Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal
hydrolase. Currently,
enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic
enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic
enzymes for
Gaucher disease have N-
glycans with terminal
mannose residues for targeting to macrophages, the others require N-
glycans containing mannose-6-phosphates that are recognized by
mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic
enzymes is essential for the clearance of accumulated compounds, the suitable
glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore,
glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the
glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic
enzymes with improved efficacy.