Mammalian cell-based production of glycans, glycopeptides and glycomodules.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Glycopeptides*/metabolism ; Glycopeptides*/chemistry ; Polysaccharides*/metabolism ; Polysaccharides*/chemistry; Humans ; Glycosylation ; Animals ; Glycoconjugates/metabolism ; Glycoconjugates/chemistry ; HEK293 Cells ; CHO Cells ; Cricetulus ; Gene Editing/methods
    • Abstract:
      Access to defined glycans and glycoconjugates is pivotal for discovery, dissection, and harnessing of a range of biological functions orchestrated by cellular glycosylation processes and the glycome. We previously employed genetic glycoengineering by nuclease-based gene editing to develop sustainable production of designer glycoprotein therapeutics and cell-based glycan arrays that display glycans in their natural context at the cell surface. However, access to human glycans in formats and quantities that allow structural studies of molecular interactions and use of glycans in biomedical applications currently rely on chemical and chemoenzymatic syntheses associated with considerable labor, waste, and costs. Here, we develop a sustainable and scalable method for production of glycans in glycoengineered mammalian cells by employing secreted Glycocarriers with repeat glycosylation acceptor sequence motifs for different glycans. The Glycocarrier technology provides a flexible production platform for glycans in different formats, including oligosaccharides, glycopeptides, and multimeric glycomodules, and offers wide opportunities for use in bioassays and biomedical applications.
      (© 2024. The Author(s).)
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    • Grant Information:
      NNF24OC0088218 Novo Nordisk Fonden (Novo Nordisk Foundation); R223-2016-563 Lundbeckfonden (Lundbeck Foundation)
    • Accession Number:
      0 (Glycopeptides)
      0 (Polysaccharides)
      0 (Glycoconjugates)
    • Publication Date:
      Date Created: 20241108 Date Completed: 20241108 Latest Revision: 20241116
    • Publication Date:
      20241116
    • Accession Number:
      PMC11549445
    • Accession Number:
      10.1038/s41467-024-53738-9
    • Accession Number:
      39516489