Immune pathways are prime examples of cascades where a finely balanced sequence of interactions decides between life-changing outcomes, varying from tolerance to active fight. Immune-modulating materials, therefore, would uniquely benefit from precision control over functionality. DNA-based nanomaterials have the potential to change our current bioengineering standards due to their inherent architectural uniformity and nanometer control of functionalization, allowing for a quantitative analysis of material parameters on cell activation. We use structural geometry of DNA-based materials to provoke controlled intracellular manipulation of immune signaling via the hierarchical and spatial organization of constitutive DNA binding proteins.
The programmability of DNA as a biomaterial is exploited in the “DNA origami” technique for engineering self-assembling nanostructures with an unprecedented level of uniformity in size and spacing of ligand presentation. The control of ligand positioning with nanoscale precision is a potent tool to investigate ligand receptor interactions. In particular, DNA origami nanoparticles mimicking viruses in size and shape are designed to study dendritic cell activation and the immune response. Understanding the best spacing of ligands for the activation of the dendritic cells constitutes an essential feature for the development of vaccines with enhanced potency and specificity.
Comberlato, K. Paloja, M.M.C. Bastings; Nucleic acids presenting polymer nanomaterials as vaccine adjuvants, RSC Journal of Materials Chemistry B, 2019, DOI: 10.1039/C9TB01222B, Emergent Investigators Edition,