Switchable DNA-Scaffolded Multivalent Aptamer through Stimuli-Responsive Plug-and-Play Modules for Protein Regulation

Area of Science:

• Biomolecular Engineering
• Synthetic Biology
• Nanotechnology

Background:

• Multivalent molecular interactions are crucial for biological functions, driving interest in multivalent materials for biosensing and medicine.
• Reversible switching between low-valency and multivalency is essential for functional regulation but challenging to achieve with multiple stimuli.
• Existing designs struggle to integrate multi-stimuli responsiveness for dynamic valency switching within a single system.

Purpose of the Study:

• To demonstrate a novel switchable multivalent system for dynamic regulation of thrombin activity.
• To introduce stimuli-responsive modules for plug-and-play switching in a DNA aptamer system.
• To explore multi-stimuli responsiveness for precise control over molecular interactions.

Main Methods:

• Constructed a multivalent system using thrombin aptamer-decorated DNA tile assembly.
• Integrated plug-and-play modules responsive to UV light, APE1, and RNase H as orthogonal switches.
• Developed three-layer switching cascades activated by one, two, or three stimuli to modulate thrombin activity.

Main Results:

• Successfully demonstrated a switchable multivalent system capable of reversible valency control.
• Achieved dynamic regulation of thrombin activity through stimuli-responsive DNA tile assembly.
• Engineered multi-stimuli responsive cascades and a tristate circuit for complex control logic.

Conclusions:

• The developed switchable DNA scaffold provides a versatile, modular platform for programmable multivalent regulation.
• This approach enables precise control over molecular interactions and biological activity.
• Potential applications include precision medicine, advanced biosensing, and novel biomaterials.