Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality

Hojun Choi, Youngeun Kim, Amin Mirzaaghasi, Jaenyoung Heo, Yu Na Kim, Ju Hye Shin, Seonghun Kim, Nam Hee Kim, Eunae Sandra Cho, Jong In Yook, Tae Hyun Yoo, Eunjoo Song, Pilhan Kim, Eui Cheol Shin, Kyungsoo Chung, Kyungsun Choi, Chulhee Choi

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes. We showed that intraperitoneal injection of purified srIκB-loaded exosomes (Exo-srIκBs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srIκBs were observed mainly in the neutrophils, and in monocytes to a lesser extent, in the spleens and livers of mice. Moreover, we found that Exo-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.

Original languageEnglish
Article numbereaaz6980
JournalScience Advances
Volume6
Issue number15
DOIs
Publication statusPublished - 2020

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (NRF- 2017R1D1A1B03034177) and a faculty research grant of Yonsei University College of Medicine (6-2019-0078).

Publisher Copyright:
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).

All Science Journal Classification (ASJC) codes

  • General

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