Cas9-Modulating Compound for Higher CRISPR Editing Specificity

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Solution Overview

Problem

The accuracy of CRISPR-Cas9 gene editing is not satisfying, necessitating the development of compounds to regulate its efficiency and improve specificity.

Innovation Solution

A compound represented by Formula I, or its pharmaceutically acceptable salts, optical isomers, or solvates, is used to inhibit or enhance the specificity of gene editing, particularly through the CRISPR/Cas9 system, by reducing off-target effects and inhibiting DNA repair mechanisms like NHEJ and HDR.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If CRISPR-Cas9 system is used for gene editing, then gene editing efficiency is improved, but gene editing specificity deteriorates

Engineering Contradiction:

Improvegene editing efficiencyVSAvoidgene editing specificity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent introduces small molecule compounds as intermediaries that specifically bind to the Cas9 protein to modulate its activity. These compounds act as mediators between the CRISPR-Cas9 system and the target DNA, enhancing on-target editing while suppressing off-target effects through allosteric modulation of Cas9

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs small molecule compounds that alter the functional parameters of the Cas9 protein by binding to specific pockets on the protein structure. This changes the conformational state and catalytic activity of Cas9, thereby improving editing specificity without sacrificing efficiency

Inventive Principle:

Principle #35Parameter changes

2Manufacturing precision

If small molecule compounds are used to inhibit Cas9, then gene editing specificity is improved, but gene editing efficiency deteriorates

Engineering Contradiction:

Improvegene editing specificityVSAvoidgene editing efficiency

Core Design Contradiction:

Manufacturing precisionVSProductivity

Solution Approach 1:

The patent uses small molecule compounds that partially modulate Cas9 activity rather than completely inhibiting it. This partial action allows sufficient on-target editing to occur while selectively suppressing off-target effects, achieving a balance between specificity and efficiency

Inventive Principle:

Principle #16Partial or excessive action

Data Source

PatentUS12534742B2Compound for regulating gene editing efficiency and application thereof

Publication Date: 2026.01.27 SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI

AI summary

A compound for improving the gene editing specificity and application thereof. Specifically disclosed is a compound represented by formula I or a use of a pharmaceutically acceptable salt thereof. The compound and the pharmaceutically acceptable salt thereof are used for preparing an inhibitor, a composition, or a formulation for inhibiting gene editing and/or improving the gene editing specificity. The structure of the formula I is as stated in the description. The compound can significantly improve the accuracy of CRISPR gene editing, thereby providing a simple and high-efficient policy for accurate gene editing.