AAV (adeno-associated virus)-based CRISPR-Cas13 system for in vivo therapeutic cell fate conversion, which has been used to treat animal models of Parkinson's disease. This flavor of gene editing showed promising effects on glia-to-neuron conversion in both intact and damaged mature retinas in a mouse model. Herein, we summarize the CRISPR-Cas13 system and its potential for applications in neurological diseases, focusing on the method of applying the AAV-mediated CRISPR-Cas13 system to the conversion of glia-to-neuron.

摘要

CRISPR/Cas 基因组编辑工具的发展通过在许多生物学领域（包括神经疾病领域）提供变革性的应用，彻底改变了生命科学。与以前针对 DNA 的 CRISPR-Cas 系统相比，使用 CRISPR-Cas13 系统进行 RNA 编辑的新领域正变得非常流行。CRISPR-Cas13 是一种强大、精确、多功能且安全的 RNA 指导的 RNA 靶向系统，它专门靶向单链 RNA。最近，通过引入基于 AAV（腺相关病毒）的 CRISPR-Cas13 系统，对 RNA 靶向基因编辑工具进行了改进，用于体内治疗性细胞命运转换，该方法已用于治疗帕金森病的动物模型。这种基因编辑方法在小鼠模型的完整和受损成熟视网膜中显示出对胶质细胞到神经元的转化有良好的效果。在此，我们总结了 CRISPR-Cas13 系统及其在神经疾病中的应用潜力，重点介绍了应用 AAV 介导的 CRISPR-Cas13 系统将胶质细胞转化为神经元的方法。