Engineered gene transcription repressional tool targeting inhibin subunit βe (INHBE) and use thereof

By designing a complex containing DNA methylation and transcriptional repressor domains, which specifically binds to the INHBE gene regulatory element, the unknowns and limitations of existing tools are overcome, achieving efficient silencing regulation of the INHBE gene, reducing the risk of obesity-related diseases and muscle atrophy, and providing a well-tolerated obesity treatment option.

WO2025261474A1 Publication Date: 2025-12-26EPIGENIC THERAPEUTICS INC
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Patent Information

Application Number
PCT/CN2025/102298
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-06-21
Filing Date
2025-06-20
Publication Date
2025-12-26

AI Technical Summary

Technical Problem

Existing epigenetic editing tools targeting the INHBE gene have not been able to effectively and sustainably suppress its expression, and there are unknowns and limitations. This leads to side effects such as weight rebound and muscle atrophy in obesity treatment, and GLP-1 receptor agonists have poor tolerability after long-term use.

Method used

Design a complex comprising a DNA methylation domain and a transcriptional repressor domain to specifically bind to the transcriptional regulatory elements of the INHBE gene. Utilize the interaction between the nucleic acid binding domain and the recruitment domain to achieve silencing regulation of the INHBE gene, avoiding the risks of DNA cleavage and immunogenicity.

Benefits of technology

It achieves efficient silencing regulation of the INHBE gene, significantly reduces the risk of obesity-related diseases, provides long-term weight control, and avoids muscle loss and tolerance issues.

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Abstract

The present application relates to an engineered gene transcriptional repression tool targeting inhibin subunit βE (INHBE) and the use thereof, and specifically relates to a complex comprising a first fusion and a second fusion, wherein: 1) one of the first fusion and the second fusion comprises a DNA methylation domain and at least one recruitment domain A, and the other fusion comprises a transcriptional repressor domain and at least one recruitment domain A'; and 2) the first fusion or the second fusion comprises a nucleic acid-binding domain. Moreover, the recruitment domain A and the recruitment domain A' are capable of interacting with each other, such that one of the first fusion and the second fusion or a part thereof can be recruited to the vicinity of the other fusion; and the nucleic acid-binding domain is capable of specifically binding to an INHBE gene transcriptional regulatory element.
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