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Interest in mRNA vaccines and therapeutic drugs continues to grow. Although lipid nanoparticles (LNP) formulations are effective for infectious disease immunity, the lipid nanoparticles (LNP) formulations used for other mRNA delivery applications have limitations such as off-target accumulation, poor immune transfection, and immunogenicity, which restrict their application in immunological engineering. The development of new mRNA has historically had a low throughput due to its reliance on low plex measurements and is severely limited by the discovery process of LNP. We have developed a high-throughput in vivo mRNA LNP screening platform based on bar-shaped mRNA (b-mRNA). Using this b-mRNA screening platform to simultaneously evaluate 122 LNP, we identified a new LNP formulation with efficient extrhepatic transfection ability. We evaluated a lead LNP candidate for in situ immune modulation, which performed well in a melanoma homologous mouse model. The results showed that compared with mice treated with the gold standard mRNA LNP formulation, the tumor burden was significantly reduced and the survival period was prolonged. We used a new biochemical characterization technique to analyze the formation of protein caps on nanoparticles at single-particle resolution, to understand the impact of protein adsorption on transfection in the liver and spleen. Our research results collectively demonstrate the value of advanced LNP screening and characterization techniques in the development of the next generation of mRNA immunological engineering. This study was published in Advanced Materials under the title "High-Throughput In Vivo Screening Using Barcoded mRNA Identifies Lipid Nanoparticles with Extrahepatic Tropism for In Situ Immunoengineering".
References:
DOI: 10.1002/adma.202514370
