Mammalian cell-based production of glycans, glycopeptides and glycomodules
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.
Authors
- Katrine T. Schjoldager (ORCID: https://orcid.org/0000-0002-8592-6763)
- Felix Goerdeler (ORCID: https://orcid.org/0000-0002-7190-9145)
- Christian Wunder (ORCID: https://orcid.org/0000-0001-9091-0080)
- Hiren J. Joshi (ORCID: https://orcid.org/0000-0002-8192-2829)
- Thomas J. Boltje (ORCID: https://orcid.org/0000-0001-9141-8784)
- Yoshiki Narimatsu (ORCID: https://orcid.org/0000-0003-1428-5695)
- Sergey Y. Vakhrushev (ORCID: https://orcid.org/0000-0002-0418-5765)
- Thapakorn Jaroentomeechai (ORCID: https://orcid.org/0000-0003-2235-7820)
- Henrik Clausen (ORCID: https://orcid.org/0000-0002-0915-5055)
- Venetia Psomiadou
- Elena Ethel Vidal-Calvo (ORCID: https://orcid.org/0000-0001-9655-2106)
- Richard Karlsson (ORCID: https://orcid.org/0000-0003-0448-6135)
- Ramón Hurtado‐Guerrero (ORCID: https://orcid.org/0000-0002-3122-9401)
- Yen‐Hsi Chen (ORCID: https://orcid.org/0000-0001-9484-3145)
- Ludger Johannes (ORCID: https://orcid.org/0000-0002-2168-0004)
- Leendert J. van den Bos (ORCID: https://orcid.org/0000-0003-2410-5838)
- Rebecca L. Miller (ORCID: https://orcid.org/0000-0001-8574-1948)
- Ali Salanti (ORCID: https://orcid.org/0000-0003-2207-5575)
- Magnus Nørregaard Grønset (ORCID: https://orcid.org/0000-0002-2582-5063)
- Sanae Furukawa
- Dominique De Wit
- Fallen Kai Yik Teoh
Institutions
- University of Copenhagen (DK)
- Centre National de la Recherche Scientifique (FR)
- Radboud University Nijmegen (NL)
- Inserm (FR)
- Universidad de Zaragoza (ES)
- Université Paris Sciences et Lettres (FR)
- Copenhagen University Hospital (DK)
- Fundacion Agencia Aragonesa para la Investigacion y el Desarrollo (ES)
- YKK (Japan) (JP)
- Institut Curie (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-08
- DOI
- https://doi.org/10.1038/s41467-024-53738-9
- Citations
- 11
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- Innovationsfonden
- Lundbeckfonden
- Novo Nordisk
- Faculty of Health and Medical Sciences, University of Western Australia
- Novo Nordisk Fonden
- H. Lundbeck A/S
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet