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Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation.
Yu, Haitao; Angelova, Angelina; Angelov, Borislav; Dyett, Brendan; Matthews, Lauren; Zhang, Yiran; El Mohamad, Mohamad; Cai, Xudong; Valimehr, Sepideh; Drummond, Calum J; Zhai, Jiali.
Afiliación
  • Yu H; School of Science, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
  • Angelova A; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 91400, Orsay, France.
  • Angelov B; Extreme Light Infrastructure ERIC, Za Radnici 835, 25241, Dolni Brezany, Czech Republic.
  • Dyett B; School of Science, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
  • Matthews L; ESRF, The European Synchrotron, 71 avenue des Martyrs, 38043, Grenoble, France.
  • Zhang Y; School of Science, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
  • El Mohamad M; School of Science, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
  • Cai X; School of Science, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
  • Valimehr S; Ian Holmes Imaging Center, Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Parkville, Victoria 3052, Australia.
  • Drummond CJ; Australian Research Council Centre for Cryo-Electron Microscopy of Membrane Proteins, The University of Melbourne, Melbourne, Victoria 3010, Australia.
  • Zhai J; School of Science, STEM College, RMIT University, Melbourne, Victoria 3000, Australia.
Angew Chem Int Ed Engl ; 62(35): e202304977, 2023 08 28.
Article en En | MEDLINE | ID: mdl-37391876
Ionisable amino-lipid is a key component in lipid nanoparticles (LNPs), which plays a crucial role in the encapsulation of RNA molecules, allowing efficient cellular uptake and then releasing RNA from acidic endosomes. Herein, we present direct evidence for the remarkable structural transitions, with decreasing membrane curvature, including from inverse micellar, to inverse hexagonal, to two distinct inverse bicontinuous cubic, and finally to a lamellar phase for the two mainstream COVID-19 vaccine ionisable ALC-0315 and SM-102 lipids, occurring upon gradual acidification as encountered in endosomes. The millisecond kinetic growth of the inverse cubic and hexagonal structures and the evolution of the ordered structural formation upon ionisable lipid-RNA/DNA complexation are quantitatively revealed by in situ synchrotron radiation time-resolved small angle X-ray scattering coupled with rapid flow mixing. We found that the final self-assembled structural identity, and the formation kinetics, were controlled by the ionisable lipid molecular structure, acidic bulk environment, lipid compositions, and nucleic acid molecular structure/size. The implicated link between the inverse membrane curvature of LNP and LNP endosomal escape helps future optimisation of ionisable lipids and LNP engineering for RNA and gene delivery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Nucleicos / Nanopartículas / COVID-19 Límite: Humans Idioma: En Revista: Angew Chem Int Ed Engl Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Nucleicos / Nanopartículas / COVID-19 Límite: Humans Idioma: En Revista: Angew Chem Int Ed Engl Año: 2023 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania