ArticleScientific reports2019
In vitro evolution of enhanced RNA replicons for immunotherapy.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- "More" Artificial mRNAs: Beyond the Art of Nature.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A Self-Amplifying RNA Lipid Nanoparticle (saRNA-LNP) Vaccine Provides Effective Protection Against Porcine Epidemic Diarrhea.Transboundary and emerging diseases · 2026Article
- Unlocking mRNA-driven CRISPR-Cas9 gene therapy via optimizing mRNA and the delivery vectors.Molecular therapy. Nucleic acids · 2025Review
- Investigation of in vitro delivery conditions for self-amplifying mRNA.Bioprocess and biosystems engineering · 2025Article
- The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity.International journal of molecular sciences · 2025Review
- Article
- Unlock the sustained therapeutic efficacy of mRNA.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.Nature biotechnology · 2025Article
- Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer.Journal of hematology & oncology · 2025Review
- Tumor cell membrane-based vaccines: A potential boost for cancer immunotherapy.Exploration (Beijing, China) · 2024Review
- Neoantigen architectures define immunogenicity and drive immune evasion of tumors with heterogenous neoantigen expression.Journal for immunotherapy of cancer · 2024Article
- A Novel Self-Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Advancements and challenges in mRNA and ribonucleoprotein-based therapies: From delivery systems to clinical applications.Molecular therapy. Nucleic acids · 2024Review
- Review
- Review
- mRNA therapeutics: New vaccination and beyond.Fundamental research · 2023Review
- Mutations in the non-structural protein coding region regulate gene expression from replicon RNAs derived from Venezuelan equine encephalitis virus.Biotechnology letters · 2023Article
- Self-replicating RNA nanoparticle vaccine elicits protective immune responses against SARS-CoV-2.Molecular therapy. Nucleic acids · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Self-replicating (replicon) RNA is a promising new platform for gene therapy, but applications are still limited by short persistence of expression in most cell types and low levels of transgene expression in vivo. To address these shortcomings, we developed an in vitro evolution strategy and identified six mutations in nonstructural proteins (nsPs) of Venezuelan equine encephalitis (VEE) replicon that promoted subgenome expression in cells. Two mutations in nsP2 and nsP3 enhanced transgene expression, while three mutations in nsP3 regulated this expression. Replicons containing the most effective mutation combinations showed enhanced duration and cargo gene expression in vivo. In comparison to wildtype replicon, mutants expressing IL-2 injected into murine B16F10 melanoma showed 5.5-fold increase in intratumoral IL-2 and 2.1-fold increase in infiltrating CD8 T cells, resulting in significantly slowed tumor growth. Thus, these mutant replicons may be useful for improving RNA therapeutics for vaccination, cancer immunotherapy, and gene therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.