From Caffeine to Aspirin: Everyday Molecules as Triggers for Genetically Encoded Proximity Systems
Mingguang Cui1, Tianlu Wang1, Yaoyu Han1
1Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas, USA.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|August 4, 2026
Summary
Chemically induced proximity (CIP) systems can be improved using familiar dietary molecules and OTC drugs. This approach enhances safety and therapeutic potential for precise biological control.
Area of Science:
- Biotechnology
- Molecular Biology
- Synthetic Biology
Background:
- Chemically induced proximity (CIP) offers programmable control over biological processes using small molecules.
- Traditional CIP platforms face limitations in therapeutic translation due to safety, off-target effects, and immunogenicity concerns.
Purpose of the Study:
- To highlight dietary small molecule- and OTC drug-responsive CIP systems as safer alternatives for translational chemogenetic control.
- To explore novel design strategies for developing clinically compatible proximity-control systems.
Main Methods:
- Exploiting nanobody-derived binders against familiar small molecules (e.g., synthetic anti-caffeine nanobody systems).
- Adapting naturally evolved ligand-binding proteins via rational protein engineering (e.g., salicylate-responsive platforms).
Main Results:
- Demonstrated transformation of familiar molecules (caffeine, salicylic acid, aspirin) into programmable biological inputs.
- Developed salicylate- and aspirin-responsive platforms for reversible proximity control and gene regulation.
Conclusions:
- Dietary small molecule- and OTC drug-responsive CIP systems offer a promising avenue for safer and more translatable chemogenetic control.
- AI-guided protein engineering can further expand the design space for novel ligand-responsive modules, enhancing clinical compatibility.
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