Gene therapy in preeclampsia: the dawn of a new era

ABSTRACT

Preeclampsia is a severe complication of pregnancy, affecting an estimated 4 million women annually. It is one of the leading causes of maternal and fetal mortality worldwide, and it has life-long consequences. The maternal multisystemic symptoms are driven by poor placentation, which causes syncytiotrophoblastic stress and the release of factors into the maternal bloodstream. Amongst them, the soluble fms-like tyrosine kinase-1 (sFLT-1) triggers extensive endothelial dysfunction by acting as a decoy receptor for the vascular endothelial growth factor (VEGF) and the placental growth factor (PGF). Current interventions aim to mitigate hypertension and seizures, but the only definite treatment remains induced delivery. Thus, there is a pressing need for novel therapies to remedy this situation. Notably, CBP-4888, a siRNA drug delivered subcutaneously to knock down sFLT1 expression in the placenta, has recently obtained Fast Track approval from the Food and Drug Administration (FDA) and is undergoing a phase 1 clinical trial. Such advance highlights a growing interest and significant potential in gene therapy to manage preeclampsia. This review summarizes the advances and prospects of gene therapy in treating placental dysfunction and illustrates crucial challenges and considerations for these emerging treatments.

GRAPHICAL ABSTRACT

KEYWORDS:

• Gene therapy
• preeclampsia
• trophoblast
• sFLT-1
• nanotechnology

Acknowledgments

We gratefully acknowledge the financial support provided to our research projects by the FNRS (Fonds de la Recherche Scientifique - National Fund for Scientific Research). We also thank the Chinese Research Council (CSC) and the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA) for supporting our fellows (F.S., M.P., A.C.). We extend our appreciation to the private charities Fondation Saint-Luc, Fetus for Life, and Vocatio for their ongoing commitment to young researchers and advancing scientific research.

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Data availability statement

The authors confirm that the data supporting the findings of this study are available in the cited articles.

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Funding

The author(s) reported there is no funding associated with the work featured in this article.