Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). The stimulator of interferon (IFN) genes (STI...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/133091 |
| _version_ | 1826207688382480384 |
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| author | He, Yanpu Hong, Celestine Yan, Emily Z Fletcher, Samantha J Zhu, Ge Yang, Mengdi Li, Yingzhong Sun, Xin Irvine, Darrell J Li, Jiahe Hammond, Paula T |
| author_facet | He, Yanpu Hong, Celestine Yan, Emily Z Fletcher, Samantha J Zhu, Ge Yang, Mengdi Li, Yingzhong Sun, Xin Irvine, Darrell J Li, Jiahe Hammond, Paula T |
| author_sort | He, Yanpu |
| collection | MIT |
| description | Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). The stimulator of interferon (IFN) genes (STING) pathway constitutes a highly important part of immune responses against various cancers and infections. Consequently, administration of STING agonists such as cyclic GMP-AMP (cGAMP) has been identified as a promising approach to target these diseases. In cancer cells, STING signaling is frequently impaired by epigenetic silencing of STING; hence, conventional delivery of only its agonist cGAMP may be insufficient to trigger STING signaling. In this work, while expression of STING lacking the transmembrane (TM) domain is known to be unresponsive to STING agonists and is dominant negative when coexpressed with the full-length STING inside cells, we observed that the recombinant TM-deficient STING protein complexed with cGAMP could effectively trigger STING signaling when delivered in vitro and in vivo, including in STING-deficient cell lines. Thus, this bioinspired method using TM-deficient STING may present a universally applicable platform for cGAMP delivery. |
| first_indexed | 2024-09-23T13:53:42Z |
| format | Article |
| id | mit-1721.1/133091 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:53:42Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1330912021-10-27T20:25:26Z Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery He, Yanpu Hong, Celestine Yan, Emily Z Fletcher, Samantha J Zhu, Ge Yang, Mengdi Li, Yingzhong Sun, Xin Irvine, Darrell J Li, Jiahe Hammond, Paula T Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). The stimulator of interferon (IFN) genes (STING) pathway constitutes a highly important part of immune responses against various cancers and infections. Consequently, administration of STING agonists such as cyclic GMP-AMP (cGAMP) has been identified as a promising approach to target these diseases. In cancer cells, STING signaling is frequently impaired by epigenetic silencing of STING; hence, conventional delivery of only its agonist cGAMP may be insufficient to trigger STING signaling. In this work, while expression of STING lacking the transmembrane (TM) domain is known to be unresponsive to STING agonists and is dominant negative when coexpressed with the full-length STING inside cells, we observed that the recombinant TM-deficient STING protein complexed with cGAMP could effectively trigger STING signaling when delivered in vitro and in vivo, including in STING-deficient cell lines. Thus, this bioinspired method using TM-deficient STING may present a universally applicable platform for cGAMP delivery. 2021-10-25T16:37:40Z 2021-10-25T16:37:40Z 2020 2021-06-10T15:37:54Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133091 He, Yanpu, Hong, Celestine, Yan, Emily Z, Fletcher, Samantha J, Zhu, Ge et al. 2020. "Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery." Science Advances, 6 (24). en 10.1126/SCIADV.ABA7589 Science Advances Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf American Association for the Advancement of Science (AAAS) Science Advances |
| spellingShingle | He, Yanpu Hong, Celestine Yan, Emily Z Fletcher, Samantha J Zhu, Ge Yang, Mengdi Li, Yingzhong Sun, Xin Irvine, Darrell J Li, Jiahe Hammond, Paula T Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery |
| title | Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery |
| title_full | Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery |
| title_fullStr | Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery |
| title_full_unstemmed | Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery |
| title_short | Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery |
| title_sort | self assembled cgamp stingδtm signaling complex as a bioinspired platform for cgamp delivery |
| url | https://hdl.handle.net/1721.1/133091 |
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