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GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins

(2014) NATURE BIOTECHNOLOGY. 32(5). p.485-489
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Abstract
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 protins could lead to more consistent performance of therapeutic proteins and modulation of biopharmaceutical functions.
Keywords
Yeast, Glycosylation, COLONY-STIMULATING FACTOR, THERAPEUTIC ANTIBODY, IGG BINDING, LINE, EXPRESSION, RECEPTOR, ENZYME, CDNA, FCRN

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Chicago
Meuris, Leander, Francis Santens, Greg Elson, Nele Festjens, Morgane Boone, Anaëlle Dos Santos, Simon Devos, et al. 2014. “GlycoDelete Engineering of Mammalian Cells Simplifies N-glycosylation of Recombinant Proteins.” Nature Biotechnology 32 (5): 485–489.
APA
Meuris, L., Santens, F., Elson, G., Festjens, N., Boone, M., Dos Santos, A., Devos, S., et al. (2014). GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins. NATURE BIOTECHNOLOGY, 32(5), 485–489.
Vancouver
1.
Meuris L, Santens F, Elson G, Festjens N, Boone M, Dos Santos A, et al. GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins. NATURE BIOTECHNOLOGY. 2014;32(5):485–9.
MLA
Meuris, Leander, Francis Santens, Greg Elson, et al. “GlycoDelete Engineering of Mammalian Cells Simplifies N-glycosylation of Recombinant Proteins.” NATURE BIOTECHNOLOGY 32.5 (2014): 485–489. Print.
@article{4389955,
  abstract     = {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 protins could lead to more consistent performance of therapeutic proteins and modulation of biopharmaceutical functions.},
  author       = {Meuris, Leander and Santens, Francis and Elson, Greg and Festjens, Nele and Boone, Morgane and Dos Santos, Ana{\"e}lle and Devos, Simon and Rousseau, Fran\c{c}ois and Plets, Evelyn and Houthuys, Erica and Malinge, Pauline and Magistrelli, Giovanni and Cons, Laura and Chatel, Laurence and Devreese, Bart and Callewaert, Nico},
  issn         = {1087-0156},
  journal      = {NATURE BIOTECHNOLOGY},
  language     = {eng},
  number       = {5},
  pages        = {485--489},
  title        = {GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins},
  url          = {http://dx.doi.org/10.1038/nbt.2885},
  volume       = {32},
  year         = {2014},
}

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