RNA origami nanostructures for potent and safe anti-cancer immunotherapy

Abstract Nucleic acids released from microorganisms or damaged cells are perceived by the host cells as danger signals. They can be recognized by various types of pattern recognition receptors (PRRs), leading to activation of the innate immunity. Recently, we have identified a novel self-assembled RNA-origami nanostructure that shows high structural stability, feasibility of manufacture in large quantities, and demonstrates potent innate stimulatory activity. We further test its activity in murine tumor models both in vitro and in vivo. Although this RNA-origami nanostructure exerts no direct cytotoxicity on the tumor cells, it induces significant delay or regression of tumor growth in tumor-bearing mice with minimal toxicity. The mice showing tumor regression developed systemic long-term immunity and became resistant to further challenges of tumor cells. This anti-tumor immunity is dependent on both the innate and adaptive immune system. Thus, RNA-origami nanostructures represent a new line of platforms for rational design and construction of effective, safe and affordable immunotherapeutics.