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Engineering of photo-inducible binary interaction tools for biomedical applications.
Yi-Tsang Lee1, Lei Guo2,3, Tien-Hung Lan1
1Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.
Nature Communications
|July 28, 2025
Summary
Researchers developed two photo-inducible binary interaction tools (PhoBITs) for optogenetic control. These systems enable precise manipulation of protein interactions and cellular functions, with potential therapeutic applications in cancer.
Area of Science:
- Synthetic Biology
- Optogenetics
- Molecular Biology
Background:
- The bacterial ssrA-sspB system offers a small peptide for protein manipulation.
- Existing optical dimerizers often use complex caging strategies.
Purpose of the Study:
- To develop novel photo-inducible binary interaction tools (PhoBITs) for optogenetic control.
- To create both light-ON and light-OFF systems for versatile protein interaction modulation.
Main Methods:
- Engineered PhoBIT1 by integrating LOV2 into sspB for a light-OFF switch.
- Developed PhoBIT2 using an evolved ssrA/CRY2-sspB pair for a light-ON switch with low basal interaction.
- Applied PhoBITs to study GPCRs, ion channels, necroptosis, and innate immune signaling.
- Utilized PhoBIT2 in a monobody to inhibit an oncogenic fusion protein in vivo.
Main Results:
- Demonstrated PhoBIT1 as a light-OFF switch and PhoBIT2 as a light-ON switch.
- Successfully modulated various signaling pathways and cellular processes.
- Showcased in vivo therapeutic potential by inhibiting leukemogenesis.
Conclusions:
- PhoBITs provide versatile, light-inducible control over protein interactions.
- These tools expand optogenetic engineering capabilities.
- PhoBITs hold promise for future therapeutic strategies.
