{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:49:57Z","timestamp":1792709397587,"version":"4.5.0"},"reference-count":88,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["RGPIN-2021-02691"],"award-info":[{"award-number":["RGPIN-2021-02691"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RGPIN-2021-02691"],"award-info":[{"award-number":["RGPIN-2021-02691"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chair","doi-asserted-by":"publisher","award":["CRC-240394"],"award-info":[{"award-number":["CRC-240394"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CRC-240394"],"award-info":[{"award-number":["CRC-240394"]}],"id":[{"id":"https:\/\/ror.org\/0517h6h17","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010785","name":"Canada First Research Excellence Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010785","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01ktx4s83","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Canada Biomedical Research Fund","doi-asserted-by":"publisher","award":["CBRF-2-2023-00072"],"award-info":[{"award-number":["CBRF-2-2023-00072"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Messenger RNA-lipid nanoparticle (mRNA-LNP)-based drug products represent a promising platform for prophylactic and therapeutic applications. However, their limited stability poses significant challenges for storage and global distribution. The instability of mRNA-LNP products makes them dependent on ultra-cold chain systems. This instability is driven by various physicochemical factors, including temperature, pH, light exposure, oxidation, aggregation, shear stress, and humidity. These factors destabilize the physical and chemical integrity of both mRNA and lipid nanoparticle (LNP) components, leading to reduced vaccine potency and potentially increasing the risk of adverse safety outcomes. Understanding these factors and their mechanisms is crucial for retaining mRNA-LNP efficacy. This review discusses the key physicochemical instability factors and molecular degradation mechanisms responsible for the structural and functional deterioration of mRNA-LNP formulations. Further, we summarize the stabilization strategies and analytical methods used to detect and quantify the degradation of mRNA-LNP products. Addressing these challenges is critical for advancing next-generation nucleic acid-based drug products and LNP-based delivery systems.<\/jats:p>","DOI":"10.3390\/vaccines14070620","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:29:39Z","timestamp":1784100579000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Possible Mechanisms of mRNA-LNP Degradation: A Comprehensive Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7152-0468","authenticated-orcid":false,"given":"MD Faizul Hussain","family":"Khan","sequence":"first","affiliation":[{"name":"Viral Vectors and Vaccines Bioprocessing Group, Department of Bioengineering, McGill University, Montreal, QC H3A 0G4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahsina","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Jahangirnagar University, Dhaka 1342, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2520-7401","authenticated-orcid":false,"given":"Abhishek","family":"Mishra","sequence":"additional","affiliation":[{"name":"Viral Vectors and Vaccines Bioprocessing Group, Department of Bioengineering, McGill University, Montreal, QC H3A 0G4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9110-8815","authenticated-orcid":false,"given":"Amine A.","family":"Kamen","sequence":"additional","affiliation":[{"name":"Viral Vectors and Vaccines Bioprocessing Group, Department of Bioengineering, McGill University, Montreal, QC H3A 0G4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.ymthe.2019.02.012","article-title":"Delivering the Messenger: Advances in Technologies for Therapeutic MRNA Delivery","volume":"27","author":"Kowalski","year":"2019","journal-title":"Mol. 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