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bioRxiv · 10.1101/2021.08.30.458298

Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails

Liu, Y.·Nie, H.·Sun, R.·Wang, J.·Lu, F.
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Abstract

In vitro transcribed (IVT) mRNA represents a new class of drug in both therapeutics and vaccines. Improving the translation efficiency of IVT mRNA remains a core challenge for mRNA-based applications. Here, using IVT mRNAs with poly(A) tails containing non-A residues which were recently revealed to be widespread in RNA poly(A) tails1,2, we unexpectedly find that non-A residues can effectively promote the mRNA translation. To further support our finding, we provide evidence that non-A residues associated with enhanced mRNA translation efficiency transcriptome-wide in mouse and human cells. Together, our study provides a novel approach to enhance mRNA translation efficiency by inclusion of non-A residues in the mRNA poly(A) tails, holding great potential to promote mRNA-based therapeutics and vaccines.

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Liu, Y., Nie, H., Sun, R., Wang, J., Lu, F.. 2021-08-31. Enhancement of synthetic mRNA translation efficiency through engineered poly(A) tails. https://doi.org/10.1101/2021.08.30.458298

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