I was listening to the podcast This Week in Virology and a very interesting episode caught my interest. The episode talks about a paper published by Dr. LuisMartÃnez-Sobrido's lab recently that focuses on developing a live-attenuated arenavirus vaccines using codon deoptimization method. Codon deoptimization is something that I've never heard of before but is really effective and meaningful in the field of vaccine development. Their work focuses on one of the arenaviruses - Lassa virus, the cause of Lassa fever, which currently doesn't have FDA approved vaccines. As we all know, many amino acids are coded by more than one codons. However, these codons don't have the same frequencies of being translated because all animals have a codon usage bias. Codon deoptimization is when all the preferred codons are replaced by non preferred codons, thus dramatically reducing the amount of proteins being made. By using codon deoptimization method, they made mutations in one of the nucleoproteins that plays an important part of virus life cycle and largely decreased the viral nucleoprotein translation, ultimately resulting in virus attenuation.
I found this method really impressive and I think it is a promising way to generate more live-attenuated vaccines for other viruses. One concern mentioned by the paper is that codon deoptimization requires computer algorithms to design viral genomes with proper less preferred codons and the use of these new codons might result in different degrees of attenuation. Further improvement can be done in terms of generating consistent degrees of attenuation.
Wenqi Song
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