Engineering bi-directional chemically-modulated synthetic condensates for cellular control

作者：Ni Zhen, Yue Yan, Guangya Zhu, Tianxin Zhu, Qi Zhang, Qi Chen, Yan Guo, Jidong Zhu, Qiuhui Pan, Jingjing Xie · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-61877-w · 被引用次数：3 · 研究领域：RNA Research and Splicing、14-3-3 protein interactions、Chemical Synthesis and Analysis

Biomolecular condensates are membraneless compartments involved in a wide range of cellular processes. Despite their fundamental role in the spatiotemporal regulation of cellular functions, tools for precisely manipulating phase-separated condensates remain limited, and effective methods for discovering and functionalizing tunable phase separation modules from natural proteins are lacking. Here we present a rational engineering approach for androgen receptor (AR) and its clinically used drugs to create a chemical genetic platform, ARDrop, enabling condensates formation and dissolution. This platform is applied to a diverse set of proteins to achieve intended cellular functions, ensuring robust and long-lasting functionality through stable liquid-like properties. Our work develops a powerful toolkit for reversible manipulation of condensates that can be used for dissection of complicated cell signaling, laying the foundation for engineering designer condensates for synthetic biology applications. Tools for precisely manipulating phase-separated condensates remain limited. Here authors present an engineered system based on the androgen receptor, where clinically used drugs can be used to control the formation and dissolution of synthetic condensates, subsequently allowing control over various cellular processes.