LinearDesign is out! (from the authors of LinearFold and LinearPartition)

It turns out we can computationally design the most stable mRNA sequence for any given protein. For the spike protein of SARS-CoV-2 (which Moderna uses for its mRNA-1273 vaccine), LinearDesign exact mode takes ~1.6 hours (achieving free energy -2477.7 kcal/mol), and LinearDesign beam size b=1000 takes ~20 minutes with ~0.6% free energy loss.

By comparison, the wild type (in the virus) is only -1075.4 kcal/mol, and the best random sequence (among 5,000 sequences taken randomly but using codons proportional to human codon usage) is -1220.3 kcal/mol, suggesting that the designed mRNA sequence is far more stable.



It would be interesting to compare the WT virus mRNA to the LinearDesign stabilized mRNA to see what mutations were used and where they were applied. We could do a lot with that information. 
Congratulations on this achievement!  

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LinearDesign-3 was chosen for the first round of Spike designs being tested, which is Round 3 of the OpenVaccine Project.

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Thanks again Omei!

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