Engineering of Nicotiana benthamiana plants for the production of O-glycosylated recombinant proteins
Abstract
Many recombinant biopharmaceuticals that are approved for human use are glycoproteins. Glycosylation of recombinant therapeutic proteins affects their structural and functional properties. Control of glycosylation is therefore a critical step to enhance the efficacy of therapeutics and eliminate unwanted side effects resulting from non-authentic glycosylation. Current production technologies for recombinant glycoproteins are mainly based on expression in mammalian cells, which do not allow the efficient manipulation of glycosylation and thus contain heterogeneous glycans. This project aims to provide a plant-based expression platform for the production of recombinant glycoproteins with a customized glycosylation profile. Recent developments in modification of the N-glycosylation pathway have shown that green plants are a versatile expression system for the generation of therapeutic proteins with a defined human-type N-glycosylation. We have shown that engineered Nicotiana benthamiana plants can very efficiently produce recombinant biopharmaceuticals like human erythropoietin with homogenous N-glycans carrying sialic acid. In this project, we aim to achieve the generation of distinct O-glycan structures on recombinant proteins using our established plant-based production platform. To this end, we will express all proteins required for the initiation and extension of human mucin-type O-glycosylation in N. benthamiana plants together with different O-glycosylated therapeutically relevant proteins. All generated glycan structures will be validated and tested for their influence on the biological activity of the recombinant biopharmaceuticals. Moreover, we will combine our technologies for N- and O-glycan engineering to develop a production system for recombinant glycoproteins with controlled human-type N- and O-glycosylation, which should advance the development of novel protein-based therapeutics.
recombinant proteins glycoprotein molecular farming glycobiology
Publikationen
Project staff
Richard Strasser
Assoc. Prof. Dr. Richard Strasser
richard.strasser@boku.ac.at
Tel: +43 1 47654-94345
Project Leader
01.07.2012 - 31.10.2016
BOKU partners
External partners
Arizona State University
Hugh Mason
partner