Mannose-6-phosphate glycan for lysosomal targeting: various applications from enzyme replacement therapy to lysosome-targeting chimeras

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Title
Mannose-6-phosphate glycan for lysosomal targeting: various applications from enzyme replacement therapy to lysosome-targeting chimeras
Author(s)
Jinho SeoDoo-Byoung Oh
Bibliographic Citation
Animal Cells and Systems, vol. 26, no. 3, pp. 84-91
Publication Year
2022
Abstract
A lysosome, an acidic membrane-bound organelle, contains hydrolytic enzymes to digest macromolecules for recycling. Many lysosomal enzymes (LEs) traffic to the lysosome through the mannose-6-phosphate (M6P)-dependent pathway. Some mannose residues of high-mannose type N-glycans on LEs can be phosphorylated in the Golgi apparatus through two-step enzyme reactions. The consequent M6P moiety is recognized by M6P receptors (MPRs) on the trans-Golgi network membrane and delivered through the endo-lysosomal pathway. On the other hand, secreted LEs containing M6P glycans can be recaptured by MPRs on the plasma membrane and targeted to the lysosome. Enzyme replacement therapy (ERT) for lysosomal storage diseases exploits this M6P-MPR-dependent endocytosis to deliver recombinant enzymes to lysosomes. This review discusses various engineering and application technologies using M6P's lysosomal targeting. Glyco-engineering for increasing M6P contents developed 'Bio-better' ERT enzymes with enhanced therapeutic efficacy. M6P-decorated peptides, proteins, liposomes, and nanoparticles have been developed for drug delivery and subcellular imaging. A recently developed lysosome-targeting chimera uses an M6P-based bifunctional binder to degrade specific extracellular and membrane proteins. The success and efficiency of M6P-based lysosomal targeting will boost further technological developments with new applications in the biomedical field.
Keyword
Mannose-6-phosphateLysosomeGlycanEnzyme replacement theraphy and lysosome-targeting chimera
ISSN
1976-8354
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.1080/19768354.2022.2079719
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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