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Production of plant made pharmaceuticals: from plant host to functional protein

Bieke Nagels (UGent) , K Weterings, Nico Callewaert (UGent) and Els Van Damme (UGent)
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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
expression, glycosylation, biological function, molecular farming, plant, therapeutic protein, N-GLYCOSYLATION PATHWAY, DEPENDENT CELLULAR CYTOTOXICITY, CMP-SIALIC ACID, GLYCAN PROCESSING ENZYMES, LEPIDOPTERAN INSECT CELLS, ZINC-FINGER NUCLEASES, RECOMBINANT HUMAN LACTOFERRIN, CORE ALPHA-1, 3-LINKED FUCOSE, ARABIDOPSIS-THALIANA PLANTS, HUMAN MONOCLONAL-ANTIBODY

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Chicago
Nagels, Bieke, K Weterings, Nico Callewaert, and Els Van Damme. 2012. “Production of Plant Made Pharmaceuticals: From Plant Host to Functional Protein.” Critical Reviews in Plant Sciences 31 (2): 148–180.
APA
Nagels, B., Weterings, K., Callewaert, N., & Van Damme, E. (2012). Production of plant made pharmaceuticals: from plant host to functional protein. CRITICAL REVIEWS IN PLANT SCIENCES, 31(2), 148–180.
Vancouver
1.
Nagels B, Weterings K, Callewaert N, Van Damme E. Production of plant made pharmaceuticals: from plant host to functional protein. CRITICAL REVIEWS IN PLANT SCIENCES. 2012;31(2):148–80.
MLA
Nagels, Bieke, K Weterings, Nico Callewaert, et al. “Production of Plant Made Pharmaceuticals: From Plant Host to Functional Protein.” CRITICAL REVIEWS IN PLANT SCIENCES 31.2 (2012): 148–180. Print.
@article{2140386,
  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.},
  author       = {Nagels, Bieke and Weterings, K and Callewaert, Nico and Van Damme, Els},
  issn         = {0735-2689},
  journal      = {CRITICAL REVIEWS IN PLANT SCIENCES},
  keyword      = {expression,glycosylation,biological function,molecular farming,plant,therapeutic protein,N-GLYCOSYLATION PATHWAY,DEPENDENT CELLULAR CYTOTOXICITY,CMP-SIALIC ACID,GLYCAN PROCESSING ENZYMES,LEPIDOPTERAN INSECT CELLS,ZINC-FINGER NUCLEASES,RECOMBINANT HUMAN LACTOFERRIN,CORE ALPHA-1,3-LINKED FUCOSE,ARABIDOPSIS-THALIANA PLANTS,HUMAN MONOCLONAL-ANTIBODY},
  language     = {eng},
  number       = {2},
  pages        = {148--180},
  title        = {Production of plant made pharmaceuticals: from plant host to functional protein},
  url          = {http://dx.doi.org/10.1080/07352689.2011.616075},
  volume       = {31},
  year         = {2012},
}

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