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.
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