ArticleScientific reports2018
Lysosomal Targeting Enhancement by Conjugation of Glycopeptides Containing Mannose-6-phosphate Glycans Derived from Glyco-engineered Yeast.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Sex-Specific Differences in Quality and Flavor Traits of Gonads from the Sea Urchin (Foods (Basel, Switzerland) · 2026Article
- RNA-associated glycoconjugates highlight potential ambiguities in glycoRNA analysis.Experimental & molecular medicine · 2025Article
- Effect of different cell culture media on the production and glycosylation of a monoclonal antibody from a CHO cell line.Cytotechnology · 2025Article
- Article
- Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies.Biotechnology advances · 2023Review
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Optimizing human α-galactosidase for treatment of Fabry disease.Scientific reports · 2023Article
- Glycoconjugates: Synthesis, Functional Studies, and Therapeutic Developments.Chemical reviews · 2022Review
- Mannose-6-phosphate glycan for lysosomal targeting: various applications from enzyme replacement therapy to lysosome-targeting chimeras.Animal cells and systems · 2022Article
- Chemoenzymatic glycan-selective remodeling of a therapeutic lysosomal enzyme with high-affinity M6P-glycan ligands. Enzyme substrate specificity is the name of the game.Chemical science · 2021Article
- In VitroJournal of microbiology and biotechnology · 2021Article
- Exploiting the diphtheria toxin internalization receptor enhances delivery of proteins to lysosomes for enzyme replacement therapy.Science advances · 2020Article
- Progress and challenges of gene therapy for Pompe disease.Annals of translational medicine · 2019Review
- The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells.Nature communications · 2019Article
- Pompe Disease: From Basic Science to Therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many therapeutic enzymes for lysosomal storage diseases require a high content of mannose-6-phosphate (M6P) glycan, which is important for cellular uptake and lysosomal targeting. We constructed glyco-engineered yeast harboring a high content of mannosylphosphorylated glycans, which can be converted to M6P glycans by uncapping of the outer mannose residue. In this study, the cell wall of this yeast was employed as a natural M6P glycan source for conjugation to therapeutic enzymes. The extracted cell wall mannoproteins were digested by pronase to generate short glycopeptides, which were further elaborated by uncapping and α(1,2)-mannosidase digestion steps. The resulting glycopeptides containing M6P glycans (M6PgPs) showed proper cellular uptake and lysosome targeting. The purified M6PgPs were successfully conjugated to a recombinant acid α-glucosidase (rGAA), used for the treatment of Pompe disease, by two-step reactions using two hetero-bifunctional crosslinkers. First, rGAA and M6PgPs were modified with crosslinkers containing azide and dibenzocyclooctyne, respectively. In the second reaction using copper-free click chemistry, the azide-functionalized rGAA was conjugated with dibenzocyclooctyne-functionalized M6PgPs without the loss of enzyme activity. The M6PgP-conjugated rGAA had a 16-fold higher content of M6P glycan than rGAA, which resulted in greatly increased cellular uptake and efficient digestion of glycogen accumulated in Pompe disease patient fibroblasts.
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