ArticleNucleic acids research2012
Targeting a pre-mRNA structure with bipartite antisense molecules modulates tau alternative splicing.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines.Biochemistry · 2025Review
- Thermodynamic control of mismatch discrimination for extensive splicing regulation of PKM pre-mRNA.RNA (New York, N.Y.) · 2025Article
- From computational models of the splicing code to regulatory mechanisms and therapeutic implications.Nature reviews. Genetics · 2025Review
- An intronic RNA element modulates Factor VIII exon-16 splicing.Nucleic acids research · 2024Article
- Amyloid-beta peptide and tau protein crosstalk in Alzheimer's disease.Neural regeneration research · 2022Review
- RNA-based therapeutics for neurological diseases.RNA biology · 2022Review
- Therapeutic Modulation of RNA Splicing in Malignant and Non-Malignant Disease.Trends in molecular medicine · 2021Review
- RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays.Molecules (Basel, Switzerland) · 2021Review
- Alternative splicing in Alzheimer's disease.Aging clinical and experimental research · 2021Review
- Design, Optimization, and Study of Small Molecules That Target Tau Pre-mRNA and Affect Splicing.Journal of the American Chemical Society · 2020Article
- Progressive supranuclear palsy: Advances in diagnosis and management.Parkinsonism & related disorders · 2020Review
- Nuclear and Cytoplasmatic Quantification of Unconjugated, Label-Free Locked Nucleic Acid Oligonucleotides.Nucleic acid therapeutics · 2020Article
- RNA Secondary Structure-Based Design of Antisense Peptide Nucleic Acids for Modulating Disease-Associated Aberrant Tau Pre-mRNA Alternative Splicing.Molecules (Basel, Switzerland) · 2019Article
- RNA Splicing and Disease: Animal Models to Therapies.Trends in genetics : TIG · 2019Review
- Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids.Journal of visualized experiments : JoVE · 2017Article
- Emerging Diagnostic and Therapeutic Strategies for Tauopathies.Current neurology and neuroscience reports · 2017Review
- Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy.Nucleic acid therapeutics · 2017Article
- Nucleic Acid-Based Theranostics for Tackling Alzheimer's Disease.Theranostics · 2017Review
- The Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy.Molecular neurobiology · 2016Review
- Splice-switching antisense oligonucleotides as therapeutic drugs.Nucleic acids research · 2016Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Approximately 15% of human genetic diseases are estimated to involve dysregulation of alternative pre-mRNA splicing. Antisense molecules designed to alter these and other splicing events typically target continuous linear sequences of the message. Here, we show that a structural feature in a pre-mRNA can be targeted by bipartite antisense molecules designed to hybridize with the discontinuous elements that flank the structure and thereby alter splicing. We targeted a hairpin structure at the boundary between exon 10 and intron 10 of the pre-mRNA of tau. Mutations in this region that are associated with certain forms of frontotemporal dementia, destabilize the hairpin to cause increased inclusion of exon 10. Via electrophoretic mobility shift and RNase protection assays, we demonstrate that bipartite antisense molecules designed to simultaneously interact with the available sequences that immediately flank the tau pre-mRNA hairpin do indeed bind to this structured region. Moreover, these agents inhibit exon 10 splicing and reverse the effect of destabilizing disease-causing mutations, in both in vitro splicing assays and cell culture. This general bipartite antisense strategy could be employed to modulate other splicing events that are regulated by RNA secondary structure.
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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.