Non-Viral RNA Delivery During Pregnancy: Opportunities and Challenges

During pregnancy, the risk of maternal and fetal adversities increases due to physiological changes, genetic predispositions, environmental factors, and infections. Unfortunately, treatment options are severely limited because many essential interventions are unsafe, inaccessible, or lacking in sufficient scientific data to support their use. One potential solution to this challenge may lie in emerging RNA therapeutics for gene therapy, protein replacement, maternal vaccination, fetal gene editing, and other prenatal treatment applications. In this review, the current landscape of RNA platforms and non-viral RNA delivery technologies that are under active development for administration during pregnancy is explored. Advancements of pregnancy-specific RNA drugs against SARS-CoV-2, Zika, influenza, preeclampsia, and for in-utero gene editing are discussed. Finally, this study highlights bottlenecks that are impeding translation efforts of RNA therapies, including the lack of accurate cell-based and animal models of human pregnancy and concerns related to toxicity and immunogenicity during pregnancy. Overcoming these challenges will facilitate the rapid development of this new class of pregnancy-safe drugs.