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Ionizable lipids are among the essential components of LNPs, as they play crucial roles in encapsulating mRNA and facilitating its release into the cytosol. In this study, 17 innovative ionizable lipids using vitamin B5 are designed as the core structure, aiming to reduce toxicity, to maintain vaccine efficiency, and to ensure synthetic feasibility. The top\u2010performing LNP in terms of mRNA vaccine delivery in the mouse model is LNP <jats:bold>5097<\/jats:bold>, which is generated by incorporating ionizable lipid <jats:bold>I97<\/jats:bold>. mRNA\u2282LNP <jats:bold>5097<\/jats:bold> demonstrates favorable structural and physicochemical properties, high mRNA transfection efficiency, and long\u2010term stability. Moreover, mRNA\u2282LNP <jats:bold>5097<\/jats:bold> specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1\/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity. The findings here suggest the high utility of LNP <jats:bold>5097<\/jats:bold>, which includes novel vitamin B5\u2010derived ionizable lipids with reduced toxicity, in mRNA vaccine research for both infectious diseases and cancer.<\/jats:p>","DOI":"10.1002\/adhm.202403366","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T04:41:07Z","timestamp":1730868067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel Less Toxic, Lymphoid Tissue\u2010Targeted Lipid Nanoparticles Containing a Vitamin B5\u2010Derived Ionizable Lipid for mRNA Vaccine Delivery"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-2517","authenticated-orcid":false,"given":"Soyeon","family":"Yoo","sequence":"first","affiliation":[{"name":"Brain Technology Research Center Brain Science Research Division Korea Institute of Science and Technology  5 Hwarang\u2010ro 14\u2010gil, Seongbuk\u2010gu Seoul 02792 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9181-9262","authenticated-orcid":false,"given":"Muhammad","family":"Faisal","sequence":"additional","affiliation":[{"name":"Brain Technology Research Center Brain Science Research Division Korea Institute of Science and Technology  5 Hwarang\u2010ro 14\u2010gil, Seongbuk\u2010gu Seoul 02792 Republic of Korea"},{"name":"Division of Bio\u2010Medical Science &amp; 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