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Production of Plant Made Pharmaceuticals: From Plant Host to Functional Protein
Authors:B. Nagels  K. Weterings  N. Callewaert  E. J. M. Van Damme
Affiliation:1. Laboratory of Biochemistry and Glycobiology, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653 , Ghent , Belgium;2. Bayer BioScience N.V. Technologiepark 38 , Ghent , Belgium;3. Bayer CropScience Innovation Center, 3500 Paramount Parkway , Morrisville , NC , USA;4. Unit for Medical Biotechnology, Department for Molecular Biomedical Research, VIB, Technologiepark 927 , Ghent , Belgium;5. L-Probe, Department of Biochemistry and Microbiology, Faculty of Sciences, Ghent University, K. Ledeganckstraat 35 , Ghent , Belgium;6. Laboratory of Biochemistry and Glycobiology, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653 , Ghent , Belgium
Abstract:In the last two decades plants have emerged as valuable alternatives to mammalian cells for the production of pharmaceuticals and their potential as expression systems was shown by the commercial availability and acceptance of several plant made therapeuticals in clinical trials. Plants have many advantages over yeast, insect and bacterial expression systems such as the potential to properly fold the expressed proteins and the synthesis of more human-like N-glycans on the proteins. However, several constraints, such as expression yields, downstream processing and structural authenticity, currently limit the widespread use of plant expression systems. In this review, the focus is on the current limitations of plant systems for the production of pharmaceuticals and the possibilities to overcome these obstacles. A comparison is made with insect cell and yeast expression systems. Furthermore, the importance of glycosylation, in particular N-glycosylation for the biological function(s) of therapeutics in the human body will be discussed in detail and an overview of the state of art in the humanization of the N-glycosylation pathway in plants is provided.
Keywords:biological function  expression  glycosylation  molecular farming  plant  therapeutic protein
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