Complex carbohydrates (CC) are relevant ligands for enhancing the pharmacological properties of proteins, inducing specific cellular responses, and enabling targeted delivery in biotherapies. As such, there is a strong interest in developing a rapid method for introducing CC, complementing current enzymatic or metabolic engineering approaches. Recently, we developed an innovative electrochemical bioconjugation method that allows the specific grafting of a chemical anchor derived from N-methylluminol (NML) onto the tyrosine residues of proteins by applying an electrical potential difference in solution. This electro-bioconjugation reaction occurs within minutes, enabling the functionalization of viral vectors, bacteria, and cells without compromising their viability.
The ELEC-TRICK project will leverage this methodology to graft CC onto proteins and modify the surface of adeno-associated viruses (rAAV) used in gene therapy, as well as immune cells (T lymphocytes or Natural Killer cells) employed in cell therapies. The approach will involve designing bifunctional anchors capable of directly reacting with non-functionalized CC. These CC-NML anchors can then be activated by electrodes immersed in the substrate solution, allowing for rapid and in situ grafting of CC onto peptides and proteins. Finally, through a highly complementary interdisciplinary consortium, we will demonstrate that selected and therapeutically relevant CC-NML can be grafted onto recombinant adeno-associated viruses (rAAV) and immune cells, thereby improving their tropism and efficacy in vivo. This final step could open significant avenues in the fields of chemical biology and targeted biotherapies.
