(558d) Functionalizing DNA Nanostructures for Vaccine and Therapeutic Materials Design

The careful engineering of soft materials at the nanoscale has led to the clinical translation of medicines for cancers, genetic disorders, and infectious diseases. However, the scope, manufacturability, and safety of current clinical delivery platforms remain unknown. DNA nanostructures are considered to be a next-generation biomedical nanomaterial due to their control over 1) size and shape; 2) immunogenicity; 3) targeting ligands and payload. Here, we describe our advances towards functional nanostructures via the covalent functionalization of wireframe DNA origami nanostructures. We first introduce a new liquid chromatography analytical technique for monitoring reactions that occur on DNA nanostructures. Then, we demonstrate the covalent functionalization, using strain-promoted alkyne-azide cycloaddition (SPAAC) click chemistry, of biomedically relevant conjugates, namely: proteins, polymers, peptides, carbohydrates, and small molecules. Finally, we investigate the functionality of these new materials. We investigate the potential for covalent PEGylation of DNA nanostructures to protect against nuclease degradation. We additionally demonstrate the early activation of B cells when presented with DNA nanostructures scaffolding a clinically relevant HIV immunogen. Future work will investigate this material class’s ability to delivery payloads to specific organs and cell types, while evaluating its immunotoxicity in animal models.