Academic Journal
GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins
| العنوان: | GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins |
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| المؤلفون: | Meuris, Leander, Santens, Francis, Elson, Greg, Festjens, Nele, Boone, Morgane, Dos Santos, Anaëlle, Devos, Simon, Rousseau, François, Plets, Evelyn, Houthuys, Erica, Malinge, Pauline, Magistrelli, Giovanni, Cons, Laura, Chatel, Laurence, Devreese, Bart, Callewaert, Nico |
| المصدر: | NATURE BIOTECHNOLOGY ; ISSN: 1087-0156 |
| سنة النشر: | 2014 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, Yeast, Glycosylation, COLONY-STIMULATING FACTOR, THERAPEUTIC ANTIBODY, IGG BINDING, LINE, EXPRESSION, RECEPTOR, ENZYME, CDNA, FCRN |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://biblio.ugent.be/publication/4389955; http://hdl.handle.net/1854/LU-4389955; http://dx.doi.org/10.1038/nbt.2885; https://biblio.ugent.be/publication/4389955/file/4389960 |
| DOI: | 10.1038/nbt.2885 |
| الاتاحة: | https://biblio.ugent.be/publication/4389955 http://hdl.handle.net/1854/LU-4389955 https://doi.org/10.1038/nbt.2885 https://biblio.ugent.be/publication/4389955/file/4389960 |
| Rights: | No license (in copyright) ; info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.6D093993 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/nbt.2885 |
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