# Sindbis virus self-amplifying replicon is compatible with modified nucleotides mediating expression and vaccine responses in vivo Article · Azizi H, Agbayani G, Renner TM, Simard B, Iqbal U, Dudani R, Jia Y, McCluskie MJ, Akache B - Archive id: doi:10.1016/j.omta.2026.201789 - Published: 2026-06-18 - Venue: Molecular therapy. Advances - DOI: https://doi.org/10.1016/j.omta.2026.201789 - PMID: 42436853 - PMCID: PMC13355167 - Citations: 0 - Source URL: https://doi.org/10.1016/j.omta.2026.201789 - PDF: https://europepmc.org/articles/PMC13355167/pdf - Provenance: europepmc ## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._ Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines) --- Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.