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Exosome-based Delivery of Super-Repressor IκBα Relieves Sepsis-Associated Organ Damage and Mortality

Authors
 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 
Citation
 SCIENCE ADVANCES, Vol.6(15) : eaaz6980, 2020-04 
Journal Title
 SCIENCE ADVANCES 
Issue Date
2020-04
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.
DOI
10.1126/sciadv.aaz6980
Appears in Collections:
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Jung, Kyung Soo(정경수) ORCID logo https://orcid.org/0000-0003-1604-8730
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/176071
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