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- Title
GlycoDelete engineering of mammalian cells simplifies N-glycosylation of recombinant proteins.
- Authors
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
- 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 proteins could lead to more consistent performance of therapeutic proteins and modulation of biopharmaceutical functions.
- Subjects
HETEROGENEITY; MAMMALIAN cell cycle; GLYCOSYLATION; RECOMBINANT proteins; GLYCOPROTEINS
- Publication
Nature Biotechnology, 2014, Vol 32, Issue 5, p485
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt.2885