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Boolean Logic-Based Controlled Release of Bioactive Proteins with Diversified Inputs.

Murial L Ross1, Ryan Gharios2, Shivani Kottantharayil1

  • 1Department of Bioengineering, University of Washington, Seattle, WA, 98105, USA.

Angewandte Chemie (International Ed. in English)
|November 10, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed a new method using protein assembly to control the release of various bioactive proteins from biomaterials based on specific protease combinations or light signals. This advances logic-based control for applications like targeted drug delivery.

Keywords:
Bioactive therapeuticsBoolean logicDrug deliveryProtein engineeringStimuli‐responsive

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Area of Science:

  • Biomaterials Science
  • Molecular Engineering
  • Synthetic Biology

Background:

  • Stimuli-responsive biomaterials are crucial for controlled therapeutic delivery, tissue engineering, and biosensing.
  • Previous work utilized autonomous compilation for protein release from biomaterials based on Boolean logic, but was limited to simple outputs and inputs.
  • Expanding this framework is essential for broader applications in biomedicine.

Purpose of the Study:

  • To extend the capabilities of logic-based protein release from biomaterials.
  • To demonstrate the assembly of all seven unique logical operations using a 3-input operator set.
  • To enable the release of diverse bioactive proteins in response to specific stimuli.

Main Methods:

  • Assembled all 7 unique logical operations (YES/OR/AND) for protein release control.
  • Utilized three orthogonal protease actuators to trigger conditional release of protein cargos.
  • Incorporated a photocleavable protein motif to enable visible light as an additional release input.

Main Results:

  • Successfully demonstrated the programmable release of diverse bioactive proteins, including growth factors, enzymes, nanobodies, cytokines, and fluorescent proteins.
  • Achieved logic-based release from material anchors in response to precise combinations of protease inputs, maintaining protein bioactivity.
  • Showcased visible light as a controllable input for logic-based protein release.

Conclusions:

  • The developed framework significantly expands the applicability of logic-based protein release from biomaterials.
  • This approach enables precise control over the release of various functional biomacromolecules.
  • The findings pave the way for advanced applications in targeted therapeutics, diagnostics, and synthetic biology.