Acid-degradable lipid nanoparticles enhance the delivery of mRNA

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F24%3A10483277" target="_blank" >RIV/00216208:11140/24:10483277 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Zj-52kcNv9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Zj-52kcNv9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41565-024-01765-4" target="_blank" >10.1038/s41565-024-01765-4</a>

Result language

angličtina

Original language name

Acid-degradable lipid nanoparticles enhance the delivery of mRNA

Original language description

Lipid nanoparticle (LNP)-mRNA complexes are transforming medicine. However, the medical applications of LNPs are limited by their low endosomal disruption rates, high toxicity and long tissue persistencetimes. LNPs that rapidly hydrolyse in endosomes (RD-LNPs) could solve the problems limiting LNP-based therapeutics and dramatically expand their applications but have been challenging to synthesize. Here we present an acid-degradable linker termed &apos;azido-acetal&apos; that hydrolyses in endosomes within minutes and enables the production of RD-LNPs. Acid-degradable lipids composed of polyethylene glycol lipids, anionic lipids and cationic lipids were synthesized with the azido-acetal linker and used to generate RD-LNPs, which significantly improved the performance of LNP-mRNA complexes in vitro and in vivo. Collectively, RD-LNPs delivered mRNA more efficiently to the liver, lung, spleen and brains of mice and to haematopoietic stem and progenitor cells in vitro than conventional LNPs. These experiments demonstrate that engineering LNP hydrolysis rates in vivo has great potential for expanding the medical applications of LNPs.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Nature Nanotechnology

ISSN

1748-3387

e-ISSN

1748-3395

Volume of the periodical

19

Issue of the periodical within the volume

11

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

1702-1711

UT code for WoS article

001296611100002

EID of the result in the Scopus database

2-s2.0-85201940309