Engineering protein-conjugated lipid nanoparticles for targeted mRNA delivery to the placenta

Introduction: A major challenge of lipid nanoparticles (LNPs) as an in vivo nucleic acid delivery platform is the fact that LNPs primarily accumulate in the liver following systemic administration, limiting their success to liver-centric conditions. Here, we engineer protein-conjugated LNPs to achieve targeted, extrahepatic messenger RNA (mRNA) delivery to the placenta to treat placental disorders. We evaluate how choice of targeting protein effects LNP targeting efficacy, route of LNP endocytosis, and LNP immunogenicity during pregnancy.