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Modified messenger-RNA components alter the encoded protein

Modified components of messenger RNA can cause the protein-production machinery to stall during the process of translation. This might change the protein being made, a finding with implications for vaccines or therapies.
  1. Nicholas J. Tursi

    1. Nicholas J. Tursi is at the Vaccine and Immunotherapy Center, The Wistar Institute, and at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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  2. David B. Weiner

    1. David B. Weiner is at the Vaccine and Immunotherapy Center, The Wistar Institute, and at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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Advances made in messenger RNA technology led to two mRNA vaccines that target SARS-CoV-2 having an important role in the response to the COVID-19 pandemic. Rather than making the mRNA using cells, these vaccines use mRNA that is made in vitro in the laboratory and is known as in vitro transcribed (IVT) mRNA. Understanding the details of how IVT mRNA encodes protein during the process of translation (protein production mediated by the machinery of ribosomes and transfer RNAs) might contribute to future applications of this type of technology. Writing in Nature, Mulroney et al.1 reveal that the ribosome can stall at ‘slippery’ sequences along modified versions of mRNA (ones that include some nucleoside components that have been chemically modified); this might result in aberrant protein products. In the context of such nucleoside-modified mRNA vaccines and other non-vaccine therapeutic RNAs, this might lead to unintended consequences.

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Nature 625, 37-38 (2024)

doi: https://doi.org/10.1038/d41586-023-03787-9

References

  1. Mulroney, T. E. et al. Nature 625, 189–194 (2024).

    Article  Google Scholar 

  2. Karikó, K., Buckstein, M., Ni, H. & Weissman, D. Immunity 23, 165–175 (2005).

    Article  PubMed  Google Scholar 

  3. Karikó, K. et al. Mol. Ther. 16, 1833–1840 (2008).

    Article  PubMed  Google Scholar 

  4. Atkins, J. F., Loughran, G., Bhatt, P. R., Firth, A. E. & Baranov, P. V. Nucleic Acids Res. 44, 7007–1078 (2016).

    PubMed  Google Scholar 

  5. Champagne, J., Mordente, K., Nagel, R. & Agami, R. Trends Genet. 38, 1123–1133 (2022).

    Article  PubMed  Google Scholar 

  6. Ketteler, R. Front. Genet. 3, 242 (2012).

    Article  PubMed  Google Scholar 

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Competing Interests

D.B.W. notes several possible competing interests, which are managed by the Wistar General Council Office COI committee. These include consulting, BOD service, speaking, that can include in stock or monetary renumeration, and specific SRAs. Inovio Pharmaceuticals (BOD, consultant and SRA); AstraZeneca (speaker/consultant); Advaccine (consultant); Pfizer (speaker/advisory service); Geneos (consultant & SRA); Flagship (consultant); Sumitomo Pharma (consultant); plus possibly others that are managed by Wistar COI Committee. D.B.W. is a member of the International Society for Vaccines, AAI, ASGCT, AAAS, among other scientific societies. He also serves on NIH and NCI study sections and similar activities for other agencies.

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