ArticleNucleic acids research2014
Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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
49 citing papers in PubMed, 83 citations in OpenAlex.
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- Survivin-Targeting Antisense Oligonucleotides in Cancer Therapy.Molecules (Basel, Switzerland) · 2026Review
- Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Advancements in RNA-based therapies from bench to bedside.npj drug discovery · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Review
- Preclinical evaluation of antisense oligonucleotide therapy in a mouse model ofbioRxiv : the preprint server for biology · 2025Article
- Unveiling the regulatory potential of the non-coding genome: Insights from the human genome project to precision medicine.Genes & diseases · 2025Review
- Application of Antisense Oligonucleotides as an Alternative Approach for Gene Expression Control and Functional Studies.International journal of molecular sciences · 2025Review
- uORF-targeting steric block antisense oligonucleotides do not reproducibly increase RNASEH1 expression.Molecular therapy. Nucleic acids · 2025Article
- Lipid Nanovesicles in Cancer Treatment: Improving Targeting and Stability of Antisense Oligonucleotides.Drug design, development and therapy · 2025Review
- Current landscape for the management of facioscapulohumeral muscular dystrophy and emerging treatment modalities: A literature review.AIMS neuroscience · 2025Review
- Technologies for Targeted RNA Degradation and Induced RNA Decay.Chemical reviews · 2024Review
- Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape.International journal of molecular sciences · 2024Review
- Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.Acta pharmacologica Sinica · 2024Article
- RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.Molecular therapy. Nucleic acids · 2024Review
- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- RNA-based medicine: from molecular mechanisms to therapy.The EMBO journal · 2023Review
- Drug Discovery Perspectives of Antisense Oligonucleotides.Biomolecules & therapeutics · 2023Review
- Antisense oligonucleotides: a novel Frontier in pharmacological strategy.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antisense oligonucleotides (ASOs) are synthetic oligonucleotides that alter expression of disease-associated transcripts via Watson-Crick hybridization. ASOs that function through RNase H or the RNA-induced silencing complex (RISC) result in enzymatic degradation of target RNA. ASOs designed to sterically block access of proteins to the RNA modulate mRNA metabolism but do not typically cause degradation. Here, we rationally design steric blocking ASOs to promote mRNA reduction and characterize the terminating mechanism. Transfection of ASOs complementary to constitutive exons in STAT3 and Sod1 results in greater than 70% reduction of mRNA and protein. The ASOs promote aberrant exon skipping and generation of premature termination codon (PTC)-containing mRNAs. We inhibit the nonsense-mediated mRNA decay (NMD) pathway and show that the PTC-containing mRNAs are recognized by the UPF1 ATPase, cleaved by the SMG6 endonuclease and degraded by the XRN1 cytoplasmic exonuclease. NMD surveillance, however, does not entirely explain the mechanism of decreased STAT3 expression. In addition to exon skipping, ASO treatment causes intron retention and reduction of chromatin-associated STAT3 mRNA. The application of steric blocking ASOs to promote RNA degradation allows one to explore more nucleotide modifications than tolerated by RNase H or RISC-dependent ASOs, with the goal of improving ASO drug properties.
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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.