Novel chemical approaches in CHO sialic acid analog glycoengineering

Cell culture;Glycoengineering;Sialic Acid;ManNAc;Glycosylation;Chemical & Biomolecular Engineering

Stuczynski, Mark C.Betenbaugh, Michael J. ;

Johns Hopkins University

关键词: Cell culture;    Glycoengineering;    Sialic Acid;    ManNAc;    Glycosylation;    Chemical & Biomolecular Engineering;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/44604/Thesis%20R1.pdf?sequence=2&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Biophamaceuticals promise a wide variety of benefits to modern medicine. The ability to produce highly effective, low-cost treatments for genetic diseases and other illnesses places a high degree of importance on biopharmaceutical techniques. Acting in concert or as an analogous replacement, biopharmaceutical proteins are a bold, promising technology poised to have major impacts on human health. Glycoproteins are a particularly well-researched biotherapeutics class that display high specificity and efficacy in treating numerous diseases.Bulk production of protein therapeutics requires careful monitoring of many factors. Cell type, media quantification, and glycosylation patterning are all relevant points of analysis. Glycosylation in particular, how sugar structures are assembled on amino acid residues, is an extremely important regulatory mechanism. Chinese hamster ovary cells are often used in order to provide a viable production platform with human-similar glycosylation. Within glycosylation, it has been found that terminal sialic acid (N-acetylneuraminic acid, NeuAc, NeuGc) content on the glycan correlates with many positive in vivo effects, including increased half-life, reduced clearance, and more direct site recognition. Because of the importance of terminal sialic acid, many techniques exploit differing aspects of cell biology in order to increase the volume of terminal sialic acid. We study the effects of chemical biology and the utilization of analogs of ManNAc, a sialic acid precursor commonly used to increase available cellular sialic acid as a biochemical approach to promote sialic acid availability.