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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\u2010viral RNA delivery technologies that are under active development for administration during pregnancy is explored. Advancements of pregnancy\u2010specific RNA drugs against SARS\u2010CoV\u20102, Zika, influenza, preeclampsia, and for in\u2010utero gene editing are discussed. Finally, this study highlights bottlenecks that are impeding translation efforts of RNA therapies, including the lack of accurate cell\u2010based 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\u2010safe drugs.<\/jats:p>","DOI":"10.1002\/smll.202306134","type":"journal-article","created":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T11:46:11Z","timestamp":1703504771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Non\u2010Viral RNA Delivery During Pregnancy: Opportunities and Challenges"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2115-7731","authenticated-orcid":false,"given":"Namit","family":"Chaudhary","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering Carnegie Mellon University  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1812-4744","authenticated-orcid":false,"given":"Alexandra N.","family":"Newby","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Carnegie Mellon University  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0100-7824","authenticated-orcid":false,"given":"Kathryn A.","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Carnegie Mellon University  Pittsburgh PA 15213 USA"},{"name":"Department of Biomedical Engineering Carnegie Mellon University  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,25]]},"reference":[{"key":"e_1_2_13_1_1","first-page":"548","volume":"90","author":"Marsh C. 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