Exosome- and extracellular vesicle-based approaches for the treatment of lysosomal storage disorders

Abstract

Cell-generated extracellular vesicles (EVs) are being engineered as biologically-inspired vehicles for targeted delivery of therapeutic agents to treat difficult-to-manage human diseases, including lysosomal storage disorders (LSDs). Engineered EVs offer distinct advantages for targeted delivery of therapeutics compared to existing synthetic and semi-synthetic nanoscale systems, for example with regard to their biocompatibility, circulation lifetime, efficiencies in delivery of drugs and biologics to target cells, and clearance from the body. Here, we review literature related to the design and preparation of EVs as therapeutic carriers for targeted delivery and therapy of drugs and biologics with a focus on LSDs. First, we introduce the basic pathophysiology of LDSs and summarize current approaches to diagnose and treat LSDs. Second, we provide specific details about EVs, including subtypes, biogenesis, biological properties and their potential to treat LSDs. Third, we review state-of-the-art approaches to engineer EVs for treatments of LSDs. Finally, we summarize explorative basic research and applied applications of engineered EVs for LSDs, and highlight current challenges, and identify new directions in developing EV-based therapies and their potential impact on clinical medicine.

Keywords: Drug delivery; Enzyme replacement therapy (ERT); Exosome; Extracellular vesicles (EVs); Gene therapy; Lysosomal storage disorders (LSDs); Microvesicles; Nanomedicine; Precision medicine; Surface display technology.