Golgi on a chip
In this project we aim to develop a high-throughput platform to enable tailored glycan synthesis on therapeutic glycoproteins that leads to their full or even improved functionality.
Glycorotein therapeutics, like antibodies and protein containing vaccines, are of great importance for human and animal health. Many industrial protein production systems rely on eukaryotic cell lines as they harbor complex post-translational modifications. These cell lines are able to synthesize the complex glycan structures, but sometimes lack the ability to reliably synthesize specific glycan structures for optimal glycoprotein efficacy. In addition, around 96% of therapeutic glycoprotein development fail due to problems in protein stability, bioavailability, or toxicity issues, which are largely caused by erroneous protein glycosylation.
This project focusses on setting up an in vitro enzymatic glycosylation system that can be used to tailor glycans on glycoprotein drugs produced both in different protein expression systems. Initially, Golgi localized glyco-enzymes will be produced and tested for their activity and stability under in vitro conditions. These glyco-enzymes eventually will be immobilized on chips and used to generate an optimal and homogeneously glycosylated glycoprotein drug. In the future, this research can result in cheaper glycoprotein drugs with a higher efficiency and a higher stability.