Journal ArticleDOI
Engineered CHO cells for production of diverse, homogeneous glycoproteins.
Zhang Yang,Shengjun Wang,Adnan Halim,Morten Alder Schulz,Morten Frödin,Shamim Herbert Rahman,Malene Bech Vester-Christensen,Malene Bech Vester-Christensen,Carsten Behrens,Claus Kristensen,Sergey Y. Vakhrushev,Eric P. Bennett,Hans H. Wandall,Henrik Clausen +13 more
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TLDR
An engineering approach will aid the production of glycoproteins with improved properties and therapeutic potential by constructing a design matrix that facilitates the generation of desired glycosylation, such as human-like α2,6-linked sialic acid capping.Abstract:
Production of glycoprotein therapeutics in Chinese hamster ovary (CHO) cells is limited by the cells' generic capacity for N-glycosylation, and production of glycoproteins with desirable homogeneous glycoforms remains a challenge. We conducted a comprehensive knockout screen of glycosyltransferase genes controlling N-glycosylation in CHO cells and constructed a design matrix that facilitates the generation of desired glycosylation, such as human-like α2,6-linked sialic acid capping. This engineering approach will aid the production of glycoproteins with improved properties and therapeutic potential.read more
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Global view of human protein glycosylation pathways and functions
TL;DR: This work predicts that use of (single-cell) transcriptomics, genetic screens, genetic engineering of cellular glycosylation capacities and custom design of glycoprotein therapeutics are advancements that will ignite wider integration of gly cosylation in general cell biology.
Journal ArticleDOI
The art of CHO cell engineering: A comprehensive retrospect and future perspectives
TL;DR: This review provides a comprehensive summary of the most fundamental achievements in CHO cell engineering over the past three decades and discusses the potential of novel and innovative methodologies that might contribute to further enhancement of existing CHO based production platforms for biopharmaceutical manufacturing in the future.
Journal ArticleDOI
Decoding the Human Immunoglobulin G-Glycan Repertoire Reveals a Spectrum of Fc-Receptor- and Complement-Mediated-Effector Activities.
Gillian Dekkers,Louise W. Treffers,Rosina Plomp,Arthur E. H. Bentlage,Marcella de Boer,Carolien A. M. Koeleman,Suzanne N. Lissenberg-Thunnissen,Remco Visser,Mieke C. Brouwer,Juk Yee Mok,Hanke L. Matlung,Timo K. van den Berg,Wim J E van Esch,Taco W. Kuijpers,Diana Wouters,Theo Rispens,Manfred Wuhrer,Gestur Vidarsson +17 more
TL;DR: Fucosylation and galactOSylation are primary mediators of functional changes in IgG for FcγR- and complement-mediated effector functions, respectively, with galactose having an auxiliary role for F cγRIII-mediated functions.
Journal ArticleDOI
Therapeutic glycoprotein production in mammalian cells
TL;DR: The advance of "omics" technologies has recently given rise to new possibilities in improving these expression platforms and will significantly help developing new strategies, in particular for CHO (Chinese Hamster Ovary) cells.
Journal ArticleDOI
Global aspects of viral glycosylation.
Ieva Bagdonaite,Hans H. Wandall +1 more
TL;DR: It is underscored that glycans often pay important contributions to overall protein structure, function and immune recognition, and that glycANS represent a crucial determinant for vaccine design, to identify consensus glycosylation patterns for translational applications.
References
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Journal ArticleDOI
Biopharmaceutical benchmarks 2014
TL;DR: Monoclonal antibodies continue their march on the markets, and optimized so-called biobetter versions of existing biologics are also gaining ground, but the rate of biosimilar approvals has seen a dramatic slowdown in recent years.
Journal ArticleDOI
The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
Xun Xu,Harish Nagarajan,Nathan E. Lewis,Shengkai Pan,Zhiming Cai,Xin Liu,Wenbin Chen,Min Xie,Wenliang Wang,Stephanie Hammond,Mikael Rørdam Andersen,Norma F. Neff,Benedetto Passarelli,Winston Koh,H. Christina Fan,Jianbin Wang,Yaoting Gui,Kelvin H. Lee,Michael J. Betenbaugh,Michael J. Betenbaugh,Stephen R. Quake,Iman Famili,Bernhard O. Palsson,Jun Wang +23 more
TL;DR: A draft genomic sequence of the CHO-K1 ancestral cell line is presented and it is discussed how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.
Journal ArticleDOI
Establishment of FUT8 knockout Chinese hamster ovary cells: an ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity.
Naoko Yamane-Ohnuki,Satoko Kinoshita,Miho Inoue-Urakubo,Machi Kusunoki,Shigeru Iida,Ryosuke Nakano,Masako Wakitani,Rinpei Niwa,Mikiko Sakurada,Kazuhisa Uchida,Kenya Shitara,Mitsuo Satoh +11 more
TL;DR: The results demonstrate that FUT8−/− cells are ideal host cell lines to stably produce completely defucosylated high‐ADCC antibodies with fixed quality and efficacy for therapeutic use.
Journal ArticleDOI
Humanization of Yeast to Produce Complex Terminally Sialylated Glycoproteins
Stephen R. Hamilton,Robert C. Davidson,Natarajan Sethuraman,Juergen Hermann Nett,Youwei Jiang,Sandra Rios,Piotr Bobrowicz,Terrance A. Stadheim,Huijuan Li,Byung-Kwon Choi,Daniel Hopkins,Harry Wischnewski,Jessica Roser,Teresa I. Mitchell,Rendall R. Strawbridge,Jack Hoopes,Stefan Wildt,Tillman U. Gerngross +17 more
TL;DR: Yeast is a widely used recombinant protein expression system expanded by engineering the yeast Pichia pastoris to secrete human glycoproteins with fully complex terminally sialylated N-glycans, allowing it to replicate the sequential steps of human glycosylation.
Journal ArticleDOI
Glycoengineering: The effect of glycosylation on the properties of therapeutic proteins
Angus M. Sinclair,Steve Elliott +1 more
TL;DR: The discovery of darbepoetin alfa (DA), a hyperglycosylated analogue of erythropoietin that contains two additional N-linked carbohydrates, a threefold increase in serum half-life and increased in vivo activity compared to recombinant human ery Anthropo-EPO, is discussed.
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The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
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