{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T23:12:13Z","timestamp":1783638733665,"version":"3.55.0"},"reference-count":169,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["RS-2024-00331833"],"award-info":[{"award-number":["RS-2024-00331833"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Modernization of existing methods for the delivery of mRNA is vital in advanced therapeutics. Traditionally, mRNA has faced obstacles of poor stability due to enzymatic degradation. This work examines cutting-edge formulation and emerging techniques for safer delivery of mRNA vaccines. Inspired by the success of lipid nanoparticles (LNP) in delivering mRNA vaccines for COVID-19, a variety of other formulations have been developed to deliver mRNA vaccines for diverse infections. The meritorious features of nanoparticle-based mRNA delivery strategies, including LNP, polymeric, dendrimers, polysaccharide-based, peptide-derived, carbon and metal-based, DNA nanostructures, hybrid, and extracellular vesicles, have been examined. The impact of these delivery platforms on mRNA vaccine delivery efficacy, protection from enzymatic degradation, cellular uptake, controlled release, and immunogenicity has been discussed in detail. Even with significant developments, there are certain limitations to overcome, including toxicity concerns, limited information about immune pathways, the need to maintain a cold chain, and the necessity of optimizing administration methods. Continuous innovation is essential for improving delivery systems for mRNA vaccines. Future research directions have been proposed to address the existing challenges in mRNA delivery and to expand their potential prophylactic and therapeutic application.<\/jats:p>","DOI":"10.3390\/biom15030359","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T07:37:17Z","timestamp":1740987437000},"page":"359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Revolutionizing mRNA Vaccines Through Innovative Formulation and Delivery Strategies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1212-9667","authenticated-orcid":false,"given":"Munazza","family":"Fatima","sequence":"first","affiliation":[{"name":"Department of Microbiology, Gachon University College of Medicine, Incheon 21936, Republic of Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"An","sequence":"additional","affiliation":[{"name":"Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2054-7014","authenticated-orcid":false,"given":"Kee-Jong","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Gachon University College of Medicine, Incheon 21936, Republic of Korea"},{"name":"Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Korea mRNA Vaccine Initiative, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/190576a0","article-title":"An unstable intermediate carrying information from genes to ribosomes for protein synthesis","volume":"190","author":"Brenner","year":"1961","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7057","DOI":"10.1093\/nar\/12.18.7057","article-title":"Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs","volume":"12","author":"Krieg","year":"1984","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","article-title":"Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA","volume":"23","author":"Kariko","year":"2005","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41541-017-0032-6","article-title":"Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines","volume":"2","author":"Lutz","year":"2017","journal-title":"NPJ Vaccines"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1038\/mt.2015.103","article-title":"Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals","volume":"23","author":"Thess","year":"2015","journal-title":"Mol. 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