Conversion of natural cytokine receptors into orthogonal synthetic biosensors.

ABSTRACT: Synthetic receptors enable bioengineers to build cell-based therapies that perform therapeutic functions in a targeted or conditional fashion to enhance specificity and efficacy. Although many synthetic receptors exist, it remains challenging to generate new receptors that sense soluble cues and relay that detection through orthogonal mechanisms independent of native pathways. Here we co-opt natural cytokine receptor ectodomains into modular extracellular sensor architecture (MESA) receptors to form natural ectodomain (NatE) MESA receptors. We generated multiple functional, orthogonal synthetic cytokine receptors, identified design principles and constraints and propose guidance for extending this approach to other natural receptors. We demonstrate the utility of NatE MESA by engineering T

SUBMITTER: Edelstein HI 

PROVIDER: S-EPMC12380174 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature