ArticleNature communications2021
Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Exploratory Analysis of ELP1 Expression in Whole Blood From Patients With Familial Dysautonomia.Annals of clinical and translational neurology · 2026Article
- Utilization of Induced Pluripotent Stem Cell-Derived Neurons to Investigate the Splice-Modification Efficacy of Splice-Switching Drug Candidates.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing.Science advances · 2025Article
- Switching of OAS1 splicing isoforms overcomes SNP-derived vulnerability to SARS-CoV-2 infection.BMC biology · 2025Article
- Genipin rescues developmental and degenerative defects in familial dysautonomia models and accelerates axon regeneration.Science translational medicine · 2024Article
- Procyanidin B2 enhances anti-inflammatory responses of periodontal ligament cells by inhibiting the dominant negative pro-inflammatory isoforms of peroxisome proliferator-activated receptor γ.Journal of dental sciences · 2024Article
- Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.Experimental & molecular medicine · 2024Review
- Specificity, synergy, and mechanisms of splice-modifying drugs.Nature communications · 2024Article
- Neoantigens in cancer immunotherapy: focusing on alternative splicing.Frontiers in immunology · 2024Review
- Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure.PloS one · 2024Article
- Sonic hedgehog signaling: Alternative splicing and pathogenic role in medulloblastoma.Genes & diseases · 2023Review
- Article
- Familial dysautonomia.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2023Review
- The nexus between RNA-binding proteins and their effectors.Nature reviews. Genetics · 2023Review
- Targeting splicing factors for cancer therapy.RNA (New York, N.Y.) · 2023Article
- Phosphorylation mediated regulation of RNA splicing in plants.Frontiers in plant science · 2023Review
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- Principles and correction of 5'-splice site selection.RNA biology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Approximately half of genetic disease-associated mutations cause aberrant splicing. However, a widely applicable therapeutic strategy to splicing diseases is yet to be developed. Here, we analyze the mechanism whereby IKBKAP-familial dysautonomia (FD) exon 20 inclusion is specifically promoted by a small molecule splice modulator, RECTAS, even though IKBKAP-FD exon 20 has a suboptimal 5' splice site due to the IVS20 + 6 T > C mutation. Knockdown experiments reveal that exon 20 inclusion is suppressed in the absence of serine/arginine-rich splicing factor 6 (SRSF6) binding to an intronic splicing enhancer in intron 20. We show that RECTAS directly interacts with CDC-like kinases (CLKs) and enhances SRSF6 phosphorylation. Consistently, exon 20 splicing is bidirectionally manipulated by targeting cellular CLK activity with RECTAS versus CLK inhibitors. The therapeutic potential of RECTAS is validated in multiple FD disease models. Our study indicates that small synthetic molecules affecting phosphorylation state of SRSFs is available as a new therapeutic modality for mechanism-oriented precision medicine of splicing diseases.
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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.