Our laboratory has developed a novel RNA-Nanoparticle (RNA-NP) vaccine against cancer that generates a strong innate immune activation through type 1 interferons that result in adaptive anti-tumor immunity; however, the exact mechanism of action is unclear and anti-tumor efficacy needs to be improved. The goals of this project are to elucidate the molecular mechanism of innate immune activation of our vaccine as well as to modify the RNA design and payload to improve anti-tumor efficacy.