Self-amplifying RNA

Not to be confused with small activating RNA.

Self-amplifying RNA (saRNA), also termed self-replicating RNA (srRNA), is a type of mRNA molecule engineered to replicate itself within host cells, enhancing protein expression and boosting the immune response, making it a promising tool for vaccines and other therapeutic applications. As a "next-generation" mRNA, saRNA is designed to achieve greater protein expression with a reduced dose compared to conventional mRNA. Unlike conventional mRNA, which has a short half-life and limited ability to express proteins for an extended time, saRNA can sustain protein expression for longer periods. saRNA are based on positive-sense single-stranded RNA viruses — most commonly alphaviruses such as Venezuelan equine encephalitis virus.

Conventional messenger RNA (mRNA) vaccines only produce a finite amount of protein due to the short mRNA half-life. saRNA extends the kinetics of expression by a second open reading frame (ORF) encoding the protein machinery necessary for its own replication. This self-replication dramatically increases both the amount of RNA and the time of expression. Consequently, the amount of protein produced from the initial dose is increased as compared to conventional mRNA.

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