Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 145, Issue 8, Pages 4691-4706Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.2c12893
Keywords
-
Categories
Ask authors/readers for more resources
This study developed ionizable lipid nanoparticles (LNPs) for mRNA delivery to the placenta to regulate placental vasodilation. By designing a combination of ionizable lipids, a lead LNP was identified that can deliver mRNA to trophoblasts, endothelial cells, and immune cells in the placenta. Injection of LNPs encapsulated with VEGF-A mRNA resulted in placental vasodilation, demonstrating the potential of mRNA LNPs for protein replacement therapy to treat placental disorders during pregnancy.
Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nonviral platform for mRNA delivery. While they have been explored for applications including vaccines and gene editing, LNPs have not been investigated for placental insufficiency during pregnancy. Placental insufficiency is caused by inadequate blood flow in the placenta, which results in increased maternal blood pressure and restricted fetal growth. Therefore, improving vasodilation in the placenta can benefit both maternal and fetal health. Here, we engineered ionizable LNPs for mRNA delivery to the placenta with applications in mediating placental vasodilation. We designed a library of ionizable lipids to formulate LNPs for mRNA delivery to placental cells and identified a lead LNP that enables in vivo mRNA delivery to trophoblasts, endothelial cells, and immune cells in the placenta. Delivery of this top LNP formulation encapsulated with VEGF-A mRNA engendered placental vasodilation, demonstrating the potential of mRNA LNPs for protein replacement therapy during pregnancy to treat placental disorders.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available