Dear Editor,


The CRISPR system has been widely used for genome manipulation in various cells, tissues and whole organisms. Although an increasing variety of inducible CRISPR systems have been exploited for a variety of applications, such as chemical switch (Zetsche et al., 2015), photo switch(Shao et al., 2018) and solution ligand switch (Baeumler et al., 2017; Kipniss et al., 2017; Schwarz et al., 2017) systems, a cell-cell interaction inducible system is absent. The synthetic Notch (synNotch) receptor is a recently developed cell-cell contact sensing platform, which contains a customized extracellular sensor module, a transmembrane core domain of native Notch, and a customized intracellular responder module (Morsut et al.,

References

  • Adachi K, Kano Y, Nagai T, Okuyama N, Sakoda Y, Tamada K (2018) IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol 36:346–351

    Article  CAS  Google Scholar 

  • Baeumler TA, Ahmed AA, Fulga TA (2017) Engineering synthetic signaling pathways with programmable dCas9-based chimeric receptors. Cell Rep 20:2639–2653

    Article  CAS  Google Scholar 

  • He L, Huang J, Perrimon N (2017) Development of an optimized synthetic Notch receptor as an in vivo cell-cell contact sensor. Proc Natl Acad Sci U S A 114:5467–5472

    Article  CAS  Google Scholar 

  • James AC, Szot JO, Iyer K, Major JA, Pursglove SE, Chapman G, Dunwoodie SL (2014) Notch4 reveals a novel mechanism regulating Notch signal transduction. Biochim Biophys Acta 1843:1272–1284

    Article  CAS  Google Scholar 

  • Kipniss NH, Dingal P, Abbott TR, Gao Y, Wang H, Dominguez AA, Labanieh L, Qi LS (2017) Engineering cell sensing and responses using a GPCR-coupled CRISPR-Cas system. Nat Commun 8:2212

    Article  Google Scholar 

  • Morsut L, Roybal KT, **ong X, Gordley RM, Coyle SM, Thomson M, Lim WA (2016) Engineering customized cell sensing and response behaviors using synthetic Notch receptors. Cell 164:780–791

    Article  CAS  Google Scholar 

  • Rosenberg SA (2014) IL-2: the first effective immunotherapy for human cancer. J Immunol 192:5451–5458

    Article  CAS  Google Scholar 

  • Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA, Park JS, Lim WA (2016a) Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell 164:770–779

    Article  CAS  Google Scholar 

  • Roybal KT, Williams JZ, Morsut L, Rupp LJ, Kolinko I, Choe JH, Walker WJ, McNally KA, Lim WA (2016b) Engineering T cells with customized therapeutic response programs using synthetic Notch receptors. Cell 167(419–432):e416

    Google Scholar 

  • Sakamoto K, Chao WS, Katsube K, Yamaguchi A (2005) Distinct roles of EGF repeats for the Notch signaling system. Exp Cell Res 302:281–291

    Article  CAS  Google Scholar 

  • Schwarz KA, Daringer NM, Dolberg TB, Leonard JN (2017) Rewiring human cellular input-output using modular extracellular sensors. Nat Chem Biol 13:202–209

    Article  CAS  Google Scholar 

  • Shao J, Wang M, Yu G, Zhu S, Yu Y, Heng BC, Wu J, Ye H (2018) Synthetic far-red light-mediated CRISPR-dCas9 device for inducing functional neuronal differentiation. Proc Natl Acad Sci USA 115:E6722–E6730

    Article  CAS  Google Scholar 

  • Suzuki K, Tsunekawa Y, Hernandezbenitez R, Wu J, Jie Z, Kim EJ, Hatanaka F, Yamamoto M, Araoka T, Zhe L (2016) In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature 540:144–149

    Article  CAS  Google Scholar 

  • Weiskopf K, Ring AM, Ho CC, Volkmer JP, Levin AM, Volkmer AK, Ozkan E, Fernhoff NB, van de Rijn M, Weissman IL et al (2013) Engineered SIRPalpha variants as immunotherapeutic adjuvants to anticancer antibodies. Science 341:88–91

    Article  CAS  Google Scholar 

  • Zetsche B, Volz SE, Zhang F (2015) A split-Cas9 architecture for inducible genome editing and transcription modulation. Nat Biotechnol 33:139–142

    Article  CAS  Google Scholar 

Download references

FOOTNOTES

We are grateful to all members of the Lin and Rong labs for helpful comments and discussions on the manuscript. This work was supported by the National Natural Science Foundation of China (81670093 and 81872511), National Science and Technology Major Project (2018ZX10301101), Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110105005), the Program of Department of Science and Technology of Guangdong Province (2014B020212018), the Natural Science Foundation of Guangdong Province (2017A030310331 and 2018A030313455).

Hongxin Huang, **n Zhang, Jie Lv, Hongcheng Yang, **nlong Wang, Shufeng Ma, Ruoyang Shao, **n Peng, Ying Lin, and Zhili Rong declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by the any of the authors.

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Huang, H., Zhang, X., Lv, J. et al. Cell-cell contact-induced gene editing/activation in mammalian cells using a synNotch-CRISPR/Cas9 system. Protein Cell 11, 299–303 (2020). https://doi.org/10.1007/s13238-020-00690-1

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