ArticleNature communications2025
Cellular and biophysical barriers to lipid nanoparticle mediated delivery of RNA to the cytosol.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed.
- Lipid Nanoparticle-Mediated Delivery of CRISPR-Cas9 Components for Genome Editing.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Biologic Therapies for Alleviating Neurodegeneration in Lysosomal Storage Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Therapeutic cancer vaccines: development, challenges, and future perspectives.Acta pharmacologica Sinica · 2026Review
- Structural evolution of ionizable lipids for nucleic acid delivery.Nature reviews. Chemistry · 2026Review
- Research Advances on Organelle-Targeted Drug Delivery Systems for the Treatment of Brain Tumors and Central Nervous System Inflammation.Pharmaceutics · 2026Review
- Systemically delivered mRNA-LNPs transfect primary and secondary liver tumors.Molecular therapy. Nucleic acids · 2026Article
- Extracellular Vesicle-Lipid Hybrid Systems for RNA Delivery in Cancer: Structural Classification, Functional Delivery, and Translational Challenges.Pharmaceutics · 2026Review
- 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
- pH-Sensitive Amino Lipid-Driven Pore Formation Enables Endosomal Escape of Lipid Nanoparticles.Nature communications · 2026Article
- Membrane environment sets the functional pKBiophysical journal · 2026Article
- Identification of a cell subpopulation with different response to lipid nanoparticles and effect of protein corona on uptake and transfection.Materials today. Bio · 2026Article
- Dual targeting of mitochondrial metabolism and Rho GTPase signaling to suppress cancer metastasis (Review).Oncology reports · 2026Review
- Sequence-defined polymers for predictable gene delivery.Nature reviews. Chemistry · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Extracellular-Vesicle-Associated Nucleic Acids in the Diagnosis and Treatment of Respiratory Diseases: A Narrative Review.Pharmaceutics · 2026Review
- Construction of a translational whole-body physiologically based pharmacokinetic model to investigate the biodistribution of lipid nanoparticle-based mRNA therapeutics for intracellular protein targets.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Mechanistic Insight Into Ionizable Cationic Lipid-Mediated Endosomal Escape via Transient Lipid Complexes.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Small interfering RNA (siRNA)-based targeting breast cancer therapy.Discover oncology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Lipid nanoparticles (LNPs) are clinically approved for mRNA-based vaccines and liver-targeted siRNA delivery. However, poor nucleic acid delivery efficiency limits their application in extrahepatic tissues and tumors. Here, using live-cell and super-resolution microscopy, we identify multiple distinct steps of inefficiencies in the cytosolic delivery of both siRNA and mRNA cargoes. Membrane damages marked by galectin recruitment are conducive to cytosolic RNA release, whereas membrane perturbations recruiting the ESCRT machinery do not permit endosomal escape. Notably, only a small fraction of RNA is released from galectin-marked endosomes and, unexpectedly, many damaged endosomes contain no detectable RNA cargo. Using LNPs with both fluorescently labeled ionizable lipid and RNA, we show that these components segregate during endosomal sorting - both within single endosomes and across endosomal compartments. Finally, we visualize localized ionizable lipid enrichment in endosomal membranes and membrane damage in direct proximity to siRNA-LNPs tethered to luminal vesicle membranes. Taken together, our findings reveal multiple mechanistic barriers limiting intracellular RNA delivery by LNPs.
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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 Socratic graph.