Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2FCZ______%3A_____%2F23%3AN0000080" target="_blank" >RIV/CZ______:_____/23:N0000080 - isvavai.cz</a>

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/10.1002/anie.202304977" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/anie.202304977</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.202304977" target="_blank" >10.1002/anie.202304977</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Angewandte Chemie International Edition

ISSN

1433-7851

e-ISSN

1521-3773

Svazek periodika

62

Číslo periodika v rámci svazku

35

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

e20230497

Kód UT WoS článku

001031289500001

EID výsledku v databázi Scopus

2-s2.0-85165250820