ArticleMolecular therapy. Nucleic acids2015
Histone-targeted Polyplexes Avoid Endosomal Escape and Enter the Nucleus During Postmitotic Redistribution of ER Membranes.
Article in Molecular therapy. Nucleic acids, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed.
- One-Step Microfluidic Manufactured Fucose-Decorated Sweetosomes Choose the Time and the Road for Their Intracellular Journey to Cancer Treatment.Advanced healthcare materials · 2026Article
- Achieving Endo/Lysosomal Escape Using Smart Nanosystems for Efficient Cellular Delivery.Molecules (Basel, Switzerland) · 2024Review
- Size-Related Pathway Flux Analysis of Ultrasmall Iron Oxide Nanoparticles in Macrophage Cell RAW264.7 for Safety Evaluation.ACS omega · 2024Article
- Summary report of the 1st MOVE symposium in Málaga from 24-27th October 2023 - Foster the European mobility for young scientists in extracellular vesicles research.Extracellular vesicles and circulating nucleic acids · 2024Article
- Exocytosis of Nanoparticles: A Comprehensive Review.Nanomaterials (Basel, Switzerland) · 2023Review
- Design of Nanohydrogels for Targeted Intracellular Drug Transport to the Trans-Golgi Network.Advanced healthcare materials · 2023Article
- Engineering poly- and micelleplexes for nucleic acid delivery - A reflection on their endosomal escape.Journal of controlled release : official journal of the Controlled Release Society · 2023Review
- Bacteriophage T4 as a nanovehicle for delivery of genes and therapeutics into human cells.Current opinion in virology · 2022Review
- Tetraethylenepentamine-Coated β Cyclodextrin Nanoparticles for Dual DNA and siRNA Delivery.Pharmaceutics · 2022Article
- Efficiency of Cytosolic Delivery with Poly(β-amino ester) Nanoparticles is Dependent on the Effective pACS biomaterials science & engineering · 2020Article
- Regulating intracellular fate of siRNA by endoplasmic reticulum membrane-decorated hybrid nanoplexes.Nature communications · 2019Article
- Brief update on endocytosis of nanomedicines.Advanced drug delivery reviews · 2019Review
- Gene delivery by peptide-assisted transport.Current opinion in biomedical engineering · 2018Article
- Histone-targeted gene transfer of bone morphogenetic protein-2 enhances mesenchymal stem cell chondrogenic differentiation.Acta biomaterialia · 2018Article
- In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes.Proteome science · 2018Article
- A Triple-Fluorophore-Labeled Nucleic Acid pH Nanosensor to Investigate Non-viral Gene Delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Efficient tuning of siRNA dose response by combining mixed polymer nanocarriers with simple kinetic modeling.Acta biomaterialia · 2017Article
- Overexpression of caveolin-1 in inflammatory breast cancer cells enables IBC-specific gene delivery and prodrug conversion using histone-targeted polyplexes.Biotechnology and bioengineering · 2016Article
- Journey to the Center of the Cell: Current Nanocarrier Design Strategies Targeting Biopharmaceuticals to the Cytoplasm and Nucleus.Current pharmaceutical design · 2016Review
- Importin-4 Regulates Gene Delivery by Enhancing Nuclear Retention and Chromatin Deposition by Polyplexes.Molecular pharmaceutics · 2015Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Nonviral gene delivery is a promising therapeutic approach because of its safety and controllability, yet limited gene transfer efficacy is a common issue. Most nonviral strategies rely upon endosomal escape designs; however, endosomal escape is often uncorrelated with improved gene transfer and membranolytic structures are typically cytotoxic. Previously, we showed that histone-targeted polyplexes trafficked to the nucleus through an alternative route involving caveolae and the Golgi and endoplasmic reticulum (ER), using pathways similar to several pathogens. We hypothesized that the efficacy of these polyplexes was due to an increased utilization of native vesicular trafficking as well as regulation by histone effectors. Accordingly, using confocal microscopy and cellular fractionation, we determined that a key effect of histone-targeting was to route polyplexes away from clathrin-mediated recycling pathways by harnessing endomembrane transfer routes regulated by histone methyltransferases. An unprecedented finding was that polyplexes accumulated in Rab6-labeled Golgi/ER vesicles and ultimately shuttled directly into the nucleus during ER-mediated nuclear envelope reassembly. Specifically, super resolution microscopy and fluorescence correlation spectroscopy unequivocally indicated that the polyplexes remained associated with ER vesicles/membranes until mitosis, when they were redistributed into the nucleus. These novel findings highlight alternative mechanisms to subvert endolysosomal trafficking and harness the ER to enhance gene transfer.
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Registered trials
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