Author: Eleanor Rockey

 Photo by: Pavel Danilyuk from Pexels

Pre-eclampsia is a potentially life-threatening hypertensive disorder which affects 3-8% of pregnancies worldwide. The early stages of the disease are characterised by impaired remodelling of spiral arteries (blood vessels supplying the placenta), resulting in their failure to develop and function properly. Impaired remodelling can reduce oxygen delivery to the placenta, causing placental stress and the release of antiangiogenic factors, proteins that inhibit blood vessel growth. These factors can induce hypertension, and disease progression can result in organ damage, seizures and stillbirth. While this disorder is still a leading cause of maternal and fetal mortality, it remains difficult to treat due to heterogeneous presentation between affected individuals and a limited understanding of its complex pathophysiology. Additionally, it is a multi-factorial disease, influenced by genetic, environmental and immunological factors. Due to the complexity of the disorder, current non-operative treatments for pre-eclampsia aim to manage symptoms rather than cure the disorder, and so it is highly desirable to design a treatment that could slow disease progression.  

Recent advancements in messenger RNA (mRNA) technology have led to applications in oncology and infectious disease prevention, most notably the Pfizer-BioNTech and Moderna COVID-19 vaccines. mRNA is a molecule that carries genetic instructions from DNA, allowing cells to produce specific proteins. In 1990, it was observed that the injection of mRNA strands into mice can result in the expression of the protein encoded within the strand. Since then, scientists have been developing ways to deliver mRNA into cells so that the cells can produce proteins that perform a desired therapeutic function. 

In women with pre-eclampsia, an antiangiogenic factor called sFlt-1 reduces the activity of vascular endothelial growth factor (VEGF), a protein which normally stimulates blood vessel growth. If placental cells can be prompted to produce more VEGF using mRNA technology, blood vessel growth could potentially be restored. 

The biggest challenge, however, is delivering the therapeutic mRNA to the placenta safely and efficiently. Therapeutic mRNA is usually delivered by tiny vehicles called lipid nanoparticles (LNPs), which are composed of a mixture of compounds called lipids. The LNPs encapsulate the mRNA and preferentially deliver it to liver cells. Delivery to the liver is driven by Apolipoprotein E (ApoE), a protein that naturally coats the LNPs when they enter the bloodstream. ApoE is recognised by specific receptors on the surface of liver cells, facilitating the uptake of nanoparticles into the cells. 

A recent study by Swingle et al. aimed to optimise the delivery of VEGF mRNA to the placenta by modifying the LNP composition. Using pregnant mice, the scientists identified an LNP composition which resulted in increased VEGF mRNA delivery to the placenta, labelled LNP 55. This LNP also reduced maternal blood pressure in mouse models of pre-eclampsia. The authors of the study suggest that the preferential placental delivery of LNP 55 is mediated by the interaction between the LNPs and a protein called β2-glycoprotein I (β2-GPI). While further research is required to confirm this mechanism, LNP 55 represents a promising approach for placental VEGF mRNA delivery. However, because pre-eclampsia is a multifactorial disorder involving numerous interacting biological pathways, targeting VEGF alone may not fully address the disease. Additionally, it would be important for future work to consider indirect effects of LNP mRNA therapy before it is used to treat this hypertensive disorder.

LNP mRNA delivery remains an exciting and innovative area of research. Studies focused on targeting mRNA therapy to different organs, such as the placenta, are also improving our understanding of the mechanisms by which LNPs deliver their cargo. Notably, recent work has been directed to investigating the role of proteins which coat LNPs, such as ApoE. Different proteins can diversely impact LNP stability and influence cell-specific targeting. Understanding how LNPs could interact with proteins in the bloodstream may help scientists design even more effective delivery systems. 

The identification of LNP 55 and fresh insights into LNP cell-specificity offer hope that mRNA technology could provide effective treatments for expectant mothers suffering from pre-eclampsia, alongside numerous other diseases.

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Article written by Eleanor Rockey, a Biochemistry student at The University of Edinburgh.

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Article edited by Priscilla Wong, a recent BSc Biological Sciences (Immunology) graduate from the University of Edinburgh and Online News Editor for EUSci.

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References:

Dimitriadis, E. et al. (2023) ‘Pre-eclampsia’ Nature Reviews Disease Primers, 9(1). doi:10.1038/s41572-023-00425-6. 

Martini, C. et al. (2025) ‘Preeclampsia: Insights into pathophysiological mechanisms and preventive strategies’, American Journal of Preventive Cardiology, 23, p. 101054. doi:10.1016/j.ajpc.2025.101054. 

Roberts, J. M., & Bell, M. J. (2013). ‘If we know so much about preeclampsia, why haven’t we cured the disease?’ Journal of reproductive immunology, 99(1-2), p. 1–9. doi:https://doi.org/10.1016/j.jri.2013.05.003

Swingle, K.L. et al. (2025) ‘Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia’, Nature, 638(8051). doi:10.1038/s41586-025-08605-y. 

Voke, E. et al. (2025) ‘Protein corona formed on lipid nanoparticles compromises delivery efficiency of mRNA cargo’, Nature Communications, 16(1). doi:10.1038/s41467-025-63726-2. 

Wang, J. et al. (2024) ‘Recent advances in lipid nanoparticles and their safety concerns for mRNA delivery’, Vaccines, 12(10), p. 1148. doi:10.3390/vaccines12101148. 

World Health Organisation (2025) Pre-eclampsia. Available at: https://www.who.int/news-room/fact-sheets/detail/pre-eclampsia (Accessed: 23 June 2026).