Mammalian cell-based production of glycans, glycopeptides and glycomodules

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 s...

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Main Authors: Thapakorn Jaroentomeechai, Richard Karlsson, Felix Goerdeler, Fallen Kai Yik Teoh, Magnus Nørregaard Grønset, Dylan de Wit, Yen-Hsi Chen, Sanae Furukawa, Venetia Psomiadou, Ramon Hurtado-Guerrero, Elena Ethel Vidal-Calvo, Ali Salanti, Thomas J. Boltje, Leendert J. van den Bos, Christian Wunder, Ludger Johannes, Katrine T. Schjoldager, Hiren J. Joshi, Rebecca L. Miller, Henrik Clausen, Sergey Y. Vakhrushev, Yoshiki Narimatsu
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-53738-9
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author Thapakorn Jaroentomeechai
Richard Karlsson
Felix Goerdeler
Fallen Kai Yik Teoh
Magnus Nørregaard Grønset
Dylan de Wit
Yen-Hsi Chen
Sanae Furukawa
Venetia Psomiadou
Ramon Hurtado-Guerrero
Elena Ethel Vidal-Calvo
Ali Salanti
Thomas J. Boltje
Leendert J. van den Bos
Christian Wunder
Ludger Johannes
Katrine T. Schjoldager
Hiren J. Joshi
Rebecca L. Miller
Henrik Clausen
Sergey Y. Vakhrushev
Yoshiki Narimatsu
author_facet Thapakorn Jaroentomeechai
Richard Karlsson
Felix Goerdeler
Fallen Kai Yik Teoh
Magnus Nørregaard Grønset
Dylan de Wit
Yen-Hsi Chen
Sanae Furukawa
Venetia Psomiadou
Ramon Hurtado-Guerrero
Elena Ethel Vidal-Calvo
Ali Salanti
Thomas J. Boltje
Leendert J. van den Bos
Christian Wunder
Ludger Johannes
Katrine T. Schjoldager
Hiren J. Joshi
Rebecca L. Miller
Henrik Clausen
Sergey Y. Vakhrushev
Yoshiki Narimatsu
author_sort Thapakorn Jaroentomeechai
collection DOAJ
description 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.
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spelling doaj-art-c2a69eb2e97e4773a3813ca752d239d32025-08-20T02:13:26ZengNature PortfolioNature Communications2041-17232024-11-0115111610.1038/s41467-024-53738-9Mammalian cell-based production of glycans, glycopeptides and glycomodulesThapakorn Jaroentomeechai0Richard Karlsson1Felix Goerdeler2Fallen Kai Yik Teoh3Magnus Nørregaard Grønset4Dylan de Wit5Yen-Hsi Chen6Sanae Furukawa7Venetia Psomiadou8Ramon Hurtado-Guerrero9Elena Ethel Vidal-Calvo10Ali Salanti11Thomas J. Boltje12Leendert J. van den Bos13Christian Wunder14Ludger Johannes15Katrine T. Schjoldager16Hiren J. Joshi17Rebecca L. Miller18Henrik Clausen19Sergey Y. Vakhrushev20Yoshiki Narimatsu21Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenGlycoDisplay ApSCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenSynthetic Organic Chemistry, Institute for Molecules and Materials, Radboud University NijmegenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCentre for Translational Medicine and Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen University HospitalCentre for Translational Medicine and Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen University HospitalSynthetic Organic Chemistry, Institute for Molecules and Materials, Radboud University NijmegenEnzyTag BVInstitut Curie, Cellular and Chemical Biology Unit, PSL Research University, U1143 INSERM, UMR3666 CNRSInstitut Curie, Cellular and Chemical Biology Unit, PSL Research University, U1143 INSERM, UMR3666 CNRSCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenAbstract 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.https://doi.org/10.1038/s41467-024-53738-9
spellingShingle Thapakorn Jaroentomeechai
Richard Karlsson
Felix Goerdeler
Fallen Kai Yik Teoh
Magnus Nørregaard Grønset
Dylan de Wit
Yen-Hsi Chen
Sanae Furukawa
Venetia Psomiadou
Ramon Hurtado-Guerrero
Elena Ethel Vidal-Calvo
Ali Salanti
Thomas J. Boltje
Leendert J. van den Bos
Christian Wunder
Ludger Johannes
Katrine T. Schjoldager
Hiren J. Joshi
Rebecca L. Miller
Henrik Clausen
Sergey Y. Vakhrushev
Yoshiki Narimatsu
Mammalian cell-based production of glycans, glycopeptides and glycomodules
Nature Communications
title Mammalian cell-based production of glycans, glycopeptides and glycomodules
title_full Mammalian cell-based production of glycans, glycopeptides and glycomodules
title_fullStr Mammalian cell-based production of glycans, glycopeptides and glycomodules
title_full_unstemmed Mammalian cell-based production of glycans, glycopeptides and glycomodules
title_short Mammalian cell-based production of glycans, glycopeptides and glycomodules
title_sort mammalian cell based production of glycans glycopeptides and glycomodules
url https://doi.org/10.1038/s41467-024-53738-9
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