ArticleMolecular therapy. Methods & clinical development2017
Engineering of GlcNAc-1-Phosphotransferase for Production of Highly Phosphorylated Lysosomal Enzymes for Enzyme Replacement Therapy.
Article in Molecular therapy. Methods & clinical development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Revisiting Enzyme Replacement Therapy for Aspartylglucosaminuria: Truncated Phosphotransferase Enhances Mannose-6-Phosphorylation and Cellular Uptake of Aspartylglucosaminidase.Journal of inherited metabolic disease · 2026Article
- Subtle cellular phenotypes inform pathological and benign genetic mutants in the Iduronate-2 sulfatase gene.Human molecular genetics · 2026Article
- GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.JCI insight · 2025Article
- Age-sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- LYSET facilitates integration of both the N- and C-terminal transmembrane helices/cytoplasmic domains of GlcNAc-1-phosphotransferase.Molecular biology of the cell · 2025Article
- Structural and Functional Insights into the Stealth Protein CpsY ofBiomolecules · 2023Article
- Article
- Targeted protein degradation using the lysosomal pathway.RSC medicinal chemistry · 2022Review
- Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep.The Journal of clinical investigation · 2022Article
- Structures of the mannose-6-phosphate pathway enzyme, GlcNAc-1-phosphotransferase.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structure of the human GlcNAc-1-phosphotransferase αβ subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation.Nature structural & molecular biology · 2022Article
- Mannose-6-phosphate glycan for lysosomal targeting: various applications from enzyme replacement therapy to lysosome-targeting chimeras.Animal cells and systems · 2022Article
- Increased phosphorylation of HexM improves lysosomal uptake and potential for managing GM2 gangliosidoses.BBA advances · 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
- Elevated mRNA expression and defective processing of cathepsin D in HeLa cells lacking the mannose 6-phosphate pathway.FEBS open bio · 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
- Article
- Cell-autonomous expression of the acid hydrolase galactocerebrosidase.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Dual-Functional Titanium(IV) Immobilized Metal Affinity Chromatography Approach for Enabling Large-Scale Profiling of Protein Mannose-6-Phosphate Glycosylation and Revealing Its Predominant Substrates.Analytical chemistry · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Several lysosomal enzymes currently used for enzyme replacement therapy in patients with lysosomal storage diseases contain very low levels of mannose 6-phosphate, limiting their uptake via mannose 6-phosphate receptors on the surface of the deficient cells. These enzymes are produced at high levels by mammalian cells and depend on endogenous GlcNAc-1-phosphotransferase α/β precursor to phosphorylate the mannose residues on their glycan chains. We show that co-expression of an engineered truncated GlcNAc-1-phosphotransferase α/β precursor and the lysosomal enzyme of interest in the producing cells resulted in markedly increased phosphorylation and cellular uptake of the secreted lysosomal enzyme. This method also results in the production of highly phosphorylated acid β-glucocerebrosidase, a lysosomal enzyme that normally has just trace amounts of this modification.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.