Atomistic Insights into Organization of RNA-Loaded Lipid Nanoparticles

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989100%3A27740%2F23%3A10252578" target="_blank" >RIV/61989100:27740/23:10252578 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15640/23:73620988

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jpcb.2c07671" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jpcb.2c07671</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.2c07671" target="_blank" >10.1021/acs.jpcb.2c07671</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Atomistic Insights into Organization of RNA-Loaded Lipid Nanoparticles

Popis výsledku v původním jazyce

RNA-based therapies have shown promise in a wide range of applications, from cancer therapy, treatment of inherited diseases to vaccination. Encapsulation of RNA into ionizable lipid (IL) containing lipid nanoparticles (LNPs) has enabled its safe and targeted delivery. We present here the simulations of the self-assembly process of pH-sensitive RNA-carrying LNPs and their internal morphology. At low pH, the simulations confirm a lipid core encapsulating RNA in the hexagonal phase. Our all-atom and coarse-grained simulations show that an RNA molecule inside an LNP is protected from interactions with ions by being enveloped in the charged ILs. At neutral pH, representing the environment after LNP administration into human tissues, LNPs expelled most of the encapsulated RNA and water and formed separate bulk IL-rich and ordered the helper-lipid-rich phase. Helper lipids arranged themselves to be in contact with RNA or water. The presented models provide atomistic understanding of the LNP structure and open a way to investigate them in silico, varying the LNP composition or interacting with other biostructures aiming at increasing the efficiency of RNA-based medicine.

Název v anglickém jazyce

Atomistic Insights into Organization of RNA-Loaded Lipid Nanoparticles

Popis výsledku anglicky

RNA-based therapies have shown promise in a wide range of applications, from cancer therapy, treatment of inherited diseases to vaccination. Encapsulation of RNA into ionizable lipid (IL) containing lipid nanoparticles (LNPs) has enabled its safe and targeted delivery. We present here the simulations of the self-assembly process of pH-sensitive RNA-carrying LNPs and their internal morphology. At low pH, the simulations confirm a lipid core encapsulating RNA in the hexagonal phase. Our all-atom and coarse-grained simulations show that an RNA molecule inside an LNP is protected from interactions with ions by being enveloped in the charged ILs. At neutral pH, representing the environment after LNP administration into human tissues, LNPs expelled most of the encapsulated RNA and water and formed separate bulk IL-rich and ordered the helper-lipid-rich phase. Helper lipids arranged themselves to be in contact with RNA or water. The presented models provide atomistic understanding of the LNP structure and open a way to investigate them in silico, varying the LNP composition or interacting with other biostructures aiming at increasing the efficiency of RNA-based medicine.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

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

Návaznosti

—

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

1520-5207

Svazek periodika

127

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

1158-1166

Kód UT WoS článku

000911908500001

EID výsledku v databázi Scopus

2-s2.0-85146043204