Yang, Zhang9; Drew, Damian Paul2; Jørgensen, Bodil3; Poulsen, Christian Peter4; Levery, Steven Bruce5; Bennett, Eric Paul6; Ulvskov, Peter Bjarne7; Clausen, Henrik8; Petersen, Bent L4
1 Department of Molecular Biology and Genetics - Afgrødegenetik og Bioteknologi, Department of Molecular Biology and Genetics, Science and Technology, Aarhus University2 Institut for Plantebiologi og Bioteknologi3 Plante- og Jordvidenskab4 Planteglykobiologi5 Afdeling III6 Sektion 037 Molekylær Plantebiologi8 Institut for Cellulær og Molekylær Medicin9 Department of Molecular Biology and Genetics - Afgrødegenetik og Bioteknologi, Department of Molecular Biology and Genetics, Science and Technology, Aarhus University
Human mucins are large heavily O-glycosylated glycoproteins (>200 kDa), which account for the majority of proteins in mucus layers that e.g. hydrate, lubricate and protect cells from proteases as well as from pathogens. O-linked mucin glycans are truncated in many cancers, yielding truncated cancer specific glyco-peptide epitopes, such as the Tn epitope (GalNAc sugar attached to either Serine or Threonine), which are antigenic to the immune system. In the present study, we have identified plant cells as the only eukaryotic cells without mammalian type O-glycosylation or competing (for sites) O-mannosylation. Machinery and target proteins for mammalian mucin type O-glycosylation were introduced into plants and initiation of mucin type O-glycosylation (Tn) demonstrated thus providing a first proof-of-concept of developing plant based platforms for production authentic and cancer specific human type O-glycoproteins in plants, which may e.g. be used as cancer-specific vaccines.