ArticleProceedings of the National Academy of Sciences of the United States of America2024
Lipid nanoparticle structure and delivery route during pregnancy dictate mRNA potency, immunogenicity, and maternal and fetal outcomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Preparation of placenta-tropic mRNA lipid nanoparticles for pregnancy disorders.Nature protocols · 2026Review
- Preparation of targeted lipid nanoparticles for precision nucleic acid delivery.Nature protocols · 2026Review
- Enhancing Lipid Nanoparticle-Mediated Circular RNA and mRNA Expression in the Placenta through Inhibition of IFNAR-JAK-STAT Signaling.Nano letters · 2026Article
- Investigating the impact of hypoxia and syncytialization on lipid nanoparticle-mediated mRNA delivery to placental cells.Bioengineering & translational medicine · 2026Article
- Spatiotemporal targeting of messenger RNA lipid nanoparticles to the endometrium for the treatment of reproductive disorders.Nature nanotechnology · 2026Article
- Enhanced Epigenetic Modulation via mRNA-Encapsulated Lipid Nanoparticles Enables Targeted Anti-inflammatory Control.ACS synthetic biology · 2026Article
- Nanotechnology for reproductive healthcare: a comprehensive review.Journal of nanobiotechnology · 2026Review
- Lipid Nanoparticle Database towards structure-function modeling and data-driven design for nucleic acid delivery.Nature communications · 2026Article
- Targeted nanoparticles for placenta-specific drug delivery in pregnant rhesus macaques.Theranostics · 2026Article
- Therapeutic nanoparticle safety in pregnancy: Bridging knowledge gaps with environmental insights and a translational roadmap.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Flow cytometric analysis of the murine placenta to evaluate nanoparticle platforms during pregnancy.Placenta · 2025Article
- Probing the Role of Lipid Nanoparticle Elasticity on mRNA Delivery to the Placenta.Nano letters · 2025Article
- Article
- Optimized strategies for precise messenger RNA delivery using site-specific lipid nanoparticle-based drug delivery systems.Nanomedicine (London, England) · 2025Article
- The role of placental hormones and metabolites in modulating uterine circulation in physiological and pathological pregnancies.Frontiers in endocrinology · 2025Review
- Review
- Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- EGFR-targeted ionizable lipid nanoparticles enhance in vivo mRNA delivery to the placenta.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Systematic development of ionizable lipid nanoparticles for placental mRNA delivery using a design of experiments approach.Bioactive materials · 2024Article
- RNA delivery systems.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Treating pregnancy-related disorders is exceptionally challenging because the threat of maternal and/or fetal toxicity discourages the use of existing medications and hinders new drug development. One potential solution is the use of lipid nanoparticle (LNP) RNA therapies, given their proven efficacy, tolerability, and lack of fetal accumulation. Here, we describe LNPs for efficacious mRNA delivery to maternal organs in pregnant mice via several routes of administration. In the placenta, our lead LNP transfected trophoblasts, endothelial cells, and immune cells, with efficacy being structurally dependent on the ionizable lipid polyamine headgroup. Next, we show that LNP-induced maternal inflammatory responses affect mRNA expression in the maternal compartment and hinder neonatal development. Specifically, pro-inflammatory LNP structures and routes of administration curtailed efficacy in maternal lymphoid organs in an IL-1β-dependent manner. Further, immunogenic LNPs provoked the infiltration of adaptive immune cells into the placenta and restricted pup growth after birth. Together, our results provide mechanism-based structural guidance on the design of potent LNPs for safe use during pregnancy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.