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N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products

ABSTRACT: N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products

PROVIDER: PRJNA773947 | ENA |

REPOSITORIES: ENA

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N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products

Project description:The COVID mRNA vaccines utilize the modified nucleobase N1-methylpseudouridine, in place of canonical uridine, to improve immunogenicity and protein yield. However, relatively few studies have investigated the effect of modified nucleobases on the fidelity of protein translation. Given the interest in the COVID mRNA vaccines, we sought to investigate how N1-methylpseudouridine (and the related modification pseudouridine) is read by ribosomes.

2022-08-18 | PXD029291 | Pride

N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products

Project description:Given the interest in the COVID mRNA vaccines, we sought to investigate how the RNA modification N1-methylpseudouridine (and its related modification, pseudouridine) is read by ribosomes and reverse transcriptases. By looking at reverse transcriptase data, we can gain information on how the modification affects duplex stability, which may have important consequences for the tRNA-mRNA interactions found in the ribosome.

2021-10-25 | GSE186464 | GEO

N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products.

Project description:Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the technology is the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) to decrease immunogenicity of the RNA. However, relatively few studies have addressed the effects of modified nucleotides on the decoding process. Here, we investigate the effect of m1Ψ and the related modification pseudouridine (Ψ) on translation. In a reconstituted system, we find that m1Ψ does not significantly alter decoding accuracy. More importantly, we do not detect an increase in miscoded peptides when mRNA containing m1Ψ is translated in cell culture, compared with unmodified mRNA. We also find that m1Ψ does not stabilize mismatched RNA-duplex formation and only marginally promotes errors during reverse transcription. Overall, our results suggest that m1Ψ does not significantly impact translational fidelity, a welcome sign for future RNA therapeutics.

| S-EPMC9376333 | biostudies-literature

The Effect of Calcium on Activity, Immunogenicity and Efficacy of a Recombinant N1/N2 Neuraminidase Vaccine

Project description:Despite the importance of immunity against neuraminidase (NA), NA content and immunogenicity is neglected in current influenza vaccines. To address this, a novel recombinant N1/N2 NA vaccine (NAV) was developed. Stability assays were used to determine optimal temperature and buffer conditions for vaccine storage. The effect of calcium-related enhancement of NA stability and activity on N1 and N2 immunogenicity and efficacy against viral challenge was assessed. Differences in activity between N1 and N2 and calcium-related activity enhancement did not translate into differences in immunogenicity or efficacy. NAV vaccinated mice showed robust antibody titers against N1 and N2, decreased viral titers, and decreased antiviral and inflammatory responses by transcriptomic analysis.

2021-03-30 | GSE160010 | GEO

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