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. Author manuscript; available in PMC: 2023 Apr 14.
Published in final edited form as: Cell. 2022 Apr 14;185(8):1431–1443.e16. doi: 10.1016/j.cell.2022.03.023

Figure 1. Design of synthetic RIP receptors for customized antigen-dependent gene regulation in therapeutic cells.

Figure 1.

(A) Design of Synthetic Intramembrane Proteolysis Receptors. Receptors are comprised of a ligand binding domain (LBD), an extracellular domain (ECD), a transmembrane domain (TMD), a juxtamembrane domain (JMD), and a transcription factor (TF). Receptor circuits are designed to maximize clinical translation potential (B). A synRobo receptor replaces the Notch1 core with one from human Robo1. Compared to synNotch, a synRobo receptor fails to induce BFP. By replacing the TMD and JMD of Robo1 with those of Notch1, control of BFP production is lost. Deletion of a known ADAM10 cleavage site in the Robo1 ECD rescues ligand-dependent receptor behavior. (C) Same as B, but with minimal SNIPRs constructed using simple (GGS)n ECDs, and the TMD/JMD from Notch1. Statistics were calculated using unpaired T-tests, ***P≤0.001.