Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10406 - Analytical chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Angewandte Chemie International Edition
ISSN
1433-7851
e-ISSN
1521-3773
Volume of the periodical
62
Issue of the periodical within the volume
35
Country of publishing house
DE - GERMANY
Number of pages
12
Pages from-to
e20230497
UT code for WoS article
001031289500001
EID of the result in the Scopus database
2-s2.0-85165250820