Self-assembled cGAMP-STINGΔTM signaling complex as a bioinspired platform for cGAMP delivery
Author(s)
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; ... Show more Show less
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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.
Date issued
2020-06Department
Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and EngineeringJournal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Citation
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).
Version: Final published version
ISSN
2375-2548