ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Alphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity.Nature communications · 2026Article
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Enhanced efficacy of a next-generation EEEV self-replicating RNA platform for combination cancer immunotherapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Deciphering theVaccines · 2026Article
- Engineering multiple levels of specificity in an RNA viral vector.Nature communications · 2026Article
- RNA-Based Therapeutic Strategies in Multiple Myeloma: From Molecular Targets to Delivery and Clinical Translation.International journal of molecular sciences · 2026Review
- COVID-19 mRNA vaccines: a prospective outlook from technological innovation to clinical practice.Frontiers in immunology · 2026Review
- A Self-Amplifying RNA Lipid Nanoparticle (saRNA-LNP) Vaccine Provides Effective Protection Against Porcine Epidemic Diarrhea.Transboundary and emerging diseases · 2026Article
- Impact of pre-existing anti-replicase immunity on the efficacy of self-amplifying mRNA vaccines.Nature communications · 2025Article
- mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation.Human vaccines & immunotherapeutics · 2025Review
- Divergent Delivery and Expression Kinetics of Lipid and Polymeric Nanoparticles across mRNA Modalities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Laminar fluid ejection device enables high yield and preservation of mRNA and SaRNA LNP formulations.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Self-amplifying RNA (saRNA) vectors are a next-generation RNA technology that extends the expression of heterologous genes. Clinical trials have shown the dose-sparing capacity of saRNA vectors in a vaccine context compared with conventional messenger RNA. However, saRNA vectors have historically been based on a limited number of alphaviruses, and only the Venezuelan equine encephalitis virus-based saRNA vaccines have been used clinically. Here, we designed genotypically distinct alphaviral saRNA vectors and characterized their performance in mammalian cell lines, human skin explants and mice. Five of the 12 vectors had substantial luciferase expression in mice with variable pharmacokinetics, enabling modulation of both the magnitude and duration of protein expression. Additionally, we demonstrated that the alphaviral genotype of the saRNA significantly impacts the immunogenicity of saRNA vaccines, including the humoral and cellular responses in mice. Given the differences in RNA reactogenicity and expression between mice and humans, we assessed the saRNA vectors in human skin explants obtained from patients and observed high transgene expression. saRNA bioluminescence and immunogenicity in different mice strains were highly correlative, while minimal correlation was observed when compared with human explants and mammalian cell lines. This work demonstrates that efficacious saRNA vaccines and therapies can be produced by adapting genetically diverse alphaviruses into vectors.
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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.