Researchers at the University of Washington reported a platform for engineering therapeutic proteins that incorporate logical decision‑making to restrict activity to desired tissues. These programmable proteins evaluate molecular inputs and activate only under specific combinations of local signals, minimizing off‑target exposure. The engineered molecules use modular sensing domains and programmable logic circuits to couple target recognition with downstream therapeutic functions—an approach analogous to electronic logic gates but implemented in protein architecture. The team demonstrated targeted activation in preclinical models, showing reduced systemic toxicity and improved on‑target potency. This advance offers a new design paradigm for tissue‑selective biologics and immunotherapies by enabling autonomous site‑specific action without relying solely on delivery vehicles or systemic dosing changes.