数字农科院2.0

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

文献类型： 外文期刊

作者： Zixiang Yan;Yuqin Yao;Luyao Li;Lingqiong Cai;Haiwei Zhang;Shenghai Zhang;Qingquan Xiao;Xing Wang;Erwei Zuo;Chunlong Xu;Jihong Wu;Hui Yang

作者机构：

关键词： adRP;hfCas13X;MT: RNA/DNA editing;P23H mutation;retinitis pigmentosa;rhodopsin

期刊名称： Molecular Therapy - Nucleic Acids

ISSN： 2162-2531

年卷期： 2023 年 33 卷

页码：

收录情况： SCIE（2023版）

摘要： 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 progression in both RHO-P23H overexpression-induced and humanized hRHOP23H/WT mouse models. Our study indicates the potential of hfCas13X in treating adRP caused by RHO mutations and other genetic diseases.

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