ORBIT · Elucidating the nano-biointeractions on DNA origami

The forces governing the nano-biointeractions are essential to understand the biological behaviour and pharmacokinetics of the nanostructures. So far, these understandings have been limited to nanoparticles. However, it should be noted that the NPs chemical synthetic methods render non-homogeneous dispersions, even when low polydispersity is reached. In addition, the modification of NPs with a specific number of ligands is still challenging and there is no agreement about the most effective configuration or number of ligands to achieve efficient targeting in vivo. The programmability of the DNA-nanostructures (origamis) allows the synthesis of predictable and controllable sizes and shapes with almost atomic precision. In addition, the origamis can also be designed to include additional molecules, with high accuracy on the valency and the orientation. Thus, this technology offers a powerful tool to study and understand the biological behaviour of objects at the nanoscale since precise control over the size, shape and attachment of molecules can be achieved when other methods are unable to. Based on the structural organization and spatial distribution of natural and specific bionanoparticles, such as viruses, this project will exploit the atomic programmability of origamis to design a library of DNA nanostructures inspired on viral particles. The biomolecular corona will be studied to understand its impact on origamis biodistribution, a topic still not studied yet. Finally, the cell response will be evaluated in terms of targeting and immune response. These results will help to a better understanding of the mechanism between nano-structures and living systems and to formulate guidelines to synthesize more efficient nanomedicines. Overall, this project will allow me to carry out a 2-year project independently, growing towards a mature, professional and independent researcher in the DNA nanotechnology field, reinforcing my expertise on the nanomedicine field.