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

Author

Listed:
  • Ni Zhen

    (Shanghai Jiao Tong University School of Medicine
    Lingang Laboratory)

  • Yue Yan

    (ShanghaiTech University
    Etern Biopharma)

  • Guangya Zhu

    (Lingang Laboratory)

  • Tianxin Zhu

    (Lingang Laboratory)

  • Qi Zhang

    (Shanghai Jiao Tong University School of Medicine
    Lingang Laboratory)

  • Qi Chen

    (Lingang Laboratory)

  • Yan Guo

    (Lingang Laboratory)

  • Jidong Zhu

    (Etern Biopharma
    Tianjin Medical University)

  • Qiuhui Pan

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine
    Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics
    Sanya Women and Children’s Hospital Managed by Shanghai Children’s Medical Center)

  • Jingjing Xie

    (ShanghaiTech University)

Abstract

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.

Suggested Citation

  • Ni Zhen & Yue Yan & Guangya Zhu & Tianxin Zhu & Qi Zhang & Qi Chen & Yan Guo & Jidong Zhu & Qiuhui Pan & Jingjing Xie, 2025. "Engineering bi-directional chemically-modulated synthetic condensates for cellular control," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61877-w
    DOI: 10.1038/s41467-025-61877-w
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