Role of Ionizable Lipids in SARS-CoV-2 Vaccines As Revealed by Molecular Dynamics Simulations: From Membrane Structure to Interaction with mRNA Fragments

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989100%3A27740%2F21%3A10249005" target="_blank" >RIV/61989100:27740/21:10249005 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15640/21:73610651

Výsledek na webu

<a href="https://doi.org/10.1021/acs.jpclett.1c03109" target="_blank" >https://doi.org/10.1021/acs.jpclett.1c03109</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpclett.1c03109" target="_blank" >10.1021/acs.jpclett.1c03109</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of Ionizable Lipids in SARS-CoV-2 Vaccines As Revealed by Molecular Dynamics Simulations: From Membrane Structure to Interaction with mRNA Fragments

Popis výsledku v původním jazyce

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. (C)

Název v anglickém jazyce

Role of Ionizable Lipids in SARS-CoV-2 Vaccines As Revealed by Molecular Dynamics Simulations: From Membrane Structure to Interaction with mRNA Fragments

Popis výsledku anglicky

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. (C)

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

Projekt

<a href="/cs/project/EF16_019%2F0000754" target="_blank" >EF16_019/0000754: Nanotechnologie pro budoucnost</a><br>

Návaznosti

—

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physical Chemistry Letters

ISSN

1948-7185

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

45

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

11199-11205

Kód UT WoS článku

000744193000003

EID výsledku v databázi Scopus

2-s2.0-85119592560