Developing genetic and chemical strategies for glycoprotein engineering

Glycosylation is the most diverse post-translational modification of proteins and largely contributes to the staggering diversity of proteoforms found in cells, tissues, and organisms. Human glycans are assembled by ca. 200 glycosyltransferases in the ER/Golgi system. Genetic engineering can be used to alter the expression of glycosyltransferases and thus the glycan output of a cell. Using precise genome editing tools, we stably delete and insert specific combinations of glycosyltransferases to generate cells that assemble specific glycan structures. We use these cells to recombinantly produce glycoproteins that then carry these glycans. Moreover, we introduce chemically modified sugar building blocks into cells to incorporate them into glycans. These modifications allow us to change the functionality of glycoproteins and to steer glycan interactions.