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dc.contributor.authorBlondeel, Eric J. M.
dc.contributor.authorAucoin, Marc
dc.date.accessioned2018-07-11 19:10:27 (GMT)
dc.date.available2018-07-11 19:10:27 (GMT)
dc.date.issued2018-09-01
dc.identifier.urihttps://dx.doi.org/10.1016/j.biotechadv.2018.06.008
dc.identifier.urihttp://hdl.handle.net/10012/13473
dc.descriptionThe final publication is available at Elsevier via https://dx.doi.org/10.1016/j.biotechadv.2018.06.008 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.description.abstractGlycosylation is a critical quality attribute (CQA) of many therapeutic proteins, particularly monoclonal antibodies (mAbs), and is a major consideration in the approval of biosimilar biologics due to its effects to therapeutic efficacy. Glycosylation generates a distribution of glycoforms, resulting in glycoproteins with inherent molecule-to-molecule heterogeneity, capable of activating (or failing to activate) different effector functions of the immune system. Glycoforms can be affected by the supplementation of nucleotide-sugar precursors, and related components, to culture growth medium, affecting the metabolism of glycosylation. These supplementations has been demonstrated to increase nucleotide-sugar intracellular pools, and impact glycoform distributions, but with varied results. These variations can be attributed to five key factors: Differences between cell platforms (enzyme/transporter expression levels); differences between recombinant proteins produced (glycan-site accessibility); the fermentation and sampling timeline (glucose availability and exoglycosidase accumulation); glutamine levels (affecting ammonia levels, which impact Golgi pH, as well as UDP-GlcNAc pools); and finally, a lack of standardized metrics for observing shifts in glycoform distributions (glycosylation indices) across different experiments. The purpose of this review is to provide detail and clarity on the state of the art of supplementation strategies for nucleotide-sugar precursors for affecting glycosylation in cell culture processes, and to apply glycosylation indices for standardized comparisons across the field.en
dc.description.sponsorshipNSERC Strategic Network Grant [MabNet-NETGP 380070-08]en
dc.language.isoenen
dc.publisherElsevieren
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAmmoniaen
dc.subjectAnimal cell cultureen
dc.subjectBiosimilaren
dc.subjectGlutamineen
dc.subjectGlycoformen
dc.subjectGlycosylationen
dc.subjectImmune effector functionsen
dc.subjectmAbsen
dc.subjectNucleotide sugarsen
dc.subjectTherapeutic proteinen
dc.titleSupplementing glycosylation: A review of applying nucleotide-sugar precursors to growth medium to affect therapeutic recombinant protein glycoform distributionsen
dc.typeArticleen
dcterms.bibliographicCitationBlondeel, E. J. M., & Aucoin, M. G. (2018). Supplementing glycosylation: A review of applying nucleotide-sugar precursors to growth medium to affect therapeutic recombinant protein glycoform distributions. Biotechnology Advances, 36(5), 1505–1523. doi:10.1016/j.biotechadv.2018.06.008en
uws.contributor.affiliation1Faculty of Engineeringen
uws.contributor.affiliation2Chemical Engineeringen
uws.typeOfResourceTexten
uws.typeOfResourceTexten
uws.peerReviewStatusRevieweden
uws.scholarLevelFacultyen


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