Hormone-responsive synthetic condensates enable programmable gene control
Schematic representation of the regulation of gene switches by natural hormones or pharmacological agonists. The system allows for a quick response and simultaneous and independent operation through several different receptors.
Researchers of the Department of Synthetic Biology and Immunology have developed a new synthetic biology platform that repurposes human nuclear receptors to create ligand-controlled protein switches and liquid biomolecular condensates.
Led by Roman Jerala, the team engineered chemically induced dimerization systems based on nuclear receptor ligand-binding domains and coactivator peptides. These modules respond directly to physiological signals such as thyroid hormone, vitamin D, estrogen, retinoic acid, and cortisol.
Key achievements include:
- reversible ON/OFF transcriptional control using clinically relevant ligands,
- multi-input gene regulation,
- hormone-triggered liquid–liquid phase separation (LLPS),
- and transcriptional amplification exceeding 200-fold when combined with CRISPR/dCas9.
Unlike many existing systems that rely on foreign proteins or synthetic drugs, this approach is built entirely from human components, enabling tighter integration with endogenous signaling networks.
The work establishes a versatile toolkit for constructing responsive gene circuits, studying phase separation, and developing future therapeutic and biosensing applications.
Publication: https://www.nature.com/articles/s41467-026-69099-4