ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Innate Inhibiting Proteins Enhance Expression and Immunogenicity of Self-Amplifying RNA.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 94 citations in OpenAlex.
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity.Nature communications · 2026Article
- Enhancing Lipid Nanoparticle-Mediated Circular RNA and mRNA Expression in the Placenta through Inhibition of IFNAR-JAK-STAT Signaling.Nano letters · 2026Article
- A novel self-amplified RNA vaccine co-expressing NA and HA1 delivered by Salmonella confers potent protection against H9N2 influenza in chickens.Poultry science · 2026Article
- A self-amplifying RNA vector based on rubella virus for mRNA therapeutics and vaccine applications.Molecular therapy. Nucleic acids · 2026Article
- Emerging Non-Conventional Approaches in mRNA-LNP Formulation for Therapeutic Applications.Pharmaceutics · 2026Review
- Systems vaccinology analysis of saRNA immunization identifies an acute innate immune signature correlated with adaptive immunity.Molecular therapy. Advances · 2026Article
- Review
- A second-generation, self-amplifying COVID-19 Vaccine: World's first approval and distribution in the Japanese market with vaccine hesitancy.Human vaccines & immunotherapeutics · 2025Review
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- Investigation of in vitro delivery conditions for self-amplifying mRNA.Bioprocess and biosystems engineering · 2025Article
- Optimization of In Vitro Transcription by Design of Experiment to Achieve High Self-Amplifying RNA Integrity.Vaccines · 2025Article
- The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity.International journal of molecular sciences · 2025Review
- Article
- Eliciting antitumor immunity via therapeutic cancer vaccines.Cellular & molecular immunology · 2025Review
- Unlock the sustained therapeutic efficacy of mRNA.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Co-expression of HSV-1 ICP34.5 enhances the expression of gene delivered by self-amplifying RNA and mitigates its immunogenicity.FEBS open bio · 2025Article
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.Nature biotechnology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Self-amplifying RNA (saRNA) is a cutting-edge platform for both nucleic acid vaccines and therapeutics. saRNA is self-adjuvanting, as it activates types I and III interferon (IFN), which enhances the immunogenicity of RNA vaccines but can also lead to inhibition of translation. In this study, we screened a library of saRNA constructs with cis-encoded innate inhibiting proteins (IIPs) and determined the effect on protein expression and immunogenicity. We observed that the PIV-5 V and Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a proteins enhance protein expression 100- to 500-fold in vitro in IFN-competent HeLa and MRC5 cells. We found that the MERS-CoV ORF4a protein partially abates dose nonlinearity in vivo, and that ruxolitinib, a potent Janus kinase (JAK)/signal transducer and activator of transcription (STAT) inhibitor, but not the IIPs, enhances protein expression of saRNA in vivo. Both the PIV-5 V and MERS-CoV ORF4a proteins were found to enhance the percentage of resident cells in human skin explants expressing saRNA and completely rescued dose nonlinearity of saRNA. Finally, we observed that the MERS-CoV ORF4a increased the rabies virus (RABV)-specific immunoglobulin G (IgG) titer and neutralization half-maximal inhibitory concentration (IC
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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.