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Shortening the half-life of Cas9 maintains its gene editing ability and reduces neuronal toxicity

ABSTRACT: Shortening the half-life of Cas9 maintains its gene editing ability and reduces neuronal toxicity

PROVIDER: PRJNA503401 | ENA |

REPOSITORIES: ENA

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Shortening the half-life of Cas9 maintains its gene editing ability and reduces neuronal toxicity

Project description:Virus-mediated expression of CRISPR/Cas9 has been actively used for genome editing in animal models of genetic disorders, including neurological diseases, but the consequences of overexpressing bacterial Cas9 in the mammalian brain remain unknown. Through RNA-seq analysis, we found that virus-mediated expression of Cas9 caused systematic changes in genes involved in neuronal functions. We also generated a short-lived version of Cas9, which maintains its genome editing capacity, but significantly alleviates neurotoxicity caused by overexpressed Cas9. Thus, modification of Cas9 by shortening its half-life would help develop CRISPR/Cas9-based therapeutic approaches for treating genetic neurological disorders.

2018-12-04 | GSE122072 | GEO

Shortening the Half-Life of Cas9 Maintains Its Gene Editing Ability and Reduces Neuronal Toxicity.

Project description:Virus-mediated expression of CRISPR/Cas9 is commonly used for genome editing in animal brains to model or treat neurological diseases, but the potential neurotoxicity of overexpressing bacterial Cas9 in the mammalian brain remains unknown. Through RNA sequencing (RNA-seq) analysis, we find that virus-mediated expression of Cas9 influences the expression of genes involved in neuronal functions. Reducing the half-life of Cas9 by tagging with geminin, whose expression is regulated by the cell cycle, maintains the genome editing capacity of Cas9 but significantly alleviates neurotoxicity. Thus, modification of Cas9 by shortening its half-life can help develop CRISPR/Cas9-based therapeutic approaches for treating neurological disorders.

| S-EPMC6314484 | biostudies-literature

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