ArticleNano letters2015
Self-Assembly into Nanoparticles Is Essential for Receptor Mediated Uptake of Therapeutic Antisense Oligonucleotides.
Article in Nano letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
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Who cites it
54 citing papers in PubMed, 96 citations in OpenAlex.
- Timing matters: Exon skipping therapy is most effective when initiated early in a mouse model of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2026Article
- Heteroduplex oligonucleotide technology boosts gene knockdown in cardiac and skeletal muscles.Nucleic acids research · 2026Article
- An unbiased whole-genome open reading frame overexpression screen identifies B3GALT2, a novel inducer of cellular ASO activity.Molecular therapy. Nucleic acids · 2025Article
- Immunostimulatory Effects of Guanine-Quadruplex Topologies as Scaffolds for CpG Oligodeoxynucleotides.Biomolecules · 2025Article
- Antisense phosphorodiamidate morpholino oligomers retain activity inFrontiers in microbiology · 2025Article
- Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction.International journal of molecular sciences · 2024Article
- Heteroduplex oligonucleotide technology boosts oligonucleotide splice switching activity of morpholino oligomers in a Duchenne muscular dystrophy mouse model.Nature communications · 2024Article
- THF peroxide as a factor in generating desulphurised products from the solid-phase synthesis of phosphorothioate-modified oligonucleotides.RSC advances · 2024Article
- Engineering circular RNA for molecular and metabolic reprogramming.Functional & integrative genomics · 2024Review
- Peptide Conjugates of a 2'-ACS omega · 2023Article
- Review
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- Structures and Applications of Nucleic Acid-Based Micelles for Cancer Therapy.International journal of molecular sciences · 2023Review
- Long Non-Coding RNAs in Pancreatic Cancer: Biologic Functions, Mechanisms, and Clinical Significance.Cancers · 2022Review
- Antisense Oligonucleotides Conjugated with Lipophilic Compounds: Synthesis and In Vitro Evaluation of Exon Skipping in Duchenne Muscular Dystrophy.International journal of molecular sciences · 2022Article
- Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides.Communications biology · 2022Article
- Synthesis and Exon-Skipping Properties of a 3'-Ursodeoxycholic Acid-Conjugated Oligonucleotide TargetingMolecules (Basel, Switzerland) · 2021Article
- Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles.ACS nano · 2021Review
- Targeting circular RNAs as a therapeutic approach: current strategies and challenges.Signal transduction and targeted therapy · 2021Review
- Fine Tuning of Phosphorothioate Inclusion in 2'-O-Methyl Oligonucleotides Contributes to Specific Cell Targeting for Splice-Switching Modulation.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 7 countries.
Funding
Abstract
Antisense oligonucleotides (ASOs) have the potential to revolutionize medicine due to their ability to manipulate gene function for therapeutic purposes. ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake, however, a major challenge is the poor understanding of their uptake mechanisms, which would facilitate improved ASO designs with enhanced activity and reduced toxicity. Here, we study the uptake mechanism of three therapeutically relevant ASOs (peptide-conjugated phosphorodiamidate morpholino (PPMO), 2'Omethyl phosphorothioate (2'OMe), and phosphorothioated tricyclo DNA (tcDNA) that have been optimized to induce exon skipping in models of Duchenne muscular dystrophy (DMD). We show that PPMO and tcDNA have high propensity to spontaneously self-assemble into nanoparticles. PPMO forms micelles of defined size and their net charge (zeta potential) is dependent on the medium and concentration. In biomimetic conditions and at low concentrations, PPMO obtains net negative charge and its uptake is mediated by class A scavenger receptor subtypes (SCARAs) as shown by competitive inhibition and RNAi silencing experiments in vitro. In vivo, the activity of PPMO was significantly decreased in SCARA1 knockout mice compared to wild-type animals. Additionally, we show that SCARA1 is involved in the uptake of tcDNA and 2'OMe as shown by competitive inhibition and colocalization experiments. Surface plasmon resonance binding analysis to SCARA1 demonstrated that PPMO and tcDNA have higher binding profiles to the receptor compared to 2'OMe. These results demonstrate receptor-mediated uptake for a range of therapeutic ASO chemistries, a mechanism that is dependent on their self-assembly into nanoparticles.
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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.