Increasing the sialylation of therapeutic glycoproteins: The potential of the sialic acid biosynthetic pathway

• Published in: Journal of pharmaceutical sciences Vol. 98; no. 10; pp. 3499 - 3508
• Main Authors: Bork, Kaya, Horstkorte, Rüdiger, Weidemann, Wenke
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.10.2009; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Animals; Biological and medical sciences; Biotransformation; Enzymes - biosynthesis; General pharmacology; Glycoproteins - chemical synthesis; Glycoproteins - therapeutic use; Glycosylation; Humans; Medical sciences; N-Acetylneuraminic Acid - biosynthesis; N-Acetylneuraminic Acid - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polysaccharides - biosynthesis; protein stability; recombinant glycoproteins; Recombinant Proteins - chemical synthesis; Recombinant Proteins - therapeutic use; sialic acid; Sialic Acids - chemistry; Sialic Acids - immunology; therapeutic proteins; recombinant glycoproteins; sialic acid; protein stability; therapeutic proteins; Sialic acid; Stability; Pharmaceutical technology; Treatment; Glycoprotein; Physicochemical properties; Protein
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.21684

The number of therapeutic proteins has increased dramatically over the past years and most of the therapeutic proteins in the market today are glycoproteins. Usually, recombinant glycoproteins are produced in mammalian cell lines, such as Chinese-hamster-ovary-cells to obtain mammalian-type of glycosylation. The terminal monosaccharide of N-linked complex glycans is typically occupied by sialic acid. Presence of this sialic acid affects absorption, serum half-life, and clearance from the serum, as well as the physical, chemical and immunogenic properties of the respective glycoprotein. From a manufacturing perspective, the degree of sialylation is crucial since sialylation varies the function of the product. In addition, insufficient or inconsistent sialylation is also a major problem for the process consistency. Sialylation of over-expressed glycoproteins in all mammalian cell lines commonly used in biotechnology for the production of therapeutic glycoproteins is incomplete and there is a need for strategies leading to homogenous, naturally sialylated glycoproteins. This review will shortly summarize the biosynthesis of sialic acids and describe some recent strategies to increase or modify sialylation of specific therapeutic glycoproteins. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3499–3508, 2009