Pluto Bioinformatics

GSE122072: Shortening the half-life of Cas9 maintains its gene editing ability and reduces neuronal toxicity

Bulk RNA sequencing

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. SOURCE: Gregory,K,Tharp ( - Genomics Core Yerkes National Primate Research Center

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