Novel Approach Simplifies Complex Sugars on Protein-Based Biotech Medicines

This heterogeneity arises from the multistep process of mammalian complex-type N-glycan synthesis.

Investigators at, Ghent University (Belgium) recently described a novel glycoengineering strategy that they called GlycoDelete, which used a fungal enzyme to shorten the Golgi N-glycosylation pathway in mammalian cells.

They wrote in the April 20, 2014, online edition of the journal Nature Biotechnology that this shortening resulted in the expression of proteins with small, sialylated trisaccharide N-glycans and reduced complexity compared to native mammalian cell glycoproteins. GlycoDelete engineering did not interfere with the functioning of N-glycans in protein folding, and the physiology of cells modified by GlycoDelete was similar to that of wild-type cells. This strategy for reducing N-glycan heterogeneity on mammalian proteins could lead to more consistent performance of therapeutic proteins and modulation of biopharmaceutical functions.

Senior author Dr. Nico Callewaert, professor of medical biotechnology at Ghent University, said, “This technology has allowed us to solve an old biotech problem. Since the 1990s, nearly everyone has been working to make the sugar synthesis in biotech production cells as similar to human cells as possible. This is a very difficult task, because there are so many steps in this synthesis pathway. We have been able to create a detour in this synthesis pathway in a fairly simple manner, making the pathway much shorter and simpler.”

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