Plate IV.244 · Publications
Parkinson's disease motor symptoms rescue by CRISPRa‐reprogramming astrocytes into GABAergic neurons
Article in EMBO Molecular Medicine, 4 April 2022.
Abstract
Direct reprogramming based on genetic factors resembles a promising strategy to replace lost cells in degenerative diseases such as Parkinson's disease. For this, we developed a knock-in mouse line carrying a dual dCas9 transactivator system (dCAM) allowing the conditional in vivo activation of endogenous genes. To enable a translational application, we additionally established an AAV-based strategy carrying intein-split-dCas9 in combination with activators (AAV-dCAS). Both approaches were successful in reprogramming striatal astrocytes into induced GABAergic neurons confirmed by single-cell transcriptome analysis of reprogrammed neurons in vivo. These GABAergic neurons functionally integrate into striatal circuits, alleviating voluntary motor behavior aspects in a 6-OHDA Parkinson's disease model. Our results suggest a novel intervention strategy beyond the restoration of dopamine levels. Thus, the AAV-dCAS approach might enable an alternative route for clinical therapies of Parkinson's disease.
Cite
@article{giehrlschwab2022parkinson,
title = {{Parkinson's disease motor symptoms rescue by CRISPRa‐reprogramming astrocytes into GABAergic neurons}},
author = {Giehrl‐Schwab, Jessica and Giesert, Florian and Rauser, Benedict and Lao, Chu Lan and Hembach, Sina and Lefort, Sandrine and Ibarra, Ignacio L and Koupourtidou, Christina and Luecken, Malte Daniel and Truong, Dong‐Jiunn Jeffery and Fischer‐Sternjak, Judith and Masserdotti, Giacomo and Prakash, Nilima and Ninkovic, Jovica and Hölter, Sabine M and Vogt Weisenhorn, Daniela M and Theis, Fabian J and Götz, Magdalena and Wurst, Wolfgang},
journal = {EMBO Molecular Medicine},
publisher = {Springer Science and Business Media LLC},
year = {2022},
month = apr,
doi = {10.15252/emmm.202114797},
url = {https://doi.org/10.15252/emmm.202114797},
pmid = {35373464},
pmcid = {PMC9081909}
}