Compositions, systems, and methods for allele-specific prime editing
A prime editing strategy using Cas9 nickase and reverse transcriptase selectively targets disease-associated rhodopsin alleles, addressing the limitations of current CRISPR/Cas9 methods by silencing mutations while preserving wild-type alleles, enhancing treatment efficacy for inherited retinal disorders.
Patent Information
- Application Number
- PCT/US2025/033042
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-06-10
- Filing Date
- 2025-06-10
- Publication Date
- 2025-12-18
AI Technical Summary
Current therapeutic approaches for inherited retinal disorders, particularly those affecting the rhodopsin gene, are limited by high development costs and lack of treatments for rare mutations, with existing CRISPR/Cas9 methods causing double-strand breaks and affecting wild-type alleles.
An allele-targeting, mutation-agnostic prime editing strategy using Cas9 nickase and reverse transcriptase to selectively silence disease-associated rhodopsin alleles by mutating or deleting the start codon, while preserving wild-type alleles, leveraging the rs7984 SNP for specificity.
The strategy effectively increases rod responses and thickens the outer nuclear layer in mouse models, demonstrating potential for broad treatment of inherited retinal diseases by targeting high-frequency SNPs without affecting wild-type alleles.