Codon harmonization patents as enabling technology for malaria and other diseases

The technique called - codon harmonization - that combines bioinformatics, protein chemistry and genetic engineering to produce novel re-coded gene sequences for expressing recombinant antigens. Codon harmonization addresses several problems inherent to expressing proteins in heterologous hosts such as protein folding and insolubility. Such problems may be due to incorrect modulation of localized translations rates in the heterologous expression host. Codon harmonization engineers recombinant genes with synonymous codons so that codon usage frequencies match those found in the native host for expression in the heterologous host. Particular attention is focused on regions coded by low abundance t-RNA isoacceptor molecules which are predictive of interdomain, nonstructural regions within the protein. WRAIR has applied this technique to several malaria parasite genes including Pf MSP1-42 3D7, Pf MSP1-42 FVO, Pf MSP1-42 CAMP-FUP, Pf LSA1 and PfCelTOS, and has several patent applications related to this technique.