ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Endocytic Profiling of Cancer Cell Models Reveals Critical Factors Influencing LNP-Mediated mRNA Delivery and Protein Expression.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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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.
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Who cites it
59 citing papers in PubMed, 103 citations in OpenAlex.
- Low reactogenicity and high tumour antigen expression from mRNA-LNPs with membrane-destabilizing zwitterionic lipids.Nature biomedical engineering · 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
- From Morphology to Mechanism: Cryo-Electron Microscopy Insights into Lipid Nanoparticles for RNA Delivery.ACS nano · 2026Review
- mRNA Lipid Nanoparticles for Cell Engineering in Vivo and in Vitro: Current Applications and Future Directions.MedComm · 2026Review
- Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution.Acta pharmaceutica Sinica. B · 2026Review
- The Emerging Role of Nanocarrier-Based Delivery Systems for cGAS-STING Activation in Cancer Immunotherapy.International journal of nanomedicine · 2026Review
- Article
- mRNA therapeutics: Transforming medicine through innovation in design, delivery, and disease treatment.Molecular therapy. Nucleic acids · 2025Review
- Effects of disaccharide and cationic lipid types on reverse transfection with lyophilized mRNA lipoplexes.Experimental and therapeutic medicine · 2025Article
- Machine learning-assisted design of immunomodulatory lipid nanoparticles for delivery of mRNA to repolarize hyperactivated microglia.Drug delivery · 2025Article
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- Targeting and tracking mRNA lipid nanoparticles at the particle, transcript and protein level.Nature biomedical engineering · 2025Review
- Rational design of lipid nanoparticles for enabling gene therapies.Molecular therapy. Methods & clinical development · 2025Review
- Modulating Immunogenicity and Reactogenicity in mRNA-Lipid Nanoparticle Vaccines through Lipid Component Optimization.ACS nano · 2025Article
- Investigation of the impact of lipid nanoparticle compositions on the delivery and T cell response of circRNA vaccine.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Cubic Phase-Inducible Zwitterionic Phospholipids Improve the Functional Delivery of mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver.Journal of medicinal chemistry · 2025Review
- Exploring the Challenges of Lipid Nanoparticle Development: The In Vitro-In Vivo Correlation Gap.Vaccines · 2025Article
- CD47 Knock-Out Using CRISPR-Cas9 RNA Lipid Nanocarriers Results in Reduced Mesenchymal Glioblastoma Growth In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome.Advanced drug delivery reviews · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Lipid nanoparticles have great potential for delivering nucleic-acid-based therapeutics, but low efficiency limits their broad clinical translation. Differences in transfection capacity between in vitro models used for nanoparticle pre-clinical testing are poorly understood. To address this, using a clinically relevant lipid nanoparticle (LNP) delivering mRNA, we highlight specific endosomal characteristics in in vitro tumor models that impact protein expression. A 30-cell line LNP-mRNA transfection screen identified three cell lines having low, medium, and high transfection that correlated with protein expression when they were analyzed in tumor models. Endocytic profiling of these cell lines identified major differences in endolysosomal morphology, localization, endocytic uptake, trafficking, recycling, and endolysosomal pH, identified using a novel pH probe. High-transfecting cells showed rapid LNP uptake and trafficking through an organized endocytic pathway to lysosomes or rapid exocytosis. Low-transfecting cells demonstrated slower endosomal LNP trafficking to lysosomes and defective endocytic organization and acidification. Our data establish that efficient LNP-mRNA transfection relies on an early and narrow endosomal escape window prior to lysosomal sequestration and/or exocytosis. Endocytic profiling should form an important pre-clinical evaluation step for nucleic acid delivery systems to inform model selection and guide delivery-system design for improved clinical translation.
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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.