(30q) Lipid Nanoparticle Structure and Immune Response Regulate mRNA Organ Tropism and Pup Growth during Pregnancy in Mice.

Treating pregnancy-related disorders is challenging because many relevant medications cause maternal and fetal toxicity. This potential danger has hindered drug development for pregnancy-related disorders for several decades. Lipid nanoparticle (LNP)-based RNA therapies with high delivery efficacy and favorable safety profile can quell toxicity concerns. To this extent, we report LNP structures that effectively deliver mRNA to maternal organs and placenta with no fetal delivery. In the placenta, LNPs transfect trophoblasts, endothelial cells, and immune cells. Additionally, we show that immune response during pregnancy alter LNP organ tropism and hinder pup growth. Together, our results identify potent LNP structures and design criteria for safe mRNA delivery during pregnancy.