NanoReady: A ready-made DC-selective delivery platform for personalized mRNA cancer vaccines with strong NHP immunogenicity.

NanoReady is a next-generation mRNA delivery platform designed to overcome the limitations of conventional lipid-based systems, such as lipid nanoparticles (LNP) and Lipoplex (LPX), particularly for personalized cancer vaccines. It combines a novel cationic lipid with a biodegradable polymer, forming a stable nanoparticle that efficiently encapsulates mRNAs with a wide range of lengths. NanoReady nanoparticles can be pre-assembled without RNA as a ready-made formulation, and upon availability of patient-specific antigen-encoding mRNA, NanoReady rapidly incorporates the RNA to form uniform, administration-ready particles. NanoReady selectively delivers antigen mRNA to professional antigen-presenting cells, particularly dendritic cells in the spleen, where robust antigen-specific T-cell responses are elicited. When combined with mRNA, NanoReady forms multilamellar nanoparticles that exhibit high mRNA loading capacity and efficient endosomal release, leading to enhanced protein expression. As a result, it induces strong T-cell immune responses to the encoding antigen that overcomes immune tolerance when encoding self-antigens. In B16-F10 tumor mouse model, NanoReady mRNA vaccine encoding the self-antigen mTRP2 induced potent CD8 T-cell responses, resulting in significant tumor growth suppression and improved survival. Compared to DOTMA based LPX formulations, NanoReady achieved markedly higher antigen expression, stronger antigen-specific T cell immunogenicity, and superior anti-tumor efficacy. Importantly, a pilot non-human primate (NHP) study demonstrated antigen-specific T-cell immunogenicity following NanoReady-mRNA vaccination, supporting translational potential. Furthermore, repeated administration of NanoReady-mRNA vaccine showed no toxicity in various animal models confirming the platform's high biocompatibility and safety. These findings highlight NanoReady as a promising platform for personalized cancer vaccines, combining high mRNA delivery efficiency, robust immune response, and excellent safety.