Targeted delivery of lysosomal enzymes to the endocytic compartment in human cells using engineered extracellular vesicles.

ABSTRACT: Targeted delivery of lysosomal enzymes to the endocytic compartment of human cells represents a transformative technology for treating a large family of lysosomal storage diseases (LSDs). Gaucher disease is one of the most common types of LSDs caused by mutations to the lysosomal β-glucocerebrosidase (GBA). Here, we describe a genetic strategy to produce engineered exosomes loaded with GBA in two different spatial configurations for targeted delivery to the endocytic compartment of recipient cells. By fusing human GBA to an exosome-anchoring protein: vesicular stomatitis virus glycoprotein (VSVG), we demonstrate that the chimeric proteins were successfully integrated into exosomes which were secreted as extracellular vesicles (EVs) by producer cells. Isolation and molecular characterizatio

SUBMITTER: Do MA 

PROVIDER: S-EPMC6872767 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature