Orthogonal Design of Experiments for Engineering of Lipid Nanoparticles for mRNA Delivery to the Placenta.

ABSTRACT: During healthy pregnancy, the placenta develops to allow for exchange of nutrients and oxygen between the mother and the fetus. However, placental dysregulation can lead to several pregnancy disorders, such as preeclampsia and fetal growth restriction. Recently, lipid nanoparticle (LNP)-mediated delivery of messenger RNA (mRNA) has been explored as a promising approach to treat these disorders. Here, iterative libraries of LNPs with varied excipient molar ratios are screened in vitro for enhanced mRNA delivery to placental cells with minimal cytotoxicity when compared to an LNP formulation with a standard excipient molar ratio. LNP C5, the top formulation identified by these screens, demonstrates a fourfold increase in mRNA delivery in vitro compared to the standard formulation. Intravenou

SUBMITTER: Safford HC 

PROVIDER: S-EPMC10837330 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature