Key result
Rational genetic design of viral genomes, including altering dinucleotide frequencies, deoptimizing codons, and decreasing mutational robustness, offers a promising strategy to develop safe live-attenuated vaccines.
Why the study?
Rational genetic design strategies altering viral genomic compositional features are emerging to replace empirical approaches for developing live-attenuated vaccines.
Rational genetic design of viral genomes through codon rewiring and altering mutational robustness offers a promising approach to create safe and stable live-attenuated vaccines.
May guide preclinical vaccine research; leaves open clinical translation and regulatory pathways.
Live-attenuated vaccines have been historically used to successfully prevent numerous diseases caused by a broad variety of RNA viruses due to their ability to elicit strong and perdurable immune-protective responses. In recent years, various strategies have been explored to achieve viral attenuation by rational genetic design rather than using classic and empirical approaches, based on successive passages in cell culture. A deeper understanding of evolutionary implications of distinct viral genomic compositional aspects, as well as substantial advances in synthetic biology technologies, have provided a framework to achieve new viral attenuation strategies. Herein, we will discuss different approaches that are currently applied to modify compositional features of viruses in order to develop novel live-attenuated vaccines.
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Pereira-Gómez et al. (2021) conducted a review in Viral diseases. Rational genetic design of viral genomes (codon deoptimization, dinucleotide alteration, mutational robustness decrease) vs. Traditional empirical attenuation was evaluated. Rational genetic design of viral genomes, including altering dinucleotide frequencies, deoptimizing codons, and decreasing mutational robustness, offers a promising strategy to develop safe live-attenuated vaccines.
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