Cell-cell contact-induced gene editing/activation in mammalian cells using a synNotch-CRISPR/Cas9 system
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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.,2016).Because of its extraordinary flexibility in terms of customizable sensing/response behaviors,the synNotch receptor serves as a powerful tool for cell engineering (Roybal et al.,2016a;Roybal et al.,2016b;He et al.,2017).In the current study,we combined the synNotch receptor with the CRISPR/Cas9 system to develop a cell-cell interaction inducible gene regulated tool.
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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 ;National Science and Technology Major Project ;Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory ;the Program of Department of Science and Technology of Guangdong Province ;the Natural Science Foundation of Guangdong Province