Customized protein glycosylation to improve biopharmaceutical function and targeting

• Published in: Current opinion in biotechnology Vol. 60; pp. 17 - 28
• Main Authors: Van Landuyt, Linde, Lonigro, Chiara, Meuris, Leander, Callewaert, Nico
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2019
• Subjects: Antibodies; Biological Products; Glycoproteins - metabolism; Glycosylation; Polysaccharides
• ISSN: 0958-1669; 1879-0429
• DOI: 10.1016/j.copbio.2018.11.017

[Display omitted] •Glycan customization of biopharmaceuticals allows for improved functionality and targeting.•Polysialylation results in lower clearance and improved pharmacokinetics.•Glycan minimization results in highly homogeneous biopharmaceuticals with advantages in downstream processing.•Glycoengineering and enzymatic remodelling enable to produce afucosylated antibodies with improved effector functions.•Glycoengineering of mannose or mannose-6-phosphate glycans for improved cellular and subcellular targeting. For a long time, glycoprotein production has been limited by the inherent properties of production hosts. Glycosylation of biopharmaceuticals has been regarded as a necessary evil, often needed for protein folding or function, but also a source of heterogeneity, complicating downstream processing and product characterization. This has strongly determined the choice of production hosts. Over the last few decades, numerous glycoengineering efforts have helped solving this problem. Moreover, insights from fundamental studies have made it possible to improve therapeutic protein functionality through careful glycoengineering. Here, we will focus on how production host and in vitro glycoengineering approaches allow to design biopharmaceuticals with glycans that impart improved functionality. An important branch of research explores how glycosylation can be tuned to improve pharmacokinetics and reduce glycan heterogeneity of therapeutics. Furthermore, antibody glycoengineering to obtain homogeneous, defined glycan structures has been a major focus. An example of this is the production of Fc glycans without core fucose, exhibiting tremendously improved Antibody-Dependent Cell Cytotoxicity (ADCC). In the last part, glycoforms that allow for improved (subcellular) targeting and cellular uptake, a field that opens possibilities for enzyme replacement therapies and vaccine development, will be highlighted.