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Updated: Aug 6, 2026
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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
Chemically Responsive Protein Switches for the Precise Control of Biological Activities
Jaime Franco Pinto1, Naama Drahy1, Séverine Divoux2
1Sorbonne Université, École Normale Supérieure, Université PSL, CNRS, Chimie Physique et Chimie du Vivant (CPCV), 75005 Paris, France.
ACS Chemical Biology
|July 20, 2026
Summary
Researchers developed CATCHFIRE and CATCH-ON, novel chemical systems for reversible protein control. These technologies precisely regulate cellular functions and gene expression, offering new tools for research and therapy.
Area of Science:
- Molecular Biology
- Chemical Biology
- Biotechnology
Background:
- Controlling protein interactions with small molecules is key to regulating cellular functions.
- Existing methods for chemical control of biological processes can be limited in scope or reversibility.
Purpose of the Study:
- To develop a novel technology for chemically inducing protein dimerization and controlling biological activities.
- To create a chemically inducible gene expression system for precise regulation of cellular functions and protein secretion.
Main Methods:
- Leveraged CATCHFIRE (chemically assisted tethering of chimera by fluorogenic induced recognition) technology for reversible chemical induction of dimerization.
- Engineered CATCH-ON, a system utilizing chemically induced dimerization of GAL4 and p65Δ to control gene expression.
- Applied CATCH-ON to regulate expression of enzymes (proteases, DNA recombinases, suicide switches) and secretion of therapeutic proteins (insulin).
Main Results:
- CATCHFIRE enabled chemically induced assembly and function of split enzymes like luciferases, proteases, and DNA recombinases.
- CATCH-ON demonstrated precise, reversible, titratable, and nontoxic control over gene expression and protein secretion.
- The system proved compatible with other chemically induced dimerization systems.
Conclusions:
- CATCHFIRE and CATCH-ON provide powerful tools for reversible chemical control of protein interactions and biological functions.
- These systems offer precise regulation for applications in basic research, biotechnology, and cell therapy.
- The technology opens new avenues for developing advanced therapeutic strategies and research methodologies.
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