Yoon, Hyung Ho Ye, Sunghyeok Lim, Sunhwa Jo, Ara Lee, Hawon Hong, Felix Lee, Seung Eun Oh, Soo-Jin Kim, Na-Rae Kim, Kyoungmi Kim, Bum-Joon Kim, Hyunjin Lee, C. Justin Nam, Min-Ho Hur, Junseok W. Jeon, Sang Ryong 2024-01-19T12:33:25Z 2024-01-19T12:33:25Z 2022-06-09 2022-02 2573-1599 https://pubs.kist.re.kr/handle/201004/115638 Mutations in specific genes, including synuclein alpha (SNCA) that encodes the alpha-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 alpha-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. English Mary Ann Liebert Inc. CRISPR-Cas9 Gene Editing Protects from the A53T-SNCA Overexpression-Induced Pathology of Parkinson's Disease In Vivo Article 10.1089/crispr.2021.0025 1 CRISPR Journal, v.5, no.1, pp.95 - 108 CRISPR Journal 5 1 95 108 N scie scopus 000797625600010 2-s2.0-85125779478 Genetics & Heredity Genetics & Heredity Article ALPHA-SYNUCLEIN MOUSE MODEL RAT MODEL NEURODEGENERATION EVOLUTION MUTATION FAMILY MUSCLE A53T