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. Author manuscript; available in PMC: 2019 Jan 1.
Published in final edited form as: Cell. 2016 Oct 6;167(2):304–306. doi: 10.1016/j.cell.2016.09.033

Figure 1. Customized Sensing and Transcriptional Responses Using the synNotch Receptor in T Cells.

Figure 1.

(A) The synthetic Notch (synNotch) receptor is built upon a central core derived from the wild-type Notch receptor. This includes a transmembrane (TM) domain, two regulated proteolytic cleavage domains, and a series of Lin 12-Notch repeats and heterodimerization domains that prevent spontaneous receptor activation.

(B) Both the extra- and intra-cellular domains of Notch can be replaced in a synNotch receptor with diverse antigen recognition domains, such as the single-chain variable fragments (scFvs) of an antibody and an artificial transcription factor, such as Gal4-VP64.

(C and D) (C) In contrast with constitutive expression of transgenes using the 5’-long terminal repeat (LTR) of a retrovirus, (D) the synNotch receptor allows for customized therapeutic responses triggered in a ligand-dependent manner. This could include the release of specific cytokines, activation of lineage-specific transcription factors, triggering of defined effector mechanisms, or secretion of large macromolecules such as antibodies. CTLA4, cytotoxic T-lymphocyte associated protein 4; DR4, death receptor 4; PD1, programmed cell death 1; PEST, peptide sequence rich in proline, glutamate, serine, and threonine; UAS, upstream activation sequence.