Humanising and helminthising glycans in plants: new prospects for production and application of biopharmaceutical proteins

Description

Secretory glycoproteins are in the spotlight as biopharmaceuticals in therapeutic applications. An array of human glycoproteins, notably antibodies, is currently produced in heterologous hosts and many new candidates are being developed for drug applications. Recently, helminth glycoproteins showed to be promising biopharmaceuticals based on their glycan-dependent immunomodulatory properties. For the production of these glycoproteins a flexible and amenable production platform is required that allows the synthesis of defined glycans. Plants fulfill these criteria and are highly flexible regarding glyco-engineering as they tolerate adaptations of their N-glycosylation machinery. Compared to mammalian cell culture systems the glycans obtained in plants are remarkably homogeneous. Also, unintended alterations in glycan structures can be better ‘managed’ in plants. Such alterations may be a consequence of the protein environment, sometimes leading to unexpected glycans. Glyco-engineering in the plant Nicotiana benthamiana is accomplished by the controlled expression of an array of glycosyltransferases. We generated human-like glycans on interleukin-22 by co-expression of 1,6-fucosyltransferase (FUT8). Co-expression of, a fucosyl- and galactosyltransferase with the immunomodulatory Schistosoma mansoni egg derived omega-1 glycoprotein yielded Lewis X (Lex) structures, the motive that is naturally present on this protein. We showed that the immunomodulatory properties of omega-1 are glycan dependent by comparison with omega-1 possessing native plant glycans. Thus, plants show to be a promising platform for the production of glycoproteins to be used as biopharmaceuticals.

Period	22 Apr 2016
Event type	Seminar
Location	Leiden, Netherlands