Filter and export

Publications

What is a Publication?
1 Publication visible to you, out of a total of 1
Parkinson's disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons.

Abstract (Expand)

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.

Authors: Jessica Giehrl-Schwab, Florian Giesert, Benedict Rauser, Chu Lan Lao, Sina Hembach, Sandrine Lefort, Ignacio L Ibarra, Christina Koupourtidou, Malte Daniel Luecken, Dong-Jiunn Jeffery Truong, Judith Fischer-Sternjak, Giacomo Masserdotti, Nilima Prakash, Jovica Ninkovic, Sabine M Hölter, Daniela M Vogt Weisenhorn, Fabian J Theis, Magdalena Götz, Wolfgang Wurst

Date Published: 9th May 2022

Publication Type: Journal

Powered by
 (v.1.15.0)
About FAIRDOM | About SyNergy - Cluster for Systems Neurology | Funding and Programmes | Credits
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH