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Protein-based therapeutics, which account for about 30% of the new drugs approved each year, are broadening the range of treatment options. Yet their effectiveness remains limited owing to some of the structural and chemical properties specific to proteins. At INRS, Marc-André Gauthier is focused on enhancing these drugs using bioconjugation, which involves chemically modifying the therapeutic proteins to optimize their performance and tolerance by the body.

Relying on an interdisciplinary approach that merges computer models, advanced chemical analyses, cell tests and animal model trials and working in cooperation with experts in fields like chemistry, physics, engineering and biology, Professor Gauthier and his team are developing nanostructures that can modulate the activation of drug proteins. More specifically, they are creating controlled chemical bonds that can target proteins in precise areas of the body to increase a treatment’s selectivity. The strategy also makes it possible to graft polymers onto the proteins’ surface to increase their size and extend the duration of their action, thus reducing the frequency of administration to patients.

What’s more, the technique masks proteins the immune system would otherwise detect, and that helps limit allergic-type reactions.

While the research is essentially fundamental, Marc-André Gauthier is collaborating with the pharmaceutical industry to apply his discoveries to real treatments. The applications include optimized treatments for acute lymphoblastic leukemia, multispecific antibodies to fight cancer cells and innovative bioconjugates to protect brain tissue after a stroke.

References

  • Zaghmi, A., Dopico-López, A., Pérez-Mato, M., Iglesias-Rey, R., Hervella, P., Greschner, A. A., Bugallo-Casal, A., da Silva, A., Gutiérrez-Fernández, M., Castillo, J., Campos Pérez, F., & Gauthier, M. A. (2020). Sustained blood glutamate scavenging enhances protection in ischemic stroke. Communications Biology, 3, 614. https://doi.org/10.1038/s42003-020-01406-1
  • Messaoudi, S., Wai, K., Marple, A., Baniahmad, S. F., Wylie, R. G., Pelletier, M., Craig, M., Durocher, Y., Greschner, A. A., & Gauthier, M. A. (2024). Rapid systematic screening of bispecific antibody surrogate geometries for T-cell engagement using DNA nanotechnology. Journal of the American Chemical Society, 146(48), 29824–29835. https://doi.org/10.1021/jacs.4c02023
  • Kihal, N., Nguyen, P. T., Nazemi, A., Greschner, A. A., Gauthier, M. A., & Bourgault, S. (2024). DNA nanostructures prevent the formation of and convert toxic amyloid proteospecies into cytocompatible and biodegradable spherical complexes. Advanced Genetics, 5(2), Article e502. https://doi.org/10.1002/agt2.502
  • Greschner, A. A., Brahiti, N., Auger, M., Hu, L., Soleymani Abyaneh, H., Barbeau, X., Parent, V., Gaillet, B., Guay, D., Soultan, A.-H., & Gauthier, M. A. (2023). PEGylation of a peptide-based amphiphilic delivery agent and influence on protein delivery to cells. Biomacromolecules, 24(12), 4890–4900. https://doi.org/10.1021/acs.biomac.3c00815