High-Throughput In Vivo Screening Identifies Differential Influences on mRNA Lipid Nanoparticle Immune Cell Delivery by Administration Route

High-throughput screening identified liposome formulations that enhance immune cell uptake and mRNA translation.

• Differential uptake of lipid nanoparticles (LNPs) by immune populations was observed depending on the injection route, either intramuscular or intravenous.
• One LNP formulation led to substantial mRNA translation in the spleen and lymph nodes, showing a more favorable biodistribution compared to a clinical standard formulation.
• Certain LNPs demonstrated strong immune transfection in the spleen and peripheral blood, with specific formulations effectively transfecting splenic dendritic cells and circulating monocytes.
• The findings suggest that LNP design criteria derived from screening could inform future mRNA vaccine and immunotherapy development.

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