Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice
| Autor: | Hua-Tai Xu, Mingzhe Liu, Zhaorong Chen, Yifeng Zhang, Haishan Yao, Yingsi Zhou, B. D. Wang, Jinlin Su, Yidi Sun, Linyu Shi, He Li, Qingquan Xiao, Cheng Tang, Haibo Zhou, Fei Liu, Sanlan Li, Wenyan Wu, Xinde Hu, Canbin Feng, Linhan Wang, Hui Yang, Changyang Zhou |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Retinal Ganglion Cells Parkinson's disease Dopamine Neurogenesis Striatum Biology Retinal ganglion General Biochemistry Genetics and Molecular Biology Heterogeneous-Nuclear Ribonucleoproteins 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation medicine Animals Clustered Regularly Interspaced Short Palindromic Repeats Cells Cultured 030304 developmental biology Neurons 0303 health sciences Gene knockdown Cell Differentiation Parkinson Disease PTBP1 medicine.disease Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure nervous system Gene Expression Regulation Neuron CRISPR-Cas Systems Nervous System Diseases Neuroscience Muller glia Neuroglia 030217 neurology & neurosurgery Polypyrimidine Tract-Binding Protein |
| Zdroj: | Cell. 181(3) |
| ISSN: | 1097-4172 |
| Popis: | Summary 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 Muller 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. |
| Databáze: | OpenAIRE |
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