Galactose-extended glycans of antibodies produced by transgenic plants

H. Bakker, M. Bardor, J.W. Molthoff, V. Gomord, I. Elbers, L.H. Stevens, W. Jordi, A. Lommen, L. Faye, P. Lerouge, D. Bosch

Research output: Contribution to journalArticleAcademicpeer-review

262 Citations (Scopus)

Abstract

Plant-specific N-glycosylation can represent an important limitation for the use of recombinant glycoproteins of mammalian origin produced by transgenic plants. Comparison of plant and mammalian N-glycan biosynthesis indicates that β1,4-galactosyltransferase is the most important enzyme that is missing for conversion of typical plant N-glycans into mammalian-like N-glycans. Here, the stable expression of human β1,4-galactosyltransferase in tobacco plants is described. Proteins isolated from transgenic tobacco plants expressing the mammalian enzyme bear N-glycans, of which about 15% exhibit terminal β1,4-galactose residues in addition to the specific plant N-glycan epitopes. The results indicate that the human enzyme is fully functional and localizes correctly in the Golgi apparatus. Despite the fact that through the modified glycosylation machinery numerous proteins have acquired unusual N-glycans with terminal β1,4-galactose residues, no obvious changes in the physiology of the transgenic plants are observed, and the feature is inheritable. The crossing of a tobacco plant expressing human β1,4-galactosyltransferase with a plant expressing the heavy and light chains of a mouse antibody results in the expression of a plantibody that exhibits partially galactosylated N-glycans (30%), which is approximately as abundant as when the same antibody is produced by hybridoma cells. These results are a major step in the in planta engineering of the N-glycosylation of recombinant antibodies.
Original languageEnglish
Pages (from-to)2899-2904
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number5
DOIs
Publication statusPublished - 2001

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