Glycoengineering of Mammalian Expression Systems on a Cellular Level
| Autor: | Qiong Wang, Michael J. Betenbaugh, Kelley M. Heffner, Deniz Baycin Hizal, Özge Can |
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| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
0301 basic medicine chemistry.chemical_classification Glycosylation Chinese hamster ovary cell HEK 293 cells Biology 01 natural sciences Cell biology carbohydrates (lipids) Glycomics 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology N-linked glycosylation chemistry 010608 biotechnology O-linked glycosylation Glycoprotein Fucosylation |
| Zdroj: | Advances in Glycobiotechnology ISBN: 9783030695897 |
| Popis: | Mammalian expression systems such as Chinese hamster ovary (CHO), mouse myeloma (NS0), and human embryonic kidney (HEK) cells serve a critical role in the biotechnology industry as the production host of choice for recombinant protein therapeutics. Most of the recombinant biologics are glycoproteins that contain complex oligosaccharide or glycan attachments representing a principal component of product quality. Both N-glycans and O-glycans are present in these mammalian cells, but the engineering of N-linked glycosylation is of critical interest in industry and many efforts have been directed to improve this pathway. This is because altering the N-glycan composition can change the product quality of recombinant biotherapeutics in mammalian hosts. In addition, sialylation and fucosylation represent components of the glycosylation pathway that affect circulatory half-life and antibody-dependent cellular cytotoxicity, respectively. In this chapter, we first offer an overview of the glycosylation, sialylation, and fucosylation networks in mammalian cells, specifically CHO cells, which are extensively used in antibody production. Next, genetic engineering technologies used in CHO cells to modulate glycosylation pathways are described. We provide examples of their use in CHO cell engineering approaches to highlight these technologies further. Specifically, we describe efforts to overexpress glycosyltransferases and sialyltransfereases, and efforts to decrease sialidase cleavage and fucosylation. Finally, this chapter covers new strategies and future directions of CHO cell glycoengineering, such as the application of glycoproteomics, glycomics, and the integration of ‘omics’ approaches to identify, quantify, and characterize the glycosylated proteins in CHO cells. |
| Databáze: | OpenAIRE |
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