| Literature DB >> 10545921 |
S Weikert1, D Papac, J Briggs, D Cowfer, S Tom, M Gawlitzek, J Lofgren, S Mehta, V Chisholm, N Modi, S Eppler, K Carroll, S Chamow, D Peers, P Berman, L Krummen.
Abstract
We have engineered two Chinese hamster ovary cell lines secreting different recombinant glycoproteins to express high levels of human beta1,4-galactosyltransferase (GT, E.C. 2.4.1.38) and/or alpha2, 3-sialyltransferase (ST, E.C. 2.4.99.6). N-linked oligosaccharide structures synthesized by cells overexpressing the glycosyltransferases showed greater homogeneity compared with control cell lines. When GT was overexpressed, oligosaccharides terminating with GlcNAc were significantly reduced compared with controls, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. As expected, GT overexpression resulted in reduction of oligosaccharides terminating with GlcNAc, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. The more highly sialylated glycoproteins had a significantly longer mean residence time in a rabbit model of pharmacokinetics. These experiments demonstrate the feasibility of genetically engineering cell lines to produce therapeutics with desired glycosylation patterns.Entities:
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Year: 1999 PMID： 10545921 DOI： 10.1038/15104
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908