The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines.
COVID-19
N1-methyl-pseudouridine
RNA modification
SARS-CoV-2
lipid nanoparticles
mRNA
pseudouridine
vaccines
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2021
2021
Historique:
received:
04
10
2021
accepted:
22
10
2021
entrez:
22
11
2021
pubmed:
23
11
2021
medline:
23
11
2021
Statut:
epublish
Résumé
The current COVID-19 pandemic is a massive source of global disruption, having led so far to two hundred and fifty million COVID-19 cases and almost five million deaths worldwide. It was recognized in the beginning that only an effective vaccine could lead to a way out of the pandemic, and therefore the race for the COVID-19 vaccine started immediately, boosted by the availability of the viral sequence data. Two novel vaccine platforms, based on mRNA technology, were developed in 2020 by Pfizer-BioNTech and Moderna Therapeutics (comirnaty® and spikevax®, respectively), and were the first ones presenting efficacies higher than 90%. Both consisted of N1-methyl-pseudouridine-modified mRNA encoding the SARS-COVID-19 Spike protein and were delivered with a lipid nanoparticle (LNP) formulation. Because the delivery problem of ribonucleic acids had been known for decades, the success of LNPs was quickly hailed by many as the unsung hero of COVID-19 mRNA vaccines. However, the clinical trial efficacy results of the Curevac mRNA vaccine (CVnCoV) suggested that the delivery system was not the only key to the success. CVnCoV consisted of an unmodified mRNA (encoding the same spike protein as Moderna and Pfizer-BioNTech's mRNA vaccines) and was formulated with the same LNP as Pfizer-BioNTech's vaccine (Acuitas ALC-0315). However, its efficacy was only 48%. This striking difference in efficacy could be attributed to the presence of a critical RNA modification (N1-methyl-pseudouridine) in the Pfizer-BioNTech and Moderna's mRNA vaccines (but not in CVnCoV). Here we highlight the features of N1-methyl-pseudouridine and its contributions to mRNA vaccines.
Identifiants
pubmed: 34805188
doi: 10.3389/fcell.2021.789427
pii: 789427
pmc: PMC8600071
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
789427Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM138387
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA241111
Pays : United States
Informations de copyright
Copyright © 2021 Morais, Adachi and Yu.
Déclaration de conflit d'intérêts
Author PM is Scientific Director (Pseudouridylation Technology) of ProQR Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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