开发具有无可检测的脱靶效应的双gRNA方法以纠正C9ORF72重复扩增和C9ORF72病理学
By designing a dual gRNA genome to remove repetitive DNA in the C9ORF72 genome and using the CRISPR/Cas9 system for gene editing, the toxicity issues at the DNA, RNA, and protein levels caused by C9ORF72 repetitive amplification were resolved, achieving a highly effective treatment with no off-target effects and demonstrating the potential to treat ALS and FTD.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- TSINGHUA UNIVERSITY
- Filing Date
- 2019-12-23
- Publication Date
- 2026-07-17
AI Technical Summary
Currently, there is no effective treatment that can simultaneously target the DNA, RNA, and protein toxicity caused by C9ORF72 repeat amplification, making the pathogenesis of ALS and FTD diseases complex and difficult to treat.
A dual gRNA-mediated deletion method was employed to design a specific gRNA genome to remove repetitive DNA in the C9ORF72 genome. Gene editing was performed using the CRISPR/Cas9 system, combined with a genome-wide off-target detector to ensure undetectable off-target effects, achieving efficient removal of repetitive DNA and correction of RNA and protein abnormalities.
This method efficiently removes C9ORF72 repetitive DNA in vitro and in vivo, significantly reduces RNA clusters, and has almost no impact on C9ORF72 protein expression, providing a highly effective and permanent treatment option with potential value in treating ALS and FTD.
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