{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:52:35Z","timestamp":1789116755743,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["NWA.1389.20.096"],"award-info":[{"award-number":["NWA.1389.20.096"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>RNA\u2010based medicinal products represent a promising frontier in personalised medicine, offering sequence\u2010specific disease targeting at various molecular levels, yet their clinical translation in the European Union (EU) may be hindered by regulatory uncertainty around definitions and evidence requirements; this study therefore aims to identify commonalities and differences in scientific and clinical characteristics of RNA\u2010based therapeutics assessed by the European Medicines Agency to inform a classification framework supporting regulatory clarity and product development. A qualitative document analysis was conducted on 13 RNA\u2010based therapeutics for non\u2010infectious diseases that applied for EU marketing authorisation by March 2025, using EU regulatory documents including European Public Assessment Reports and Risk Management Plans to analyse descriptive, scientific and clinical characteristics, with data extraction validated via a dual\u2010review process. Of the 13 products, 10 were approved, two refused and one withdrawn; they included five siRNAs, seven antisense oligonucleotides (ASOs) and one aptamer, primarily for rare diseases, with 12 acting through sequence\u2010specific hybridisation to pre\u2010mRNA or mRNA to suppress or modify protein production, often targeting liver diseases using delivery systems like GalNAc conjugation or lipid nanoparticles, while clinical challenges included limited efficacy data (e.g. small trials, surrogate endpoints) and recurring safety concerns including coagulation\u2010related risks for ASOs, and notably risk profiles were not consistently linked to disease targets or RNA sequence. These findings highlight an opportunity for classification based on RNA mechanism and related chemical modifications conveying similar regulatory implications, suggesting that a structured framework could support knowledge pooling, which is especially useful for rare disease indications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70577","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:31:23Z","timestamp":1778736683000},"source":"Crossref","is-referenced-by-count":1,"title":["Decoding RNA regulation: Challenges and opportunities for RNA\u2010based therapies in Europe"],"prefix":"10.1002","author":[{"given":"Olivia C.","family":"Lewis","sequence":"first","affiliation":[{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science Utrecht University  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Leopold","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science Utrecht University  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce M.","family":"Hoek","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science Utrecht University  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond M.","family":"Schiffelers","sequence":"additional","affiliation":[{"name":"CDL Research University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L.","family":"De Bruin","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science Utrecht University  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.11.011"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102019\u2010318269"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202300633"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052736"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10374"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573\u2010024\u201000070\u2010y"},{"key":"e_1_2_9_9_1","unstructured":"European Parliament Council of the European Union.Regulation (EC) No 1394\/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001\/83\/EC and Regulation (EC) No 726\/2004. 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