Control of the N-Glycosylation of Therapeutic Glycoproteins Produced in Transgenic Plants: A New Challenge for Glycobiologists

The protein synthesis and folding machinery in plant and animal cells are so similar that many therapeutic proteins have already been successfully produced in transgenic plants. Most of these recombinant proteins are indistinguishable from their mammalian counterpart, as far as amino acid sequence, conformation and eventually biological activity are concerned. With regards to post-translational modifications such as glycosylation, mammalian glycoproteins are found to be glycosylated when they are produced in transgenic plants. However, plants, as other eukaryotic expression systems, are not ideal for production of pharmaceutical proteins because they produce molecules with N-glycans that differ from those on animal glycoproteins. This could represent a limitation to the use of plant-derived recombinant glycoproteins devoted to therapeutic applications since the presence of plant-specific glyco-epitopes on these molecules may elicit immune responses in humans. This has highlighted that controlling the N-glycosylation of glycoproteins is therefore a major scientific challenge on the way to obtain plant-derived recombinant glycoproteins compatible with therapeutic uses. Therefore, it seems timely to provide an update on current aspects on N-glycan processing in plants and on emerging glycobiology research on therapeutic proteins produced in transgenic plants. In this review, the first part will draw a broad overview on many aspects of the structure and the biosynthesis of plant N-glycans, as well as of the analytical tools that have been developed for the identification of these oligosaccharides. The second part will be focused on the N-glycosylation of therapeutic glycoproteins produced in transgenic plants and on the strategies that are currently developed to engineer the glycosylation in plants to obtain recombinant glycoproteins with human-like N-glycans.