Spherical Nucleic Acid nano-architectures as first-in-class cGAS agonists for the immunotherapeutic treatment of Glioblastoma

This grant application addresses the goal of developing novel nucleic acid-based nanoconstructs – specifically spherical nucleic acid (SNA) nanostructures – that will be poised to enter the clinic as revolutionary, cancer-targeting agents that could dramatically improve and save the lives of patients suffering from glioblastoma (GBM). Researchers in Professor Chad Mirkin’s group will primarily lead and carry out the synthesis and comprehensive physico-chemical and biological characterization of SNA nanoconjugates. Specifically, we will synthesize and evaluate a library of SNAs conjugated with interferon-stimulatory double-stranded (ISD) DNA and determine how structural characteristics of ISD oligonucleotides and their conjugation to nanoparticle cores influence activation in the Stimulator of Interferon Genes (STING) pathway. Based on these results, these structures will be investigated further in Professor Alex Stegh’s lab at Washington University in St. Louis in cell assays and GBM animal models. Together, this work will provide a better biological understanding of SNA therapeutics for cancer.