ArticleCell2022
Counteracting chromatin effects of a splicing-correcting antisense oligonucleotide improves its therapeutic efficacy in spinal muscular atrophy.
Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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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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
48 citing papers in PubMed, 71 citations in OpenAlex.
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026Review
- A rare 5'UTR variant in SEC24D reveals translational dysfunction in osteogenesis imperfecta: a roadmap for RNA therapeutic rescue.Scientific reports · 2026Article
- Modulating microtubule stability via α-tubulin acetylation partially restores Golgi fragmentation in spinal muscular atrophy.Turkish journal of biology = Turk biyoloji dergisi · 2026Article
- A therapeutic antisense oligonucleotide encompassing 2'-NAR molecular medicine · 2026Article
- 10H-phenothiazine exerts beneficial effects in spinal muscular atrophy in vitro and in vivo models.Scientific reports · 2025Article
- Bridge Nucleic Acid/DNA Gapmers as Potential Inhibitors of Bacterial Gene Expression by Multiple Antisense Mechanisms: An In Vitro Study.Molecules (Basel, Switzerland) · 2025Article
- Review
- Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.Nature communications · 2025Article
- Bridge nucleic acid/DNA gapmers as inhibitors of gene expression by multiple antisense mechanisms.Research square · 2025Article
- Epigenetic regulation in spinal muscular atrophy: emerging areas and future directions.Orphanet journal of rare diseases · 2025Review
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- Comprehensive analysis acrossiScience · 2025Article
- Article
- RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease.Journal of molecular biology · 2025Review
- Recombinant SMN protein synergizes with spinal muscular atrophy therapy to counteract pathological motor neuron phenotypes.Translational neurodegeneration · 2024Article
- Alternative splicing is coupled to gene expression in a subset of variably expressed genes.NPJ genomic medicine · 2024Article
- In Search of Spinal Muscular Atrophy Disease Modifiers.International journal of molecular sciences · 2024Review
- A De Novo Splicing Mutation ofInternational journal of molecular sciences · 2024Article
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is a motor-neuron disease caused by mutations of the SMN1 gene. The human paralog SMN2, whose exon 7 (E7) is predominantly skipped, cannot compensate for the lack of SMN1. Nusinersen is an antisense oligonucleotide (ASO) that upregulates E7 inclusion and SMN protein levels by displacing the splicing repressors hnRNPA1/A2 from their target site in intron 7. We show that by promoting transcriptional elongation, the histone deacetylase inhibitor VPA cooperates with a nusinersen-like ASO to promote E7 inclusion. Surprisingly, the ASO promotes the deployment of the silencing histone mark H3K9me2 on the SMN2 gene, creating a roadblock to RNA polymerase II elongation that inhibits E7 inclusion. By removing the roadblock, VPA counteracts the chromatin effects of the ASO, resulting in higher E7 inclusion without large pleiotropic effects. Combined administration of the nusinersen-like ASO and VPA in SMA mice strongly synergizes SMN expression, growth, survival, and neuromuscular function.
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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.