This technique reduces (and might prevent) the induction of innate immunity against the mRNA. It uses exchange of synonymous codons throughout the coding sequence following a particular exchange table. The goal of the procedure is to break-up subsequences that are known to have a high affinity for the TLR-7 and -8. As a result, TLR-7 and -8 do not activate the IFN-I pathway via MyD88, so protein expression is not reduced and pro-inflammatory cytokines are not released.
The difficulty with this method is that it must work within the context of the evolutionary optimized sequence, as mutations on the protein level are usually not desirable, and for certain codons there is limited or no alternative. Furthermore, by performing codon exchange the secondary structure of the mRNA, codon optimality, and potentially even protein folding dictated by the translational speed changes. Therefore, RIBOPRO has developed an algorithm that uses state-of-the-art models of each parameter and performs millions of in silico folding and codon-use analyses to arrive at the proposed optimized sequence. In the ideal situation, multiple variants of a construct are tested side-by-side and the results are used for informed evolution of the construct.
The benefit of using this method, over the only alternative; the use of chemically modified nucleotides, is 2-fold:
a. it produces similarly de-immunized mRNA, but does not have the ribosomal misinterpretation of the chemically modified nucleotides, which leads to read-through and possibly auto-immunity-inducing misincorporated amino acids. This seems to be not a great issue for vaccination, but for (repeated) therapeutic use, this is a major cause for concern. The use of only canonical nucleotides generates a more safe and unique (patentable by you) sequence that produces between 5 and 40x more protein than its wild-type counterpart.
b. clarity and cooperation on the IP-situation; you only have to deal with RIBOPRO, who has a vested interest in your success and market entry.