biostudies-literatureUnknown10von der Haar T<i>In vitro</i> transcribed, modified messenger RNAs (IVTmRNAs) have been used to vaccinate billions of individuals against the SARS-CoV-2 virus, and are currently being developed for many additional therapeutic applications. IVTmRNAs must be translated into proteins with therapeutic activity by the same cellular machinery that also translates native endogenous transcripts. However, different genesis pathways and routes of entry into target cells as well as the presence of modified nucleotides mean that the way in which IVTmRNAs engage with the translational machinery, and the efficiency with which they are being translated, differs from native mRNAs. This review summarises our current knowledge of commonalities and differences in translation between IVTmRNAs and cellular mRNAs, which is kFrontiers in molecular biosciences1128067https://www.ebi.ac.uk/biostudies/studies/S-EPMC9943971biostudies-literatureTranslation of <i>in vitro</i>-transcribed RNA therapeutics.PMC9943971Hedayioglu FRust MLilley KSThaventhiran JEKurusamy SSmales CMvon der Haar TWillis AEMulroney TEfalseTranslation of <i>in vitro</i>-transcribed RNA therapeutics.<i>In vitro</i> transcribed, modified messenger RNAs (IVTmRNAs) have been used to vaccinate billions of individuals against the SARS-CoV-2 virus, and are currently being developed for many additional therapeutic applications. IVTmRNAs must be translated into proteins with therapeutic activity by the same cellular machinery that also translates native endogenous transcripts. However, different genesis pathways and routes of entry into target cells as well as the presence of modified nucleotides mean that the way in which IVTmRNAs engage with the translational machinery, and the efficiency with which they are being translated, differs from native mRNAs. This review summarises our current knowledge of commonalities and differences in translation between IVTmRNAs and cellular mRNAs, which is k2023-01-01T00:00:00Z20232025-04-04T14:17:42.898Z2025-02-19T02:23:49.959ZS-EPMC99439713684554010.3389/fmolb.2023.1128067