Engineering advanced logic and distributed computing in human CAR immune cells
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s41467-021-21078-7.pdf
Description
Published version
Size
2.18 MB
Format
Unknown
Checksum (MD5)
57bc3596e7b2fefd824d96c56ff5c12d
Author(s)
Cho, Jang Hwan
Okuma, Atsushi
Sofjan, Katri
Lee, Seunghee
Collins, James J.
Wong, Wilson W
Date Issued
2021
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2021, The Author(s). The immune system is a sophisticated network of different cell types performing complex biocomputation at single-cell and consortium levels. The ability to reprogram such an interconnected multicellular system holds enormous promise in treating various diseases, as exemplified by the use of chimeric antigen receptor (CAR) T cells as cancer therapy. However, most CAR designs lack computation features and cannot reprogram multiple immune cell types in a coordinated manner. Here, leveraging our split, universal, and programmable (SUPRA) CAR system, we develop an inhibitory feature, achieving a three-input logic, and demonstrate that this programmable system is functional in diverse adaptive and innate immune cells. We also create an inducible multi-cellular NIMPLY circuit, kill switch, and a synthetic intercellular communication channel. Our work highlights that a simple split CAR design can generate diverse and complex phenotypes and provide a foundation for engineering an immune cell consortium with user-defined functionalities.
MIT Department
Massachusetts Institute of Technology. Synthetic Biology Center
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41467-021-21078-7
