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GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins
Open accessAbstract
Heterogeneity in the N-glycans on therapeutic proteins causes difficulties for protein purification and process reproducibility and can lead to variable therapeutic efficacy. This heterogeneity arises from the multistep process of mammalian complex-type N-glycan synthesis. Here we report a glycoengineering strategy--which we call GlycoDelete--that shortens the Golgi N-glycosylation pathway in mammalian cells. This shortening results in the expression of proteins with small, sialylated trisaccharide N-glycans and reduced complexity compared to native mammalian cell glycoproteins. GlycoDelete engineering does not interfere with the functioning of N-glycans in protein folding, and the physiology of cells modified by GlycoDelete is similar to that of wild-type cells. A therapeutic human IgG expressed in GlycoDelete cells had properties, such as reduced initial clearance, that might be beneficial when the therapeutic goal is antigen neutralization. This strategy for reducing N-glycan heterogeneity on mammalian proteins could lead to more consistent performance of therapeutic proteins and modulation of biopharmaceutical functions.
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“Using this expression system for transient anti-CD-20 production, recombinant proteins had very short sialylated N-glycans with high homogeneity on the Fc domain and reduced affinity to FcγRs compared to proteins expressed in wild-type 293S.”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Meuris et al., 2014
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“GlycoDelete is an elegant glycoengineering strategy worth mentioning, which reduces glycan heterogeneity by expressing a Golgi-targeted endo-β-N-acetylglucosaminidase in HEK 293SGnTI(−) cells to produce GlcNAc N-glycan ‘stumps’ modified by galactosyltransferases and sialyltransferases to yield small sialylated trisaccharides [108].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [108]
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“Furthermore, to improve N-glycan homogeneity on therapeutic proteins, a technique called “GlycoDelete” engineering was also recently developed in HEK293S cells (Meuris et al., 2014).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Meuris et al., 2014
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1 retracted
RETRACTED: Dominant suppression of inflammation by glycan-hydrolyzed IgG
Nandakumar, K. S., Collin, M., Happonen, K. E., Croxford, A. M., Lundström, S. L., Zubarev, R. A., Rowley, M. J., Blom, A. M., & Holmdahl, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301480110 · Cited by 20
RetractedSkyline: an open source document editor for creating and analyzing targeted proteomics experiments
MacLean, B., Tomazela, D. M., Shulman, N., Chambers, M., Finney, G. L., Frewen, B., Kern, R., Tabb, D. L., Liebler, D. C., & MacCoss, M. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq054 · Cited by 4,697
FcRn: the neonatal Fc receptor comes of age
Roopenian, D. C., & Akilesh, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2155 · Cited by 2,346
Mössner, E., Brünker, P., Moser, S., Püntener, U., Schmidt, C., Herter, S., Grau, R., Gerdes, C. A., Nopora, A., van Puijenbroek, E., et al. (2010) · Blood · doi:10.1182/blood-2009-06-225979 · Cited by 983
An improved colorimetric assay for interleukin 2
Tada, H., Shiho, O., Kuroshima, K.-I., Koyama, M., & Tsukamoto, K. (1986) · Journal of Immunological Methods · doi:10.1016/0022-1759(86)90183-3 · Cited by 871
Thermofluor-based high-throughput stability optimization of proteins for structural studies
Ericsson, U. B., Hällberg, B. M., DeTitta, G. T., Dekker, N., & Nordlund, P. (2006) · Analytical Biochemistry · doi:10.1016/j.ab.2006.07.027 · Cited by 840
Glycosylation as a strategy to improve antibody-based therapeutics
Jefferis, R. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2804 · Cited by 829
Kitamura, T., Tange, T., Terasawa, T., Chiba, S., Kuwaki, T., Miyagawa, K., Piao, Y., Miyazono, K., Urabe, A., & Takaku, F. (1989) · Journal of Cellular Physiology · doi:10.1002/jcp.1041400219 · Cited by 784
Reeves, P. J., Callewaert, N., Contreras, R., & Khorana, H. G. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212519299 · Cited by 641
Self-citationIntracellular Signaling by the Unfolded Protein Response
Bernales, S., Papa, F. R., & Walter, P. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.122303.120200 · Cited by 543
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Proteomics in the genome engineering era
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Posttranslational modifications of heterologous proteins expressed in Nicotiana benthamiana
Göritzer, K., Kallolimath, S., & Strasser, R. (2025) · Plant Biotechnology Journal · doi:10.1111/pbi.70176 · Cited by 9
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Chatterjee, J., Walensky, J. R., Kundu, S., Biswas, G., Maji, K., & Sarkar, R. (2025) · Organic & Biomolecular Chemistry · doi:10.1039/d5ob01076d · Cited by 9
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Holgado, A., Braun, H., Verstraete, K., Vanneste, D., Callewaert, N., Savvides, S. N., Afonina, I. S., & Beyaert, R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01422 · Cited by 9
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Guan, Y., Zhang, M., Gaikwad, M., Voß, H., Fazel, R., Ansari, S., Shen, H., Wang, J., & Schlüter, H. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00221 · Cited by 7
Ivanova, A., & Falcioni, F. (2022) · Frontiers in Catalysis · doi:10.3389/fctls.2021.810779 · Cited by 5
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Thooft, K., Breedam, W. V., Santens, F., Wyseure, E., Vanmarcke, S., Devos, S., Callewaert, N., & Madder, A. (2021) · Organic & Biomolecular Chemistry · doi:10.1039/d1ob02299g · Cited by 6
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DeWinter, M. A., Wong, D. A., Fernandez, R., Kightlinger, W., Thames, A. H., DeLisa, M. P., & Jewett, M. C. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.4c00228 · Cited by 5
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Gupta, M. D. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.739559298.793586334
Spearman, M. A., Lattová, E., Perreault, H., & Butler, M. (2018) · Wiley eBooks · doi:10.1002/9781119378341.ch3
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Herwig, C. (2018) · MDPI eBooks · doi:10.3390/books978-3-03842-746-9
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Metadata
- Authors
- Meuris, L., Santens, F., Elson, G., Festjens, N., Boone, M., Dos Santos, A., Devos, S., Rousseau, F., Plets, E., Houthuys, E., Malinge, P., Magistrelli, G., Cons, L., Chatel, L., Devreese, B., & Callewaert, N.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- Light Chain Bioscience (Switzerland) (CH)
- Ghent University (BE)
- Corresponding author
- Callewaert, Nico
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2014-04-20
- Volume
- 32
- Issue
- 5
- Pages
- 485-489
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC7039703
- OpenAlex
- W1965443132
- Cited by
- 141
- References
- 31
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 8 · 2021: 12 · 2020: 16 · 2019: 7 · 2018: 22 · 2017: 16 · 2016: 15 · 2015: 16 · 2014: 6
- FWCI
- 7.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek (G.0.541.08.N.10)
- Universiteit Gent
- Vlaamse regering
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Transgenic Plants and Applications
- Keywords
- N-glycosylation, glycoengineering, recombinant protein expression, protein clearance, glycoprotein folding, biopharmaceuticals
- MeSH terms
- Animals, Glycosylation, Humans, Polysaccharides, Recombinant Proteins, Protein Engineering, Mice
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