Public Thesis defense - LIBST

Engineering N-glycosylation profile of pharmaceutical glycoproteins produced in Nicotiana tabacum BY-2 cells by Xavier HERMAN

Pour l’obtention du grade académique de Doctorat en sciences

Nicotiana tabacum BY-2 cells are among the most used plant cell lines for producing biopharmaceutical glycoproteins. However, N-glycosylation is poorly controlled, which is a concern because it can alter protein activity, raise safety concerns due to the presence of non-human residues and increase batch-to-batch variability.

To tackle these issues, we are developing a set of glyco-engineered BY-2 cell lines. We generated cell lines producing glycoproteins devoid of complex N-glycans or in vivo deglycosylated, through knocking out and ectopic expression of key genes involved in the N-glycosylation pathway. An immunoglobulin G and the glycoprotein B of human cytomegalovirus were produced in the glyco-engineered cell lines. Glycoproteomic mass spectrometry analysis of the secreted IgG, immunodetection and in vitro enzymatic mobility shift assay of glycoprotein B revealed that each cell type generates glycovariants with the anticipated N-glycan structures. In addition, we have shown that the N-glycosylation engineering affects the stability of both proteins.

Generation of glyco-engineered cell lines is a powerful tool to produce recombinant therapeutics with fine-tuned biological activities but also to broaden our understanding of the impact of N-glycans on their properties.

Jury members :

• Prof. François Chaumont (UCLouvain), supervisor
• Dr. Catherine Navarre (UCLouvain), supervisor
• Prof. Bernard Hallet (UCLouvain), chairperson
• Prof. Henri Batoko (UCLouvain), secretary
• Ms. Marianne Dewerchin (GlaxoSmithKline, Belgium)
• Prof. Muriel Bardor (Université de Rouen, France)
• Prof. Richard Strasser (BOKU, Austria)

Pay attention :

The public defense of Xavier Herman scheduled for Tuesday 31 January at 04:00 p.m. will also take place in the form of a video conference

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