ArticleNature biomedical engineering2024
Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d.
Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed.
- Human T cell engineering via serial delivery of mRNA encapsulated within lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026Review
- Ionizable Lipid-Dependent Optimization of Steroid Lipid Nanoparticles With Tunable Immunomodulatory Properties.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026Article
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- mRNA lipid nanoparticle vaccines: current status, challenges and future prospects.Molecular biomedicine · 2026Review
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- Ligand-Mediated Reprogramming Redirects Liver-Tropic Ionizable Lipid Nanoparticles for Lung-Selective mRNA Delivery.Angewandte Chemie (International ed. in English) · 2026Article
- Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.Nature nanotechnology · 2026Article
- Low reactogenicity and high tumour antigen expression from mRNA-LNPs with membrane-destabilizing zwitterionic lipids.Nature biomedical engineering · 2026Article
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
- Delivering Degradation: Nanomedicine and Programmable Proximity Platforms for Targeted Protein Degradation.Pharmaceutics · 2026Review
- Critical chemistry manufacturing and controls considerations for mRNA lipid nanoparticle translation.Discover nano · 2026Review
- Defining Composition-Cytokine Relationships Enables the Design of Lipid Nanoparticles with Programmed Immunogenicity.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Two Classes of Protein Therapeutics: Why Dose-Response Architecture Defines the Boundary of mRNA Medicines.Pharmaceutics · 2026Review
- Silk-Based Protein Corona Enhances mRNA-LNP Vaccine Efficacy and Prevents Tumor Relapse.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Precision engineering of macrophage reprogramming with RNA interference-loaded lipid nanoparticles: a game-changer in cancer immunotherapy.Drug delivery and translational research · 2026Review
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Lipid nanoparticles (LNPs) are the most clinically advanced delivery vehicle for RNA therapeutics, partly because of established lipid structure-activity relationships focused on formulation potency. Yet such knowledge has not extended to LNP immunogenicity. Here we show that the innate and adaptive immune responses elicited by LNPs are linked to their ionizable lipid chemistry. Specifically, we show that the amine headgroups in ionizable lipids drive LNP immunogenicity by binding to Toll-like receptor 4 and CD1d and by promoting lipid-raft formation. Immunogenic LNPs favour a type-1 T-helper-cell-biased immune response marked by increases in the immunoglobulins IgG2c and IgG1 and in the pro-inflammatory cytokines tumour necrosis factor, interferon γ and the interleukins IL-6 and IL-2. Notably, the inflammatory signals originating from these receptors inhibit the production of anti-poly(ethylene glycol) IgM antibodies, preventing the often-observed loss of efficacy in the LNP-mediated delivery of siRNA and mRNA. Moreover, we identified computational methods for the prediction of the structure-dependent innate and adaptive responses of LNPs. Our findings may help accelerate the discovery of well-tolerated ionizable lipids suitable for repeated dosing.
Indexed as
Identifiers
What OpenQuestion holds
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.