Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors
By Leonardo Morsut, Kole T. Roybal, X. Xiong, R. Gordley, S. Coyle, M. Thomson, Wendell A. Lim. Cell, 2016
907 citations recorded by the source corpus.
The Notch protein is one of the most mechanistically direct transmembrane receptors – the intracellular domain contains a transcriptional regulator that is released from the membrane when engagement of the cognate extracellular ligand induces intramembrane proteolysis. We find that chimeric forms of Notch, in which both the extracellular sensor module and the intracellular transcriptional module are replaced with heterologous protein domains, can serve as a general platform for generating novel cell-cell contact signaling pathways. Synthetic Notch (synNotch) pathways can drive user-defined functional responses in diverse mammalian cell types. Because individual synNotch pathways do not share common signaling intermediates, the pathways are functionally orthogonal. Thus multiple synNotch receptors can be used in the same cell to achieve combinatorial integration of environmental cues, including Boolean response programs, multi-cellular signaling cascades, and self-organized cellular patterns. SynNotch receptors provide extraordinary flexibility in engineering cells with customized sensing/response behaviors to user-specified extracellular cues.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/b15746971a2e92d4c866da05b0c40027e86b93de
How researchers see this paper
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In Molecular Biology
In Oncology
- Wendell A. Lim
- C. June
- Whitney J. Walker
- Jasper Z. Williams
- Isabel Kolinko
- Joseph H. Choe
- Leonardo Morsut
- Krista A. McNally
Citations in the corpus
- Precision Tumor Recognition by T Cells With Combinatorial Antigen Sensing Circuits (2016, positive): “Recently, we have developed a new class of modular receptors called synthetic Notch (synNotch) receptors (Morsut et al., 2016 [this issue of Cell]).”
- The Principles of Engineering Immune Cells to Treat Cancer (2017, methodology): “This kind of priming function can be executed by using the recently developed synthetic Notch receptor (Morsut et al., 2016; Roybal (A–”
- Engineering T cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors (2016, positive): “To build a synNotch receptor platform that allows for fully customizable receptor sensing and transcriptional regulation, we utilized the Notch core regulatory region that controls ligand-dependent cleavage and activation as a minimal scaffold, but then append a customized input recognition (extrace”