Synthetic GPCRs for programmable sensing and control of cell behaviour.

ABSTRACT: Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery and basic research^1,2. However, established technologies such as chimeric antigen receptors³ can only detect immobilized antigens, have limited output scope and lack built-in drug control^3-7. Here we engineer synthetic G-protein-coupled receptors (GPCRs) that are capable of driving a wide range of native or non-native cellular processes in response to a user-defined antigen. We achieve modular antigen gating by engineering and fusing a conditional auto-inhibitory domain onto GPCR scaffolds. Antigen binding to a fused nanobody relieves auto-inhibition and enables receptor activation by drug, thus generating programmable antigen-gated G-protein-coup

SUBMITTER: Kalogriopoulos NA 

PROVIDER: S-EPMC11666456 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature