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.
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
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.
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.
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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