CRISPR-Cas9 Gene Editing Protects from the A53T-SNCA Overexpression-Induced Pathology of Parkinson's Disease In Vivo.
CRISPR J
; 5(1): 95-108, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-35191750
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
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Alfa-Sinucleína
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Edición Génica
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
CRISPR J
Año:
2022
Tipo del documento:
Article