Sindbis virus self-amplifying replicon is compatible with modified nucleotides mediating expression and vaccine responses <i>in vivo</i>

Abstract

The advent of effective formulations based on RNA encapsulated within lipid nanoparticles has led to the evaluation of this technology for its ability to treat and prevent a wide range of diseases. Expansion of the RNA-based tool kit available to vaccine and drug developers will accelerate this development and hopefully produce more robust and cost-effective therapies. With its more sustained expression profile, self-amplifying RNA offers many advantages to standard messenger RNA, allowing for the administration of lower RNA doses in vivo and potentially reducing dosing frequency for indications where long-term expression of a protein is required. We generated self-amplifying RNA containing the viral replicon from Sindbis virus, which demonstrated robust protein expression in vitro and in vivo . In addition, it showed increased compatibility with a number of modified nucleotides when compared to an equivalent RNA containing the replicon from Venezuelan equine encephalitis virus. These Sindbis-based self-amplifying RNAs containing modified nucleotides have the potential to be used in a variety of experimental and therapeutic applications.

Abstract of "Sindbis virus self-amplifying replicon is compatible with modified nucleotides mediating expression and vaccine responses <i>in vivo</i>" by Azizi H, Agbayani G, Renner TM et al., https://doi.org/10.1016/j.omta.2026.201789, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.