Delivering mRNA to Secondary Lymphoid Tissues by Phosphatidylserine-loaded Lipid Nanoparticles.

Lipid nanoparticles (LNPs) are one of the most successful technologies in mRNA delivery. While the liver has been the most frequent target for LNP delivery of mRNA, technologies for delivering mRNA molecules to extrahepatic tissues are also important. Herein, we report on the development of a LNP that targets secondary lymphoid tissues. We designed new types of alcohol-soluble phosphatidylserine (PS) derivatives as materials which target immune cells, and then incorporated them into LNPs using a microfluidic technique with a high degree of scalability and reproducibility. The resulting LNP that contained the synthesized PS delivered mRNA to the spleen much more efficiently compared to a control LNP. A sub-organ analysis revealed that the PS-loaded LNP was extensively taken up by tissue-resident macrophages in the red pulp and the marginal zone of the spleen. Thus, the PS-loaded LNP reported in this study would be a promising strategy for clinical applications that involve delivering mRNA to the spleen. This article is protected by copyright. All rights reserved.