N-Glycosylation Modification of Plant-Derived Virus-Like Particles: An Application in Vaccines

Figure 2

Schematic diagram of humanization of the glycosylation pathway in plant. In ER, protein is glycosylated and three glucoses are removed from the attached glycan. The glycoproteins then are transferred to the Golgi complex where mannoses are trimmed, and the glycoresidues are sequentially attached. When the ER retention signal KDEL sequence is attached to the C-terminal of glycoproteins, glycoproteins are retained and accumulated in the ER. Plant glycans carry β1,2-xylose and α1,3-fucose residues attached to the N-acetylglucosamine whereas human glycans contain α1,6-fucose, β1,4-galactose, and α2,3,6-sialic acid. In humanization glycoengineering process the β1,2-XylT and α1,3-FucT should be knocked out to remove xylose and fucose, respectively. The β1,4-GalT should be knocked in to add β1,4-galactose. Furthermore, finally CMP-sialic acid synthetase, sialic acid synthase, and α2,3,6-sialic transferase should be knocked in to attach α2,3,6-sialic acid to the terminal galactose. KDEL: ER retention motif (Lys-Asp-Glu-Leu), β1,2-XylT: β1,2-xylose transferase, α1,3-FucT: α1,3-fucose transferase, β1,4-GalT: β1,4-galactosidase, α2,3,6-SialyT: α2,3,6-sialic transferase.