Conversion of glial cells into functional neurons represents a potential therapeutic approach to replenish 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.
The Yang Hui team from Institute of Neuroscience, Chinese Academy of Sciences, reported 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, gliato-neuron conversion by CasRx-mediated Ptbp1 knockdown represents a promising in vivo genetic approach to treat a variety of disorders due to neuronal loss.