A phase separation-fortified bi-specific adaptor for conditional tumor killing  

作　　者：Yuyan Liu Yuting Zhu Weifan Xu Pilong Li 

机构地区：[1]State Key Laboratory of Membrane Biology,Frontier Research Center for Biological Structure,Tsinghua University-Peking University Joint Center for Life Sciences,School of Life Sciences,Tsinghua University,Beijing 100084,China

出　　处：《Science China(Life Sciences)》2024年第7期1385-1397,共13页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(32150023)。

摘　　要：A common approach in therapeutic protein development involves employing synthetic ligands with multivalency,enabling sophisticated control of signal transduction.Leveraging the emerging concept of liquid-liquid phase separation(LLPS)and its ability to organize cell surface receptors into functional compartments,we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways,thus inducing the rapid,potent,and specific apoptosis of tumor cells.Despite their simplicity,these“triggers”,named phase-separated Tumor Killers(hereafter referred to as psTK),are sufficient to yield interreceptor clustering of death receptors(represented by DR5)and tumor-associated receptors,with notable features:LLPSmediated robust high-order organization,well-choreographed conditional activation,and broad-spectrum capacity to potently induce apoptosis in tumor cells.The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction.This approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

关 键 词：phase separation therapeutic proteins receptor-ligand interactions DR5 tumor apoptosis 

分 类 号：R73-36[医药卫生—肿瘤]