DNA-nanobody agents to interrogate and manipulate immune cell interfaces – DNAnobodies

The objective of this project is to design, characterise and functionally test new nanoscale agents based on single domain antibodies (nanobodies, Nbs), coupled to DNA scaffolds (DNAnobodies) for applications in immunology. The function of immune cells is tightly regulated by biomolecular recognition and signaling at cell-cell contacts, but emergent factors like geometry, multivalency and mechanical forces intervening at this interface are still poorly understood. The multiscale structures from single ligand-receptor bonds to supramolecular architectures, as well as the entanglement of biochemical and physical mechanisms at the nanoscale render functional studies difficult and the design of new therapeutic agents targeting this interface haphazard. We hypothesize that new nanotools are required to advance knowledge in those fields. DNAnobodies will help systematise fundamental studies as well as therapeutic design, since they offer a high control of specificity, reactivity, stoichiometry, architecture, and mechanics at the immune cell surface. This new family of hybrid nano-objects has a great potential for applications in both fundamental biology and therapeutics.