ArticleThe Journal of cell biology2022
Endosomal escape of delivered mRNA from endosomal recycling tubules visualized at the nanoscale.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
What it found
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The trial behind it
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Who cites it
122 citing papers in PubMed, 178 citations in OpenAlex.
- BMP-7 mRNA delivered by Fibrin-CaP scaffolds activates osteogenic programs in vivo as evidenced by transcriptomic and proteomic analyses.Bioactive materials · 2026Article
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Research Advances on Organelle-Targeted Drug Delivery Systems for the Treatment of Brain Tumors and Central Nervous System Inflammation.Pharmaceutics · 2026Review
- Dual pKa Lipid Nanoparticles for Lung-tropic mRNA Delivery and pH-Programmed Endosomal Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.Nature nanotechnology · 2026Article
- EPHA2/CD44-directed trafficking enhances endosomal leakiness and antisense therapy delivery.The Journal of cell biology · 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
- Identification of a cell subpopulation with different response to lipid nanoparticles and effect of protein corona on uptake and transfection.Materials today. Bio · 2026Article
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Stimulus-Responsive Polymeric Carriers for Gene Delivery: Balancing Endosomal Escape with Nucleic Acid Release.Pharmaceutical research · 2026Review
- Genetic screening identifies WNT5A/RYK as a determinant of extracellular vesicle fate.Science advances · 2026Article
- Review
- Intraluminal Gold Nanoparticle-Loaded Liposomes Enable High-Resolution Nanoscale Mapping of Intracellular Delivery Pathways.ACS applied nano materials · 2026Article
- Polyplex of peptide-mannan and RNA for intranasal delivery of TGF-β siRNA in treatment of pulmonary fibrosis.Bioactive materials · 2026Article
- Engineered Lipid Nanoparticles with Promoted Endosomal Escape and R283S-Mediated Stimulator of Interferon Genes (STING) Activation for Pancreatic Cancer Immunotherapy.Pharmaceutics · 2026Article
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Mechanistic Insight Into Ionizable Cationic Lipid-Mediated Endosomal Escape via Transient Lipid Complexes.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Naked antisense oligonucleotides remain endolysosomally sequestered despite induced membrane damage.bioRxiv : the preprint server for biology · 2026Article
62 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
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delivery of exogenous mRNA using lipid nanoparticles (LNPs) is a promising strategy for therapeutics. However, a bottleneck remains in the poor understanding of the parameters that correlate with endosomal escape versus cytotoxicity. To address this problem, we compared the endosomal distribution of six LNP-mRNA formulations of diverse chemical composition and efficacy, similar to those used in mRNA-based vaccines, in primary human adipocytes, fibroblasts, and HeLa cells. Surprisingly, we found that total uptake is not a sufficient predictor of delivery, and different LNPs vary considerably in endosomal distributions. Prolonged uptake impaired endosomal acidification, a sign of cytotoxicity, and caused mRNA to accumulate in compartments defective in cargo transport and unproductive for delivery. In contrast, early endocytic/recycling compartments have the highest probability for mRNA escape. By using super-resolution microscopy, we could resolve a single LNP-mRNA within subendosomal compartments and capture events of mRNA escape from endosomal recycling tubules. Our results change the view of the mechanisms of endosomal escape and define quantitative parameters to guide the development of mRNA formulations toward higher efficacy and lower cytotoxicity.
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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.