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143. Is there evidence that demonstrates that three potentially ineffective stop codons are any better than one. A leaky bucket is a leaky bucket is it not? Can data please be provided to prove that Methylpseudouridine is just as effective as uridine in stopping codon read through?

Question Number: 271
PDR Number: SQ22-000642
Date Submitted: 21/11/2022
Department or Body: Department of Health

Yes – methylpseudouridine is as effective as uridine in stopping codon read through. It is reported in the literature that methylpseudouridine enhances RNA stability and decreases anti-RNA immune response. It is also reported that fully modified RNA’s (U substituted with N1-methylpseudouridine) are likely to have high coding fidelity as they are known to prevent wobble-pairing with other nucleotides. The placement of two and three contiguous codons in the Pfizer and Moderna vaccines, respectively, ensure no-read through of modified stop codons occurs as a single methylpseudouridine stop codon would allow, to some extent, read-through. A copy of the report is available at: www.frontiersin.org/articles/10.3389/fcell.2021.789427/full.

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