ArticleNature genetics2020
A slipped-CAG DNA-binding small molecule induces trinucleotide-repeat contractions in vivo.
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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
69 citing papers in PubMed, 146 citations in OpenAlex.
- Short Tandem Repeat 3D Structure Database (STR3SD): A Resource for Structural Biology Research of Short Tandem Repeats in Neurodegenerative Disorders.International journal of molecular sciences · 2026Review
- DNA-DETR: sequence representation matters in object detection for functional genomic elements.Briefings in bioinformatics · 2026Article
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Small Molecule Modulation of APOBEC3A-Catalyzed Cytosine Deamination in CCG Repeat Deoxyribonucleic Acid via Stabilization of Hairpin Structures.Biochemistry · 2025Article
- Base excision repair within structure-forming repeat sequences and its impact on cancer and other diseases.NAR cancer · 2025Review
- Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.Nature communications · 2025Article
- Challenges in Polyglutamine Diseases: From Dysfunctional Neuronal Circuitries to Neuron-Specific CAG Repeat Instability.International journal of molecular sciences · 2025Review
- Naphthyridine carbamate dimer ligand induces formation of Z-RNA-like fold of disease-related RNA and exhibits a molecular glue characteristics in crystal lattice formation.Nucleic acids research · 2025Article
- Molecular genetics of myotonic dystrophy and the evolution of therapeutic approaches.Journal of human genetics · 2025Review
- NMR-Based Rational Drug Design of G:G Mismatch DNA Binding Ligand Trapping Transient Complex via Disruption of a Key Allosteric Interaction.Journal of the American Chemical Society · 2025Article
- Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.bioRxiv : the preprint server for biology · 2025Article
- Navigating triplet repeats sequencing: concepts, methodological challenges and perspective for Huntington's disease.Nucleic acids research · 2025Review
- Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases.Biomolecules · 2024Review
- Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent.NAR molecular medicine · 2024Article
- Antisense RNA C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms a triplex-like structure and binds small synthetic ligand.Nucleic acids research · 2024Article
- Review
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Structural investigation of pathogenic RFC1 AAGGG pentanucleotide repeats reveals a role of G-quadruplex in dysregulated gene expression in CANVAS.Nucleic acids research · 2024Article
- Novel genotype-phenotype correlations, differential cerebellar allele-specific methylation, and a common origin of the (ATTTC)Human genetics · 2024Article
- Massive contractions of myotonic dystrophy type 2-associated CCTG tetranucleotide repeats occur via double-strand break repair with distinct requirements for DNA helicases.G3 (Bethesda, Md.) · 2024Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
32 authors at 9 institutions in 4 countries.
Funding
Abstract
In many repeat diseases, such as Huntington's disease (HD), ongoing repeat expansions in affected tissues contribute to disease onset, progression and severity. Inducing contractions of expanded repeats by exogenous agents is not yet possible. Traditional approaches would target proteins driving repeat mutations. Here we report a compound, naphthyridine-azaquinolone (NA), that specifically binds slipped-CAG DNA intermediates of expansion mutations, a previously unsuspected target. NA efficiently induces repeat contractions in HD patient cells as well as en masse contractions in medium spiny neurons of HD mouse striatum. Contractions are specific for the expanded allele, independently of DNA replication, require transcription across the coding CTG strand and arise by blocking repair of CAG slip-outs. NA-induced contractions depend on active expansions driven by MutSβ. NA injections in HD mouse striatum reduce mutant HTT protein aggregates, a biomarker of HD pathogenesis and severity. Repeat-structure-specific DNA ligands are a novel avenue to contract expanded repeats.
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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.