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Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice.
Cell ( IF 45.5 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.cell.2020.03.024 Haibo Zhou 1 , Jinlin Su 1 , Xinde Hu 2 , Changyang Zhou 2 , He Li 2 , Zhaorong Chen 2 , Qingquan Xiao 2 , Bo Wang 2 , Wenyan Wu 2 , Yidi Sun 3 , Yingsi Zhou 1 , Cheng Tang 2 , Fei Liu 1 , Linhan Wang 2 , Canbin Feng 1 , Mingzhe Liu 1 , Sanlan Li 1 , Yifeng Zhang 1 , Huatai Xu 1 , Haishan Yao 1 , Linyu Shi 1 , Hui Yang 1
Cell ( IF 45.5 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.cell.2020.03.024 Haibo Zhou 1 , Jinlin Su 1 , Xinde Hu 2 , Changyang Zhou 2 , He Li 2 , Zhaorong Chen 2 , Qingquan Xiao 2 , Bo Wang 2 , Wenyan Wu 2 , Yidi Sun 3 , Yingsi Zhou 1 , Cheng Tang 2 , Fei Liu 1 , Linhan Wang 2 , Canbin Feng 1 , Mingzhe Liu 1 , Sanlan Li 1 , Yifeng Zhang 1 , Huatai Xu 1 , Haishan Yao 1 , Linyu Shi 1 , Hui Yang 1
Affiliation
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Conversion of glial cells into functional neurons represents a potential therapeutic approach for replenishing neuronal loss associated with neurodegenerative diseases and brain injury. Previous attempts in this area using expression of transcription factors were hindered by the low conversion efficiency and failure of generating desired neuronal types in vivo. Here, we report that downregulation of a single RNA-binding protein, polypyrimidine tract-binding protein 1 (Ptbp1), using in vivo viral delivery of a recently developed RNA-targeting CRISPR system CasRx, resulted in the conversion of Müller glia into retinal ganglion cells (RGCs) with a high efficiency, leading to the alleviation of disease symptoms associated with RGC loss. Furthermore, this approach also induced neurons with dopaminergic features in the striatum and alleviated motor defects in a Parkinson's disease mouse model. Thus, glia-to-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach for treating a variety of disorders due to neuronal loss.
中文翻译：
通过CRISPR-CasRx进行的神经胶质到神经元转化可减轻小鼠神经系统疾病的症状。
胶质细胞转化为功能性神经元代表了一种潜在的治疗方法，可用于补充与神经退行性疾病和脑损伤相关的神经元丢失。低转换效率和在体内无法产生所需神经元类型的阻碍了以前使用转录因子表达在该领域的尝试。在这里，我们报告说，使用最近开发的靶向RNA的CRISPR系统CasRx的体内病毒递送，单个RNA结合蛋白，聚嘧啶束结合蛋白1（Ptbp1）的下调导致了Müller胶质细胞转化为视网膜神经节。细胞（RGC）的效率很高，从而减轻了与RGC丢失有关的疾病症状。此外，这种方法还诱导了纹状体具有多巴胺能特征的神经元，并减轻了帕金森氏病小鼠模型中的运动缺陷。因此，由CasRx介导的Ptbp1敲低引起的神经胶质到神经元的转化代表了一种有前途的体内遗传方法，可用于治疗由于神经元丢失而引起的各种疾病。
更新日期：2020-04-08
中文翻译：
通过CRISPR-CasRx进行的神经胶质到神经元转化可减轻小鼠神经系统疾病的症状。
胶质细胞转化为功能性神经元代表了一种潜在的治疗方法，可用于补充与神经退行性疾病和脑损伤相关的神经元丢失。低转换效率和在体内无法产生所需神经元类型的阻碍了以前使用转录因子表达在该领域的尝试。在这里，我们报告说，使用最近开发的靶向RNA的CRISPR系统CasRx的体内病毒递送，单个RNA结合蛋白，聚嘧啶束结合蛋白1（Ptbp1）的下调导致了Müller胶质细胞转化为视网膜神经节。细胞（RGC）的效率很高，从而减轻了与RGC丢失有关的疾病症状。此外，这种方法还诱导了纹状体具有多巴胺能特征的神经元，并减轻了帕金森氏病小鼠模型中的运动缺陷。因此，由CasRx介导的Ptbp1敲低引起的神经胶质到神经元的转化代表了一种有前途的体内遗传方法，可用于治疗由于神经元丢失而引起的各种疾病。
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