ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
A localizing nanocarrier formulation enables multi-target immune responses to multivalent replicating RNA with limited systemic inflammation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Dissolving microneedles for nucleic acid delivery: A systematic search, review, and data synthesis.Acta biomaterialia · 2025Pooled it
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- Next-Generation Nanocarrier Platforms for RNA Vaccines: Advances in Formulation, Stability Engineering, and Translational Manufacturing Challenges.Pharmaceutics · 2026Review
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Immunology of RNA-based vaccines: The critical interplay between inflammation and expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Incorporation of 5-methylcytidine alleviates RIG-I-mediated innate immune responses to a self-amplifying RNA vaccine.Science translational medicine · 2025Article
- A replicating RNA vaccine protects against severe fever with thrombocytopenia syndrome virus infection in mice.NPJ vaccines · 2025Article
- Divergent Delivery and Expression Kinetics of Lipid and Polymeric Nanoparticles across mRNA Modalities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Antigen-dependent interplay of formulation, systemic innate responses, and antibody responses to multi-component replicon RNA vaccination.Molecular therapy. Nucleic acids · 2025Article
- Formulation matters: LION nanoparticles improve RNA vaccine immunogenicity by containing systemic inflammation.Molecular therapy. Nucleic acids · 2025Article
- Article
- The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Promising Vaccine Formulations for Emerging Infectious Diseases.International journal of molecular sciences · 2025Review
- Single-dose replicon RNA Sudan virus vaccine uniformly protects female guinea pigs from disease.Nature communications · 2025Article
- 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
- Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques.iScience · 2025Article
- Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer.Journal of hematology & oncology · 2025Review
- Enhancing RNA vaccine safety through localized delivery strategies.Vaccine insights · 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
16 authors at 2 institutions in 1 country.
Funding
Abstract
RNA vaccines possess significant clinical promise in counteracting human diseases caused by infectious or cancerous threats. Self-amplifying replicon RNA (repRNA) has been thought to offer the potential for enhanced potency and dose sparing. However, repRNA is a potent trigger of innate immune responses in vivo, which can cause reduced transgene expression and dose-limiting reactogenicity, as highlighted by recent clinical trials. Here, we report that multivalent repRNA vaccination, necessitating higher doses of total RNA, could be safely achieved in mice by delivering multiple repRNAs with a localizing cationic nanocarrier formulation (LION). Intramuscular delivery of multivalent repRNA by LION resulted in localized biodistribution accompanied by significantly upregulated local innate immune responses and the induction of antigen-specific adaptive immune responses in the absence of systemic inflammatory responses. In contrast, repRNA delivered by lipid nanoparticles (LNPs) showed generalized biodistribution, a systemic inflammatory state, an increased body weight loss, and failed to induce neutralizing antibody responses in a multivalent composition. These findings suggest that in vivo delivery of repRNA by LION is a platform technology for safe and effective multivalent vaccination through mechanisms distinct from LNP-formulated repRNA vaccines.
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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.