Cell surface sculpting using logic-gated protein actuators.

Area of Science:

• Synthetic Biology
• Biotechnology
• Molecular Engineering

Background:

• Cellular surface markers exhibit heterogeneity, especially in pathological conditions, presenting challenges for targeted therapies.
• Existing immunotherapies and protein therapeutics aim to exploit cell surface differences but often lack specificity due to single-antigen limitations.
• There is a need for programmable molecular systems that integrate multiple cell surface features for precise cell targeting.

Approach:

• Developed an autonomous decision-making protein device utilizing proximity-gated protein trans-splicing.
• Demonstrated the platform's ability to locally generate an active protein from two inactive fragments upon specific cell surface input.
• Engineered the protein actuator to perform Boolean logic operations on cell surfaces.

Key Points:

• The protein device enables Boolean logic operations, allowing for complex decision-making based on cell surface marker combinations.
• Achieved highly selective recruitment of enzymatic and cytotoxic activities to specific cells within mixed populations.
• The platform's modularity and tunability support diverse inputs, targeting modalities, and functional outputs.

Conclusions:

• This proximity-gated protein trans-splicing technology offers a powerful tool for precise cell targeting and manipulation.
• The protein actuator platform has broad applications in synthetic biology and biotechnology for developing advanced therapeutics.
• Future development may lead to more sophisticated and personalized cell-based therapies.