A self-amplifying RNA vector based on rubella virus for mRNA therapeutics and vaccine applications.

Significant efforts have been made in the burgeoning field of RNA therapies since the COVID-19 pandemic. Self-amplifying RNA (saRNA)-based therapies are considered more promising than conventional messenger RNA due to their lower concentration requirements, long-lasting effects, and self-adjuvanticity. Here, we developed a novel saRNA vector, based on the rubella virus ([RuV], based on the RA27/3 vaccine strain) as an alternative virus-derived replicon that demonstrates effective expression in multiple cell lines and induces immune response. As it is derived from a commonly used vaccine, it potentially offers a better safety profile with reduced risk of adverse events compared with current alphavirus-derived saRNAs. We further optimized this RuV saRNA by screening the capsid region, the nonstructural polyprotein p200 codon, and the 3' untranslated region. This RuV saRNA has great potential to be used as a vaccine vector and in other applications in RNA therapeutics.