Inhibition of unintended mutations in gene editing

A nucleobase deaminase inhibitor system addresses the specificity issues of CRISPR/Cas-based base editors, enhancing precision in genome editing by minimizing off-target mutations and enabling effective therapeutic applications.

JP2026012727APending Publication Date: 2026-01-27SHANGHAI TECH UNIV
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Patent Information

Application Number
JP2025170065
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2019-02-02
Filing Date
2025-10-08
Publication Date
2026-01-27

AI Technical Summary

Technical Problem

Current genome editing tools, particularly CRISPR/Cas-based base editors, suffer from low specificity, leading to unintended mutations in single-stranded DNA regions, limiting their application in therapeutic contexts such as correcting T to C transitions associated with human diseases.

Method used

Development of a nucleobase deaminase inhibitor fused to a nucleobase deaminase via a protease cleavage site, allowing precise control over editing by inhibiting activity in off-target regions and enabling targeted base editing.

Benefits of technology

Enhances the specificity of base editing, reducing unintended mutations and facilitating clinical translation by ensuring accurate gene correction.

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Abstract

Provided are a fusion protein useful for performing base editing, a method for performing gene editing in a cell at a target site, a dual guide RNA system, and a guide RNA.SOLUTION: To provide fusion proteins and related molecules useful for performing base editing with reduced or no off-target mutations. The fusion protein can comprise a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems comprising prime editing guide RNAs with improved stability.SELECTED DRAWING: None
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