Glycoengineering in plants for the development of N-glycan structures compatible with biopharmaceuticals

Abstract

Plants and plant cells are emerging as promising alternatives for biopharmaceutical production with improved safety and efficiency. Plant cells are capable of performing post-translational modifications (PTMs) similar to those of mammalian cells and are safer than mammalian cells with regard to contamination by infectious pathogens, including animal viruses. However, a major obstacle to producing biopharmaceuticals in plants lies in the fact that plant-derived N-glycans include plant-specific sugar residues such as beta 1,2-xylose and alpha 1,3-fucose attached to a pentasaccharide core (Man(3)GlcNAc(2)) as well as beta 1,3-galactose and alpha 1,4-fucose involved in Lewis a (Le(a)) epitope formation that can evoke allergic responses in the human body. In addition, sugar residues such as alpha 1,6-fucose, beta 1,4-galactose and alpha 2,6-sialic acid, which are thought to play important roles in the activity, transport, delivery and half-life of biopharmaceuticals are absent among the N-glycans naturally found in plants. In order to take advantage of plant cells as a system in which to produce biopharmaceuticals development of plants producing N-glycan structures compatible with biopharmaceuticals is necessary. In this article we summarize the current state of biopharmaceutical production using plants as well as what is known about N-glycosylation processes occurring in the endoplasmic reticulum and Golgi apparatus in plants. Finally, we propose and discuss a strategy for and the associated technical barriers of producing customized N-glycans via removal of enzyme genes that add plant-specific sugar residues and introducing enzyme genes that add sugar residues absent in plants.