Synthetic Intramembrane Proteolysis Receptor (SNIPR)

Synthetic intramembrane proteolysis receptors (SNIPRs) are engineered, modular cell-surface receptors designed to enable precise and programmable control of cellular responses. They function by coupling extracellular ligand recognition to the release of an intracellular transcription factor via regulated intramembrane proteolysis, thereby activating specific genetic programs in response to defined external signals. SNIPRs are composed of an extracellular ligand-binding domain, a transmembrane core, and an intracellular effector domain. Upon ligand binding, the receptor undergoes conformational changes that expose a cleavage site within the transmembrane region, leading to protease-mediated cleavage and release of the transcription factor.

Ligand-induced intramembrane proteolysis leading to transcription factor release and target gene expression.