CRISPR-Cas9 Gene Editing Protects from the A53T-SNCA Overexpression-Induced Pathology of Parkinson's Disease in Vivo
- Authors
- Yoon, H.H.; Ye, S.; Lim, S.; Jo, A.; Lee, H.; Hong, F.; Lee, S.E.; Oh, S.-J.; Kim, N.-R.; Kim, K.; Kim, B.-J.; Kim, H.; Lee, C.J.; Nam, M.-H.; Hur, J.W.; Jeon, S.R.
- Issue Date
- Feb-2022
- Publisher
- Mary Ann Liebert Inc.
- Citation
- CRISPR Journal, v.5, no.1, pp.95 - 108
- Indexed
- SCIE
SCOPUS
- Journal Title
- CRISPR Journal
- Volume
- 5
- Number
- 1
- Start Page
- 95
- End Page
- 108
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/140163
- DOI
- 10.1089/crispr.2021.0025
- ISSN
- 2573-1599
- Abstract
- Mutations in specific genes, including synuclein alpha (SNCA) that encodes the α-synuclein protein, are known to be risk factors for sporadic Parkinson's disease (PD), as well as critical factors for familial PD. In particular, A53T-mutated SNCA (A53T-SNCA) is a well-studied familial pathologic mutation in PD. However, techniques for deletion of the mutated SNCA gene in vivo have not been developed. Here, we used the CRISPR-Cas9 system to delete A53T-SNCA in vitro as well as in vivo. Adeno-associated virus carrying SaCas9-KKH with a single-guide RNA targeting A53T-SNCA significantly reduced A53T-SNCA expression levels in vitro. Furthermore, we tested its therapeutic potential in vivo in a viral A53T-SNCA-overexpressing rat model of PD. Gene deletion of A53T-SNCA significantly rescued the overexpression of α-synuclein, reactive microgliosis, dopaminergic neurodegeneration, and parkinsonian motor symptoms. Our findings propose CRISPR-Cas9 system as a potential prevention strategy for A53T-SNCA-specific PD. © Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.
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- Appears in
Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
- College of Medicine > Department of Medical Science > 1. Journal Articles
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