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mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability

2021· review· en· 1,476 citations· W3148255637 on OpenAlex· 10.1016/j.ijpharm.2021.120586

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A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

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Opus teacher head0.080
GPT teacher head0.419
Teacher spread
0.340 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

A drawback of the current mRNA-lipid nanoparticle (LNP) COVID-19 vaccines is that they have to be stored at (ultra)low temperatures. Understanding the root cause of the instability of these vaccines may help to rationally improve mRNA-LNP product stability and thereby ease the temperature conditions for storage. In this review we discuss proposed structures of mRNA-LNPs, factors that impact mRNA-LNP stability and strategies to optimize mRNA-LNP product stability. Analysis of mRNA-LNP structures reveals that mRNA, the ionizable cationic lipid and water are present in the LNP core. The neutral helper lipids are mainly positioned in the outer, encapsulating, wall. mRNA hydrolysis is the determining factor for mRNA-LNP instability. It is currently unclear how water in the LNP core interacts with the mRNA and to what extent the degradation prone sites of mRNA are protected through a coat of ionizable cationic lipids. To improve the stability of mRNA-LNP vaccines, optimization of the mRNA nucleotide composition should be prioritized. Secondly, a better understanding of the milieu the mRNA is exposed to in the core of LNPs may help to rationalize adjustments to the LNP structure to preserve mRNA integrity. Moreover, drying techniques, such as lyophilization, are promising options still to be explored.

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The record

Venue
International Journal of Pharmaceutics
Topic
RNA Interference and Gene Delivery
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
NanoMedicines Innovation NetworkBC Innovation CouncilUniversity of British Columbia
Funders
Universiteit Leiden
Keywords
Messenger RNAChemistryBiochemistryGene
Has abstract in OpenAlex
yes