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Abstract
mRNA protein production was enhanced by up to tenfold in vivo using a new method called ligation-enabled mRNA-oligonucleotide assembly (LEGO).
- A branched mRNA cap effectively initiates translation on both linear and circular mRNAs without the need for internal ribosome entry sites.
- Chemical modifications, including locked nucleic acid (LNA) N-methylguanosine on the cap and additional LNA modifications on the 5' untranslated region, improve the binding of translation initiation factors and RNA stability.
- In a vaccine setting for severe acute respiratory syndrome coronavirus 2, this method resulted in 17-fold and 3.7-fold increases in antibody production after prime and boost doses, respectively.
- The LEGO platform allows for the design of non-traditional RNA structures and topologies that could be useful in both research and therapeutic contexts.
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