ArticleMolecular therapy. Nucleic acids2019
Enhancing MicroRNA Activity through Increased Endosomal Release Mediated by Nigericin.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- A first-in-class EGFR-directed KRAS G12V selective inhibitor.Cancer cell · 2025Article
- Advances in miRNA research: Unraveling the complexities of gene regulation.Animal models and experimental medicine · 2025Review
- Targeted Delivery of miR-34a via Anti-CD47 Antibody Conjugates for Enhanced Cancer Immunotherapy in Triple Negative Breast Cancer.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent.Biochemical Society transactions · 2025Article
- Therapeutic Applications of Poly-miRNAs and miRNA Sponges.International journal of molecular sciences · 2025Review
- What will it take to get miRNA therapies to market?Nature biotechnology · 2024Article
- Disabled-2, a versatile tissue matrix multifunctional scaffold protein with multifaceted signaling: Unveiling its potential in the cancer battle.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- In Vitro Studies to Evaluate the Intestinal Permeation of an Ursodeoxycholic Acid-Conjugated Oligonucleotide for Duchenne Muscular Dystrophy Treatment.Pharmaceutics · 2024Article
- Selective targeting of chemically modified miR-34a to prostate cancer using a small molecule ligand and an endosomal escape agent.Molecular therapy. Nucleic acids · 2024Article
- Preparing and Evaluating the Stability of Therapeutically Relevant Oligonucleotide Duplexes.Bio-protocol · 2024Article
- miRNA-Based Technologies in Cancer Therapy.Journal of personalized medicine · 2023Review
- Tracking miRNA Release into Extracellular Vesicles using Flow Cytometry.Journal of visualized experiments : JoVE · 2023Article
- A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy.Oncogene · 2023Article
- Delivery of RNA Therapeutics: The Great Endosomal Escape!Nucleic acid therapeutics · 2022Review
- Tumor necrosis factor alpha delivers exogenous inflammation-related microRNAs to recipient cells with functional targeting capabilities.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Extracellular vesicles released by non-small cell lung cancer cells drive invasion and permeability in non-tumorigenic lung epithelial cells.Scientific reports · 2022Article
- Function and Therapeutic Implications of tRNA Derived Small RNAs.Frontiers in molecular biosciences · 2022Review
- Therapeutic potential of targeting mirnas to prostate cancer tumors: using psma as an active target.Molecular & cellular oncology · 2022Review
- Evolution of complexity in non-viral oligonucleotide delivery systems: from gymnotic delivery through bioconjugates to biomimetic nanoparticles.RNA biology · 2022Review
- MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The therapeutic promise of small-RNA therapeutics is limited, not only by the lack of delivery vehicles, but also by the inability of the small RNAs to reach intracellular compartments where they can be biologically active. We previously reported successful delivery of functionally active miRNAs via receptor-mediated endocytosis. This type of targeted therapy still faces a major challenge in the delivery field: endosomal sequestration. Here, a new method has been developed to promote endosomal escape of delivered miRNA. The strategy relies on the difference in solute contents between nascent endosomes and the cytoplasm; early endosomes are rich in sodium ions, whereas the intracellular fluid is rich is potassium ions. Exploiting this difference through favoring the influx of potassium into the endosomes without the exchange of osmotically active sodium, results in an osmotic differential leading to the endosomes swelling and bursting. One molecule that is able to exchange potassium for an osmotically inactive hydrogen ion is the ionophore nigericin. Through generating an intramolecular miRNA delivery vehicle, containing a ligand, in this case folate and nigericin, we enabled the escape of folate-RNA conjugates from their entrapping endosomes into the cytoplasm where they bound the RNA-induced silencing complex and activated the RNAi response.
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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.