Significant protective effect of engineered exosomes in animal models of sepsis

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 had been previously developed was implemented for loading a large amount of srIκB into exosomes. A team led by researchers at KAIST and ILIAS Biologics Inc. 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, the researchers found that Exo-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.

Generation and characterization of engineered exosomes


(A) Schematic of DNA constructs used for the production of Exo-srIκB (top). Schematic showing fusion proteins and their proposed activities (bottom). (B) Morphological characterization of Exo-Naïve and Exo-srIκB through transmission electron microscopy. (C) HEK293T cells that stably express mCherry or srIκB, and exosomes from these HEK293T cells, were lysed and immunoblotted against the indicated proteins. IB, immunoblot.

Choi H, Kim Y, Mirzaaghasi A, Heo J, Kim YN, Shin JH, Kim S, Kim NH, Cho ES, Yook JI, Yoo TH, Song E, Kim P, Shin EC, Chung K, Choi K, Choi C. (2020) Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality. Science Advances 6(15) eaaz6980. [article]

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