Next Article in Journal
Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression
Next Article in Special Issue
Separation Options for Phosphorylated Osteopontin from Transgenic Microalgae Chlamydomonas reinhardtii
Previous Article in Journal
Expansion of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor Function in Normal and Cancer Cells: From Membrane Restructuring to Mediation of Estrogen Signaling and Stem Cell Programming
Previous Article in Special Issue
A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial Animal Cell Culture
Open AccessArticle

Implementation of Glycan Remodeling to Plant-Made Therapeutic Antibodies

Metropolitan Nashville Police Department Crime Lab, 400 Myatt Drive, Madison, TN 37115, USA
Department of Chemistry and Biochemistry, University of Maryland, 8051 Regents Drive, College Park, MD 20742, USA
iBio CDMO, 8800 Health Science Center Parkway, Bryan, TX 77807, USA
Lonza Houston, Inc., 8066 El Rio St., Houston, TX 77054, USA
MDx BioAnalytical Laboratory, Inc., 5890 Imperial loop, Suite 12, College Station, TX 77845, USA
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 421;
Received: 2 December 2017 / Revised: 9 January 2018 / Accepted: 27 January 2018 / Published: 31 January 2018
(This article belongs to the Special Issue Recombinant Proteins)
N-glycosylation profoundly affects the biological stability and function of therapeutic proteins, which explains the recent interest in glycoengineering technologies as methods to develop biobetter therapeutics. In current manufacturing processes, N-glycosylation is host-specific and remains difficult to control in a production environment that changes with scale and production batches leading to glycosylation heterogeneity and inconsistency. On the other hand, in vitro chemoenzymatic glycan remodeling has been successful in producing homogeneous pre-defined protein glycoforms, but needs to be combined with a cost-effective and scalable production method. An efficient chemoenzymatic glycan remodeling technology using a plant expression system that combines in vivo deglycosylation with an in vitro chemoenzymatic glycosylation is described. Using the monoclonal antibody rituximab as a model therapeutic protein, a uniform Gal2GlcNAc2Man3GlcNAc2 (A2G2) glycoform without α-1,6-fucose, plant-specific α-1,3-fucose or β-1,2-xylose residues was produced. When compared with the innovator product Rituxan®, the plant-made remodeled afucosylated antibody showed similar binding affinity to the CD20 antigen but significantly enhanced cell cytotoxicity in vitro. Using a scalable plant expression system and reducing the in vitro deglycosylation burden creates the potential to eliminate glycan heterogeneity and provide affordable customization of therapeutics’ glycosylation for maximal and targeted biological activity. This feature can reduce cost and provide an affordable platform to manufacture biobetter antibodies. View Full-Text
Keywords: glycan remodeling; therapeutic proteins; recombinant glycoproteins; Nicotiana benthamiana; N-glycosylation glycan remodeling; therapeutic proteins; recombinant glycoproteins; Nicotiana benthamiana; N-glycosylation
Show Figures

Graphical abstract

MDPI and ACS Style

Bennett, L.D.; Yang, Q.; Berquist, B.R.; Giddens, J.P.; Ren, Z.; Kommineni, V.; Murray, R.P.; White, E.L.; Holtz, B.R.; Wang, L.-X.; Marcel, S. Implementation of Glycan Remodeling to Plant-Made Therapeutic Antibodies. Int. J. Mol. Sci. 2018, 19, 421.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop