ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
mRNA-LNPs induce immune activation and cytokine release in human whole blood assays across diverse health conditions.
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 29 papers.
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Who cites it
29 citing papers in PubMed.
- Engineering tolerogenic mRNA-LNPs for allergen-specific immune reprogramming in pollen allergy.Materials today. Bio · 2026Article
- New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.Nature nanotechnology · 2026Article
- Antiviral efficacy of LNP-delivered IFN-α14-ApoAI mRNA for chronic hepatitis B.Journal of virus eradication · 2026Article
- Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.Precision clinical medicine · 2026Review
- An inherent T cell-activating mRNA delivery carrier for in vivo CAR T generation.Nature materials · 2026Article
- Pulmonary Delivery of Self-Amplifying RNA: Balancing Inflammation and Durable Transgene Expression.ACS nano · 2026Article
- Precision engineering of macrophage reprogramming with RNA interference-loaded lipid nanoparticles: a game-changer in cancer immunotherapy.Drug delivery and translational research · 2026Review
- Immune protection in chickens via lipid nanoparticle-encapsulated VP2 DNA vaccine against very virulent infectious bursal disease virus.Poultry science · 2026Article
- mRNA Vaccines for Influenza: Hope for a Universal Vaccine?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation.Biomedicines · 2026Review
- Poly(I:C) Lipoamino Bundle LNPs Induce Tumor Cytotoxicity and Immune Activation with Enhanced Efficacy by Survivin Silencing.International journal of molecular sciences · 2026Article
- Inhaled nucleic acid delivery systems for the treatment of pulmonary interstitial diseases: Challenges and opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Breathing lung-on-chip: a versatile tool for assessing respiratory toxicity across multiple therapeutic modalities.Archives of toxicology · 2026Article
- Single intramuscular injection of self-amplifying RNA ofScience (New York, N.Y.) · 2026Article
- Lipid nanoparticle GM-CSF replacement for autoimmune pulmonary alveolar proteinosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The evolution of lipid nanoparticles: Paving the way for next-generation nucleic acid medicines.Asian journal of pharmaceutical sciences · 2026Review
- Lipid Nanoparticle Development in Practice: Challenges and Collective Insights.Pharmaceutical research · 2026Review
- Lung-targeted RNA delivery systems: strategies and therapeutic applications.Journal of nanobiotechnology · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA medicines have become a promising platform for therapeutic use in recent years. Understanding the immunomodulatory effects of novel mRNA-lipid nanoparticles (LNPs) is crucial for future therapeutic development. An in vitro whole blood assay was developed to assess the impact of mRNA-LNPs on immune cell function, cytokine release, and complement activation. mRNA-LNPs significantly increased CD69 expression on T cells and natural killer cells, and CD80/CD86 on myeloid subsets, in a dose-dependent fashion. Furthermore, mRNA-LNPs elicited a robust release of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, monocyte chemoattractant protein-1, IL-6, and IP-10, indicating a potent immune response. Notably, mRNA-LNPs stimulate early cytokine production prior to triggering immune cell activation, suggesting a temporal and biological relationship. Moreover, mRNA-LNPs induce complement activation via the alternative pathway, as evidenced by increased serum sC5b-9, C3a, and Bb, which can amplify the inflammatory response and potentially impact safety. In vitro effects of mRNA-LNPs in whole blood of healthy human donors were compared with those from disease cohorts including systemic lupus erythematosus, type 2 diabetes mellitus, and cancer donors. The differences in mRNA-LNP effects on samples from healthy and diseased populations may impact therapeutic efficacy or toxicity, indicating a need for tailoring LNPs for specific target populations.
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