ASEMV 2017—Engineered Exosomes with Super Repressor IkB, a Potent Inhibitor of NF-kB Pathway, for Treatment of Septic Shock

On Monday morning, October 9, Chulhee Choi, MD, PhD, of the Department of Bio and Bioengineering, KAIST, Korea; and CEO of Cellex Life Sciences, Inc., described the potential for a new system to treat acute inflammatory diseases, including septic shock. To emphasize the need for improvements in the treatment of septic shock, Dr. Choi noted that there are 20 million cases of this disease each year and that it is the leading cause of death in intensive care units. Previously, Dr. Choi’s group had developed an opto-generated engineered exosome system, named “exosomes for protein loading via optically reversible protein-protein interaction” (EXPLOR) that can deliver soluble proteins into the cytosol via controlled reversible protein-protein interactions (PPI). Treatment with protein-loaded EXPLORs was shown to significantly increase intracellular levels of cargo proteins and their function in recipient cells in both a time- and dose-dependent manner. In the current study, the group sought to test the feasibility of using EXPLOR technology for the delivery of super repressor IkB (SRI), a potent inhibitor of the NF-kB pathway, as a potential treatment for acute inflammatory diseases such as septic shock syndrome. The group was able to load SRI into engineered exosomes by transiently or stably expressing fusion proteins in exosome-producing cells. The scientists further demonstrated the intracellular delivery of SRI as functional proteins in the target cells in vitro and target organs in vivo.
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