Abstract：
: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.
journal_name
Celljournal_title
Cellauthors
Zhou H,Su J,Hu X,Zhou C,Li H,Chen Z,Xiao Q,Wang B,Wu W,Sun Y,Zhou Y,Tang C,Liu F,Wang L,Feng C,Liu M,Li S,Zhang Y,Xu H,Yao H,Shi L,Yang Hdoi
10.1016/j.cell.2020.03.024subject
Has Abstractpub_date
2020-04-30 00:00:00pages
590-603.e16issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(20)30286-5journal_volume
181pub_type
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