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US 2026/0053882 A1Published application
Logic gated protein actuators
AssigneeThe Trustees of Princeton University
InventorsThomas W. MUIR, Christian KOFOED, Gihoon LEE, Josef GRAMESPACHER, Nicholas TAY, Xuanjia YE, Girum ERKALO
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Abstract
A logic-gated protein device in which proximity-gated protein trans-splicing governs formation of an active protein from two otherwise inactive fragments.
Claims43
A logic-gated protein actuator system, comprising:
- a mixture comprising
- a first component comprising a first caged split intein fragment fused to a first protein-of-interest fragment and fused to a first antigen-binding domain configured to bind to a first surface antigen;
- and
- a second component comprising a second caged split intein fragment fused to a second protein-of-interest fragment and fused to a second antigen-binding domain configured to bind to a second surface antigen,
- wherein the first caged split intein fragment and the second caged split intein fragment are capable of undergoing protein trans-splicing to form a protein of interest from the first protein-of-interest fragment and the second protein-of-interest fragment when the first antigen-binding domain and the second antigen-binding domain are proximal, and
- wherein the first caged split intein fragment and the second caged split intein fragment are an actuator.
3 more elements
A method of conditionally forming a protein of interest, comprising:
- providing a mixture comprising
- a first component comprising a first caged split intein fragment fused to a first protein-of-interest fragment and fused to a first antigen-binding domain configured to bind to a first surface antigen;
- and
- a second component comprising a second caged split intein fragment fused to a second protein-of-interest fragment and fused to a second antigen-binding domain configured to bind to a second surface antigen,
- bringing the mixture into contact with a cell having a surface, and
- when the first surface antigen and the second surface antigen are proximal on the surface of the cell, allowing the first antigen-binding domain to bind to the first surface antigen and the second antigen-binding domain to bind to the second surface antigen, and allowing the first caged split intein fragment and the second caged split intein fragment to undergo protein trans-splicing to form a protein of interest from the first protein-of-interest fragment and the second protein-of-interest fragment,
- wherein the first caged split intein fragment and the second caged split intein fragment are an actuator.
4 more elements
Dependencies are inferred from the claim text.