Abstract

Exosome Engineering for Active Targeting and Intracellular Delivery of Therapeutic Proteins: Realization from Concept

Chulhee Choi, CEO, ILIAS Biologicals Inc.

As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosome offer great potential as a natural therapeutic drug delivery vehicle. Currently, both academia and industry try to develop exosome platform-based therapeutics for disease management, some of which are already in clinical trials. An optogenetically engineered exosome system (EXPLOR®) that we previously developed was implemented for loading therapeutic cargo into exosomes which can deliver therapeutic cargos into target cells in free form. We are studying the clinical potential of ‘Exo-target®’, therapeutic exosomes with EXPLOR technology, in multiple disease areas including inflammatory diseases. NF-kB has been well accepted as master regulator for inflammation. The introduction of IkB into target cells can inhibit inflammatory responses by restraining nuclear translocation of NF-kB. Therefore, we have developed Exo-target loaded with dominant active form of IkB (Exo-srIkB). We found that Exo-srIkB treatment attenuates both local and systemic inflammation and animal mortality associated inflammatory disease including sepsis, ischemic reperfusion induced acute kidney injury and preterm birth in our preclinical studies. Especially, maternally injected Exo-srIkB could cross-over placenta barrier to deliver therapeutic cargos to fetal side, which resulted in prolonged pregnancy by more than 24 hours and additional advantages. Altogether, these results suggest therapeutic value of Exo-target for various disease by delivering API intracellularly to the target cells.