M4di variant

By optimizing the hM4Di receptor through molecular biology and protein engineering, enhancing the sensitivity of exogenous ligands and prolonging the desensitization time, the problem of the lack of sustained therapeutic effect of hM4Di receptor in pain treatment was solved, achieving more effective long-term therapeutic effects and reducing side effects.

WO2026138951A1PCT designated stage Publication Date: 2026-07-02CHINESE INST FOR BRAIN RES BEIJING +1

Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
CHINESE INST FOR BRAIN RES BEIJING
Filing Date
2025-12-25
Publication Date
2026-07-02

AI Technical Summary

Technical Problem

The existing hM4Di receptor is limited in its ability to treat pain due to ligand sensitivity, response intensity, and desensitization time, resulting in inconsistent therapeutic effects. High doses of CNO may cause nonspecific effects, which limits the practicality and effectiveness of long-term treatment.

Method used

By optimizing the hM4Di receptor through molecular biology and protein engineering, we can enhance its sensitivity to exogenous ligands and prolong the desensitization time. By combining it with excitatory neuron-specific promoters, we can improve its targeting and inhibitory efficacy and reduce the risk of side effects.

Benefits of technology

It enables sustained therapeutic effects with lower doses of exogenous ligands, enhances targeting of specific neuronal subsets, reduces non-specific effects, and improves the long-term efficacy of chemogenetic therapy.

✦ Generated by Eureka AI based on patent content.

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Abstract

Provided is a modified human G protein-coupled receptor (GPCR), the modified GPCR having the following characteristics: (i) reduced reactivity to endogenous ligands compared to wild-type GPCR; and (ii) unchanged or enhanced reactivity to exogenous ligands compared to wild-type GPCR.
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