Treatment of Gaucher disease with exosome-based glucocerebrosidase replacement

Abstract

Many intracellular proteins with great potential as biopharmaceutical drugs have been identified

however, numerous challenges associated with intracellular protein delivery have yet to be solved. Recent studies have sought to use exosomes as a new method for the in vivo delivery of various cargos to specific target tissues by systemic injection. Soluble proteins can be loaded into the exosome via controlled, reversible, light-induced protein-protein interactions (PPI) named "exosomes for protein loading via optically reversible protein-protein interaction” (EXPLOR). I utilized opto-genetically engineered exosome system to load β-glucocerebrosidase (GBA), which is an enzyme deficient in Gaucher disease patients, into newly generated exosomes. In the present study, I demonstrated the intracellular delivery of beta-glucocerebrosidase as functional proteins from the exosomes to the target cells, indicating the potential of EXPLOR for treatment of Gaucher disease.