Treatment of autosomal dominant retinitis pigmentosa caused by RHO-P23H mutation with high-fidelity Cas13X in mice.

ABSTRACT: Mutations in Rhodopsin (RHO) gene commonly cause autosomal dominant retinitis pigmentosa (adRP) without effective therapeutic treatment so far. Compared with genomic DNA-targeting CRISPR-Cas9 system, Cas13 edits RNA for therapeutic applications, avoiding the risk of causing permanent changes in the genome. In particular, a compact and high-fidelity Cas13X (hfCas13X) recently has been developed to degrade targeted RNA with minimal collateral effects and could also be packaged in a single adeno-associated virus for efficient in vivo delivery. In this study, we engineered single-guide RNA for hfCas13X to specifically knock down human mutant Rhodopsin transcripts RHO-P23H with minimal effect on wild-type transcripts. Moreover, treatment with hfCas13X alleviated the adRP pr

SUBMITTER: Yan Z 

PROVIDER: S-EPMC10445100 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature