Interfering polypeptides targeting rex04 liquid-liquid phase separation and applications thereof

By designing interfering peptides that target the liquid-liquid phase separation of the REXO4 protein, and specifically binding to the N-terminal disordered domain of the REXO4 protein, the off-target effects and stability problems of existing radiosensitizers were solved, and the radiosensitization effect of tumor cells was achieved.

CN122145583APending Publication Date: 2026-06-05ZHENGZHOU UNIV +1

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
ZHENGZHOU UNIV
Filing Date
2026-02-12
Publication Date
2026-06-05

AI Technical Summary

Technical Problem

Existing radiosensitizers have problems such as strong off-target effects, short in vivo half-life, or large toxic side effects when targeting downstream enzymes of DNA damage repair-related signaling pathways. They cannot effectively target REXO4 protein liquid-liquid phase separation, leading to tumor radiotherapy resistance.

Method used

Design interference peptides that target the liquid-liquid phase separation of the REXO4 protein. These peptides interfere with the liquid-liquid phase separation by specifically binding to the N-terminal disordered domain of the REXO4 protein. The interference peptides include targeting peptides and cell-penetrating peptides, preferably using D-type amino acids to ensure stability in vivo and intracellular delivery.

Benefits of technology

It significantly reduces the efficiency of DNA damage repair in tumor cells, enhances the sensitivity of tumor cells to ionizing radiation, overcomes radiotherapy resistance, achieves radiosensitization, and improves the stability and anti-enzymatic ability of peptides in vivo.

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Abstract

The present application belongs to the technical field of biological medicine, and particularly relates to a kind of targeting REXO4 liquid-liquid phase separation interference polypeptide and its application.The interference polypeptide of the present application includes targeting peptide, the targeting peptide is specifically combined with REXO4 protein liquid-liquid phase separation driving domain, and the liquid-liquid phase separation of REXO4 protein is interfered;Wherein, the REXO4 protein liquid-liquid phase separation driving domain is REXO4 protein N-terminal disordered domain, and the amino acid sequence of the REXO4 protein N-terminal disordered domain is shown as sequence 1.The interference polypeptide of the present application can be specifically combined with REXO4 protein liquid-liquid phase separation driving domain, interfere with and destroy the functional LLPS of REXO4, cause the DNA damage repair efficiency in tumor cell to be significantly reduced, lead to the DNA break caused by ionizing radiation cannot be repaired in time, finally enhance the sensitivity of tumor cell to ionizing radiation, realize the effect of radiotherapy sensitization.
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