Pseudouridine-modified in vitro-transcribed mRNA Caused+1 Ribosomal Frameshifting During Protein Translation
Pseudouridine(Ψ)-modified in vitro-transcribed mRNA(Ψ-IVT-mRNA)is used in two li-censed SARS-CoV-2 mRNA vaccines in response to the COVID-19 pandemic worldwide.Recently the Ψ-IVT-mRNA has been demonstrated to cause ribosome stalling and lead to+1 ribosomal frameshifting both in vitro and in vivo,resulting in aberrant protein products.The aberrant proteins may have the potential to induce off-target T-cell or antibody responses and other unintended side effects in people vaccinated with SARS-CoV-2 mRNA vaccines.The finding highlights a key aspect of developing mRNA-based vaccines/therapeutics with improved outcomes.
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