Algorithm for optimized mRNA design improves stability and immunogenicity

Abstract Messenger RNA (mRNA) vaccines are being used to combat the spread of COVID-19 (refs. 1–3 ), but they still exhibit critical limitations caused by mRNA instability and degradation, which are major obstacles for the storage, distribution and efficacy of the vaccine products 4 . Increasing secondary structure lengthens mRNA half-life, which, together with optimal codons, improves protein expression 5 . Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage. However, owing to synonymous codons, the mRNA design space is prohibitively large—for example, there are around 2.4 × 10 632 candidate mRNA sequences for the SARS-CoV-2 spike protein. This poses…

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