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

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...

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Autores principales: Schoenmaker, Linde, Witzigmann, Dominik, Kulkarni, Jayesh A., Verbeke, Rein, Kersten, Gideon, Jiskoot, Wim, Crommelin, Daan J.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier B.V. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032477/
https://www.ncbi.nlm.nih.gov/pubmed/33839230
http://dx.doi.org/10.1016/j.ijpharm.2021.120586
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author Schoenmaker, Linde
Witzigmann, Dominik
Kulkarni, Jayesh A.
Verbeke, Rein
Kersten, Gideon
Jiskoot, Wim
Crommelin, Daan J.A.
author_facet Schoenmaker, Linde
Witzigmann, Dominik
Kulkarni, Jayesh A.
Verbeke, Rein
Kersten, Gideon
Jiskoot, Wim
Crommelin, Daan J.A.
author_sort Schoenmaker, Linde
collection PubMed
description 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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spelling pubmed-80324772021-04-09 mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability Schoenmaker, Linde Witzigmann, Dominik Kulkarni, Jayesh A. Verbeke, Rein Kersten, Gideon Jiskoot, Wim Crommelin, Daan J.A. Int J Pharm Review 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. The Author(s). Published by Elsevier B.V. 2021-05-15 2021-04-09 /pmc/articles/PMC8032477/ /pubmed/33839230 http://dx.doi.org/10.1016/j.ijpharm.2021.120586 Text en © 2021 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Review
Schoenmaker, Linde
Witzigmann, Dominik
Kulkarni, Jayesh A.
Verbeke, Rein
Kersten, Gideon
Jiskoot, Wim
Crommelin, Daan J.A.
mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
title mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
title_full mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
title_fullStr mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
title_full_unstemmed mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
title_short mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability
title_sort mrna-lipid nanoparticle covid-19 vaccines: structure and stability
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032477/
https://www.ncbi.nlm.nih.gov/pubmed/33839230
http://dx.doi.org/10.1016/j.ijpharm.2021.120586
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