Glycoengineering for the Production of Lysosomal Enzymes

Lysosomes are cellular organelles that decompose biomacromolecules, such as nucleic acids, proteins, lipids, and sugars, generated inside and outside of cells. The inside of lysosomes is maintained acidic and lysosomes contain approximately 60 types of acid hydrolases. When a defect in the genes encoding lysosomal enzymes, or in the genes encoding proteins involved in the intracellular transport of these enzymes, occurs, substrates accumulate in the cells, resulting in lysosomal storage diseases. Currently, enzyme replacement therapy is the most common treatment for lysosomal storage diseases. Enzyme replacement therapy is performed by intravenous administration of recombinant lysosomal enzymes produced in vitro. Mannose-6-phosphate receptors and mannose receptors are involved in the intracellular uptake of these recombinant lysosomal enzymes, and N-linked glycan structures on the recombinant lysosomal enzymes contribute to the uptake efficiency. This review outlines enzyme replacement therapies and discusses the current state of the glycan engineering of recombinant lysosomal enzymes.