Engineering advanced logic and distributed computing in human CAR immune cells
© 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/136156 |
| _version_ | 1826191524935761920 |
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| author | Cho, Jang Hwan Okuma, Atsushi Sofjan, Katri Lee, Seunghee Collins, James J Wong, Wilson W |
| author_facet | Cho, Jang Hwan Okuma, Atsushi Sofjan, Katri Lee, Seunghee Collins, James J Wong, Wilson W |
| author_sort | Cho, Jang Hwan |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T08:57:13Z |
| format | Article |
| id | mit-1721.1/136156 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:57:13Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1361562021-10-28T04:50:55Z Engineering advanced logic and distributed computing in human CAR immune cells Cho, Jang Hwan Okuma, Atsushi Sofjan, Katri Lee, Seunghee Collins, James J Wong, Wilson W © 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. 2021-10-27T20:31:08Z 2021-10-27T20:31:08Z 2021 2021-08-25T17:57:09Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136156 en 10.1038/S41467-021-21078-7 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Cho, Jang Hwan Okuma, Atsushi Sofjan, Katri Lee, Seunghee Collins, James J Wong, Wilson W Engineering advanced logic and distributed computing in human CAR immune cells |
| title | Engineering advanced logic and distributed computing in human CAR immune cells |
| title_full | Engineering advanced logic and distributed computing in human CAR immune cells |
| title_fullStr | Engineering advanced logic and distributed computing in human CAR immune cells |
| title_full_unstemmed | Engineering advanced logic and distributed computing in human CAR immune cells |
| title_short | Engineering advanced logic and distributed computing in human CAR immune cells |
| title_sort | engineering advanced logic and distributed computing in human car immune cells |
| url | https://hdl.handle.net/1721.1/136156 |
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