earticle

영어

Gaucher’s disease is a lysosomal storage disorder by mutations in the gene encoding glucocerebrosidase (GC). Gaucher’s disease is currently treated by enzyme replacement therapy using recombinant GC (CerezymeⓇ) expressed in Chinese hamster ovary (CHO) cells. As complex glycans in mammalian cells have not terminate in mannose residues, which are essential for the biological absorption of GC via macrophage mannose receptors in human patient with Gaucher’s disease, glycan modification in vitro is required in order to expose the mannose residues on the glycans of CerezymeⓇ. Notably, the recombinant human GC (rhGC) expressed in the plant cells unaffectedly contains terminal mannose residues on its complex glycan. Hence, the plant-produced rhGC does not require exposure of mannose residues in vitro, which is a requirement for the production of CerezymeⓇ. However, The presence of β1,2-xylose and core α1,3-fucose residues on plant type complex N-glycans are potentially allergic in mammals. In this study, to remove the plant specific sugar residues and customize the N-glycan structure in plant, we isolated mutants of the corresponding plant specific glycosyltransferase genes and used for multiple-mutants construction. The resulting mutants was transformed by a human α 1,6-fucosyltransferase gene to accomplish customized N-glycosylation in plant. In consequence, the production of a rhGC in a humanized N-glycosylation plant is described.