ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Corticosteroids and cellulose purification improve, respectively, the in vivo translation and vaccination efficacy of sa-mRNAs.
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 27 papers.
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Who cites it
27 citing papers in PubMed.
- A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Trial
- Influence of the administration route and dose on the expression and antibody responses of a reporter and avian influenza self-amplifying mRNA vaccine in poultry.The veterinary quarterly · 2026Article
- Pulmonary Delivery of Self-Amplifying RNA: Balancing Inflammation and Durable Transgene Expression.ACS nano · 2026Article
- The current landscape of mRNA therapy and the strategies for mRNA purification and dsRNA removal.Journal of biomedical science · 2026Review
- Engineering challenges and translational opportunities in emerging gene delivery platforms.Nature biomedical engineering · 2026Review
- Status and outlook of mRNA therapeutics for viral diseases.EMBO molecular medicine · 2026Review
- Impact of pre-existing anti-replicase immunity on the efficacy of self-amplifying mRNA vaccines.Nature communications · 2025Article
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- mRNA Cancer Vaccines: From Pandemic Paradigm to Personalized Oncology Therapeutics.Cancer innovation · 2025Review
- Article
- 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
- Controlling reactogenicity while preserving immunogenicity from a self-amplifying RNA vaccine by modulating nucleocytoplasmic transport.NPJ vaccines · 2025Article
- Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer.Journal of hematology & oncology · 2025Review
- Repurposing Drugs for Infectious Diseases by Graph Convolutional Network with Sensitivity-Based Graph Reduction.Interdisciplinary sciences, computational life sciences · 2025Article
- A Novel Self-Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Immunogenicity and biodistribution of lipid nanoparticle formulated self-amplifying mRNA vaccines against H5 avian influenza.NPJ vaccines · 2024Article
- Introduction to RNA Vaccines Post COVID-19.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Recent Advances and Innovations in the Preparation and Purification of In Vitro-Transcribed-mRNA-Based Molecules.Pharmaceutics · 2023Review
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10 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Synthetic mRNAs are an appealing platform with multiple biomedical applications ranging from protein replacement therapy to vaccination. In comparison with conventional mRNA, synthetic self-amplifying mRNAs (sa-mRNAs) are gaining interest because of their higher and longer-lasting expression. However, sa-mRNAs also elicit an innate immune response, which may complicate their clinical application. Approaches to reduce the innate immunity of sa-mRNAs have not been studied in detail. Here we investigated, in vivo, the effect of several innate immune inhibitors and a novel cellulose-based mRNA purification approach on the type I interferon (IFN) response and the translation and vaccination efficacy of our formerly developed sa-mRNA vaccine against Zika virus. Among the investigated inhibitors, we found that corticosteroids and especially topical application of clobetasol at the sa-mRNA injection site was the most efficient in suppressing the type I IFN response and increasing the translation of sa-mRNA. However, clobetasol prevented formation of antibodies against sa-mRNA-encoded antigens and should therefore be avoided in a vaccination context. Residual dsRNA by-products of the in vitro transcription reaction are known inducers of immediate type I IFN responses. We additionally demonstrate a drastic reduction of these dsRNA by-products upon cellulose-based purification, reducing the innate immune response and improving sa-mRNA vaccination efficacy.
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