Advancing Bioconjugation: GlyPROCLICK's Journey in Glycoprotein Innovation

The GlyPROCLICK project (GLYcan remodeling for PROtein bioconjugation by CLICK reactions), a Walloon initiative focused on establishing an advanced bioconjugation service and developing self-reliant intellectual property in site-selective modifications, has concluded its path.

This article explores the project's key outcomes, hurdles overcome, and potential impact on the biotech industry. As a project insider, I, Riccardo Marega, will provide unique insights into this innovative venture that's set to reshape glycoprotein-based biologics.

Transforming Protein Modification

GlyPROCLICK, backed by the Walloon Region through the Win4Collective fund scheme and guided by a consortium of SMEs (Unisensor, Coris Bioconcept, Lacard/Zentech, D-Tek, Alphadia, Immunochem), UNamur and a large enterprise (EurogenTech), has successfully developed new technologies for glycoprotein modification. Our team's work spans from glycan modification and bioconjugation optimization to enzyme production and structural characterization of bioconjugates.

A major achievement is our patent-pending technology for site-selective modification of glycoproteins (WO2023232782A1), including antibodies. This innovation's significance was independently validated by a Merck team, who developed a parallel approach and published findings demonstrating the superior efficiency of bioconjugates using this technology (DOI: 10.1021/acs.bioconjchem.3c00302). This external validation not only confirms the effectiveness of our method but also positions our approach as a cutting-edge solution in the bioconjugation market, bridging the gap between existing commercial offerings.

Innovation Through Adversity

Our journey wasn't without challenges:

1. Enzyme and biologics production at our Immunobiology Laboratory
2. Analytical methods development and fine-tuning enzymatic reaction conditions at our Analytical Laboratory.
3. Heterobifunctional crosslinkers design, synthesis and purification led by our partners from Prof. Stephane Vincent’s group at the University of Namur

These obstacles pushed us to innovate, resulting in new strategies for enzyme production, bioluminescent activity assays, mass spectrometry techniques (intact mass analysis and N-glycan profiling), affinity assays (immunoreactive fraction, biolayer interferometry). Each challenge conquered has strengthened our expertise and refined our technology.

Looking Ahead

As we conclude this phase, our focus shifts to:

1. Engaging with biotech/pharma players for licensing/technology transfer
2. Optimizing and scaling up enzymes production
3. Standardizing protocols for ISO integration

We're committed to flexible collaboration models, allowing both exclusive and non-exclusive rights to parties interested in specific applications, ensuring our technology can benefit a wide range of end users.

Conclusion

The GlyPROCLICK project has not only advanced glycoprotein modification technology but also positioned Wallonia as one of the few players holding technologies in this field. Our team is poised to support future developments and collaborations, bringing this innovative technology from the lab to the market. We invite interested parties to explore how our expertise can drive their projects forward in this exciting domain.

Acknowledgements

We are grateful to the Walloon region for the funding of this research project via the Agreement #2110169 - GlyPROCLICK