The rapid development of messenger RNA(mRNA)vaccines formulated with lipid nanoparticles(LNPs)has contributed to control of the COVID-19 pandemic.However,mRNA vaccines have raised concerns about their potential toxici...The rapid development of messenger RNA(mRNA)vaccines formulated with lipid nanoparticles(LNPs)has contributed to control of the COVID-19 pandemic.However,mRNA vaccines have raised concerns about their potential toxicity and clinical safety,including side effects,such as myocarditis,anaphylaxis,and pericarditis.In this study,we investigated the potential of trehalose glycolipids-containing LNP(LNP S050L)to reduce the risks associated with ionizable lipids.Trehalose glycolipids can form hydrogen bonds with polar biomolecules,allowing the formation of a stable LNP structure by replacing half of the ionizable lipids.The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity,respectively.Furthermore,mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity,including in the heart,spleen,and liver,while sustaining gene expression and immune efficiency,compared to conventional LNPs(Con-LNPs).Our findings suggest that LNP S050L,a trehalose glycolipid-based LNP,could facilitate the development of safe mRNA vaccines with improved clinical safety.展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.NRF-2021M3E5E3080563,RS-2023-00229101)the Ministry of Food and Drug Safety(No.22213MFDS421)+4 种基金the Korea Institute of Science and Technology(KIST)Institutional Program(No.2E32852)H.Kim was supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.RS-2023-00209955)the Korea Institute of Science and Technology(KIST)Institutional Program(No.2E33111)J.H.Nam was supported by grants from the Ministry of Food and Drug Safety(grant number 22213MFDS421)partially supported by the Brain Korea 21 Four Program.H.Youn was supported by a grant from the Ministry of Food and Drug Safety(RS-2023-00217026).
文摘The rapid development of messenger RNA(mRNA)vaccines formulated with lipid nanoparticles(LNPs)has contributed to control of the COVID-19 pandemic.However,mRNA vaccines have raised concerns about their potential toxicity and clinical safety,including side effects,such as myocarditis,anaphylaxis,and pericarditis.In this study,we investigated the potential of trehalose glycolipids-containing LNP(LNP S050L)to reduce the risks associated with ionizable lipids.Trehalose glycolipids can form hydrogen bonds with polar biomolecules,allowing the formation of a stable LNP structure by replacing half of the ionizable lipids.The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity,respectively.Furthermore,mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity,including in the heart,spleen,and liver,while sustaining gene expression and immune efficiency,compared to conventional LNPs(Con-LNPs).Our findings suggest that LNP S050L,a trehalose glycolipid-based LNP,could facilitate the development of safe mRNA vaccines with improved clinical safety.
