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Role of Ionizable Lipids in SARS-CoV-2 Vaccines As Revealed by Molecular Dynamics Simulations: From Membrane Structure to Interaction with mRNA Fragments.
Paloncýová, Markéta; Cechová, Petra; Srejber, Martin; Kührová, Petra; Otyepka, Michal.
  • Paloncýová M; Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Slechtitelu 27, 779 00 Olomouc, Czech Republic.
  • Cechová P; Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Slechtitelu 27, 779 00 Olomouc, Czech Republic.
  • Srejber M; Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Slechtitelu 27, 779 00 Olomouc, Czech Republic.
  • Kührová P; Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Slechtitelu 27, 779 00 Olomouc, Czech Republic.
  • Otyepka M; Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Slechtitelu 27, 779 00 Olomouc, Czech Republic.
J Phys Chem Lett ; 12(45): 11199-11205, 2021 Nov 18.
Article in English | MEDLINE | ID: covidwho-1510547
ABSTRACT
Recent advances in RNA-based medicine have provided new opportunities for the global current challenge, i.e., the COVID-19 pandemic. Novel vaccines are based on a messenger RNA (mRNA) motif with a lipid nanoparticle (LNP) vector, consisting of high content of unique pH-sensitive ionizable lipids (ILs). Here we provide molecular insights into the role of the ILs and lipid mixtures used in current mRNA vaccines. We observed that the lipid mixtures adopted a nonlamellar organization, with ILs separating into a very disordered, pH-sensitive phase. We describe structural differences of the two ILs leading to their different congregation, with implications for the vaccine stability. Finally, as RNA interacts preferentially with IL-rich phases located at the regions with high curvature of lipid phase, local changes in RNA flexibility and base pairing are induced by lipids. A proper atomistic understanding of RNA-lipid interactions may enable rational tailoring of LNP composition for efficient RNA delivery.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Messenger / COVID-19 Vaccines / Lipids Topics: Vaccines Limits: Humans Language: English Journal: J Phys Chem Lett Year: 2021 Document Type: Article Affiliation country: Acs.jpclett.1c03109

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Messenger / COVID-19 Vaccines / Lipids Topics: Vaccines Limits: Humans Language: English Journal: J Phys Chem Lett Year: 2021 Document Type: Article Affiliation country: Acs.jpclett.1c03109