{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:49:56Z","timestamp":1792709396565,"version":"4.5.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":99,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LQ24H120006"],"award-info":[{"award-number":["LQ24H120006"]}]},{"DOI":"10.13039\/501100007194","name":"Wenzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["Y2023799"],"award-info":[{"award-number":["Y2023799"]}],"id":[{"id":"10.13039\/501100007194","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lipid nanoparticles (LNPs) are critical for the delivery of drugs and nucleic acids. However, current mRNA-LNP formulations require stringent freezing for storage, which limits their global distribution. Our previous studies demonstrated that optimizing the lipid type or molar ratio of Comirnaty-type mRNA-LNPs could enhance their lyophilization stability, thus improving their long-term storage stability under mild conditions. This study aims to enhance the storage stability of Spikevax-type mRNA-LNPs by optimizing lipid compositions and utilizing lyophilization for storage at 4\u00b0C. Fifteen mRNA-LNP formulations were evaluated for their physicochemical properties and transfection efficiency (TE) in human embryonic kidney (HEK)-293T cells using the I-optimal design of mixture experiments. Mathematical models were developed to predict the relationships among encapsulation efficiency, transfection performance and lipid ratios. The optimized mRNA-LNP formulation (N4), with a 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-to-cholesterol ratio of 0.36, exhibited superior stability and TE after lyophilization. N4 outperformed the original Spikevax formulation in several cell lines, including eye-derived ARPE-19 cells and lung-derived A549 cells. In vivo, N4 demonstrated high TE in the spleen of C57BL\/6 mice both before and after lyophilization, with no signals observed in the kidneys, heart or eyes. These findings suggest that the optimized N4 formulation offers a robust, stable and efficient delivery system for gene therapy and vaccines, potentially overcoming the storage limitations of current Spikevax-type mRNA-LNPs and broadening their therapeutic applications.<\/jats:p>","DOI":"10.1093\/rb\/rbaf023","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T08:46:02Z","timestamp":1744101962000},"source":"Crossref","is-referenced-by-count":14,"title":["Development of lyophilized mRNA-LNPs with high stability and transfection efficiency in specific cells and tissues"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0961-8224","authenticated-orcid":false,"given":"Ting","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang 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