ArticleProceedings of the National Academy of Sciences of the United States of America2023
Comb-structured mRNA vaccine tethered with short double-stranded RNA adjuvants maximizes cellular immunity for cancer treatment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- Recent advances in lipid nanoparticles for cancer vaccine delivery: Challenges and future perspectives.International journal of pharmaceutics: X · 2026Review
- Influenza mRNA vaccine with engineered panhandle-forming UTRs provides potent, dose-sparing protection against seasonal influenza viruses.NPJ vaccines · 2026Article
- Engineering polymeric RNA scaffolds as programmable combinatorial innate immune agonists.Nucleic acids research · 2026Article
- Fc-free single-chain antibody mRNA therapy for airway infection of multidrug-resistant Pseudomonas aeruginosa.Nature communications · 2026Article
- Cytokine mRNA-based therapy alleviates dendritic cell and T cell paucity to eliminate aggressive pancreatic cancer in preclinical mouse models.EBioMedicine · 2026Article
- Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.Biomaterials translational · 2026Article
- mRNA vaccines: immunogenicity and quality characteristics.Journal of nanobiotechnology · 2025Review
- Advances in nanocarrier-mediated cancer therapy: Progress in immunotherapy, chemotherapy, and radiotherapy.Chinese medical journal · 2025Review
- Eliciting antitumor immunity via therapeutic cancer vaccines.Cellular & molecular immunology · 2025Review
- Cancer vaccines: current status and future directions.Journal of hematology & oncology · 2025Review
- 5' terminal nucleotide determines the immunogenicity of IVT RNAs.Nucleic acids research · 2025Article
- In Vivo Interactions of Nucleic Acid Nanostructures With Cells.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Nucleic acid vaccines: innovations, efficacy, and applications in at-risk populations.Frontiers in immunology · 2025Review
- Recent progress in mRNA cancer vaccines.Human vaccines & immunotherapeutics · 2024Review
- Advances in therapeutic cancer vaccines: Harnessing immune adjuvants for enhanced efficacy and future perspectives.Computational and structural biotechnology journal · 2024Review
- A nucleoside-modified mRNA vaccine forming rabies virus-like particle elicits strong cellular and humoral immune responses against rabies virus infection in mice.Emerging microbes & infections · 2024Article
- IL-7 promotes mRNA vaccine-induced long-term immunity.Journal of nanobiotechnology · 2024Article
- mRNA vaccines in tumor targeted therapy: mechanism, clinical application, and development trends.Biomarker research · 2024Review
- Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.Journal of nanobiotechnology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrating antigen-encoding mRNA (Messenger RNA) and immunostimulatory adjuvant into a single formulation is a promising approach to potentiating the efficacy of mRNA vaccines. Here, we developed a scheme based on RNA engineering to integrate adjuvancy directly into antigen-encoding mRNA strands without hampering the ability to express antigen proteins. Short double-stranded RNA (dsRNA) was designed to target retinoic acid-inducible gene-I (RIG-I), an innate immune receptor, for effective cancer vaccination and then tethered onto the mRNA strand via hybridization. Tuning the dsRNA structure and microenvironment by changing its length and sequence enabled the determination of the structure of dsRNA-tethered mRNA efficiently stimulating RIG-I. Eventually, the formulation loaded with dsRNA-tethered mRNA of the optimal structure effectively activated mouse and human dendritic cells and drove them to secrete a broad spectrum of proinflammatory cytokines without increasing the secretion of anti-inflammatory cytokines. Notably, the immunostimulating intensity was tunable by modulating the number of dsRNA along the mRNA strand, which prevents excessive immunostimulation. Versatility in the applicable formulation is a practical advantage of the dsRNA-tethered mRNA. Its formulation with three existing systems, i.e., anionic lipoplex, ionizable lipid-based lipid nanoparticles, and polyplex micelles, induced appreciable cellular immunity in the mice model. Of particular interest, dsRNA-tethered mRNA encoding ovalbumin (OVA) formulated in anionic lipoplex used in clinical trials exerted a significant therapeutic effect in the mouse lymphoma (E.G7-OVA) model. In conclusion, the system developed here provides a simple and robust platform to supply the desired intensity of immunostimulation in various formulations of mRNA cancer vaccines.
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