{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:48:59Z","timestamp":1792691339191,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Drug Deliv."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Messenger RNA (mRNA) therapeutics have advanced from experimental platforms to clinical application, driven largely by the success of lipid nanoparticle (LNP)-based COVID-19 vaccines. Building on this progress, nanoparticle-mediated mRNA delivery is being extended to non-infectious indications, including oncology, autoimmune disorders, and inherited diseases. However, challenges such as extrahepatic targeting, endosomal escape, repeat\u2010dose immunogenicity, thermostability, and scalable manufacturing remain significant barriers to translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A rapid review of peer-reviewed studies and registered clinical trials published between January 2020 and October 2025 was conducted. Searches were performed in PubMed, Scopus, Web of Science Core Collection, and ClinicalTrials.gov using combined terms related to RNA modality and nanoparticle delivery. Eligible studies focused on non-viral nanoparticle platforms for therapeutic, non\u2010infectious mRNA delivery, including applications in protein replacement, genome editing, and immune modulation. Screening yielded 15 studies for inclusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LNPs remain the most clinically advanced platform for therapeutic mRNA delivery. At the same time, polymeric, peptide\u2010based, exosome-inspired, and hybrid nanoparticle systems are expanding the delivery landscape. Emerging RNA formats, including self-amplifying RNA and circular RNA, show potential to prolong expression at lower doses. Clinically, individualized mRNA neoantigen therapy (mRNA-4157\/V940) combined with pembrolizumab reduced recurrence risk by approximately 49% in high-risk melanoma in the KEYNOTE-942 phase 2b trial, supporting phase 3 development. In cystic fibrosis, inhaled CFTR mRNA (ARCT-032) advanced to phase 2 after early phase 1 data demonstrated safety and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Evidence for non-viral nanoparticle\u2010mediated mRNA therapeutics is strong in preclinical research and increasingly promising in clinical applications beyond vaccinology. While LNPs dominate current translation, alternative carriers and improved RNA formats may broaden tissue targeting and therapeutic durability. Advances in biodegradable ionisable lipids, organ-selective LNPs, and lyophilised or solid formulations are being developed to address persistent delivery and manufacturing constraints. As the field matures, regulatory and policy frameworks will need to align with therapeutic endpoints and support long-term safety monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fddev.2026.1793322","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:41:35Z","timestamp":1775022095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Nanoparticle-mediated mRNA delivery for cancer, autoimmunity, and genetic diseases: a rapid review"],"prefix":"10.3389","volume":"6","author":[{"given":"Okechukwu Paul-Chima","family":"Ugwu","sequence":"first","affiliation":[{"name":"Department of Publication and Extension, Kampala International University","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian C.","family":"Ogenyi","sequence":"additional","affiliation":[{"name":"Department of Publication and Extension, Kampala International University","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Basajja","sequence":"additional","affiliation":[{"name":"Healthcare and Data management, Leiden University","place":["Leiden, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinyere N.","family":"Ugwu","sequence":"additional","affiliation":[{"name":"Department of Publication and Extension, Kampala International University","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mundu M.","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Renewable Energy Systems, Kampala International University","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Ben","family":"Okon","sequence":"additional","affiliation":[{"name":"Department of Publication and Extension, Kampala International University","place":["Kampala, Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126183","DOI":"10.1016\/j.ijpharm.2025.126183","article-title":"Development of BMX siRNA lipid nanoparticles using novel ionizable and cleavable lipids discovered through AI and experimentation for cancer therapy","volume":"684","author":"Alasmari","year":"2025","journal-title":"Int. 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