ArticleHuman molecular genetics2018
Exon-specific U1 snRNAs improve ELP1 exon 20 definition and rescue ELP1 protein expression in a familial dysautonomia mouse model.
Article in Human molecular genetics, 2018. 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 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Exploratory Analysis of ELP1 Expression in Whole Blood From Patients With Familial Dysautonomia.Annals of clinical and translational neurology · 2026Article
- Prime editing of the common Familial Dysautonomia-causing c.2204 + 6T > C splicing mutation.Orphanet journal of rare diseases · 2026Article
- Exon-targeted U1 snRNA rescues splicing defects and ameliorates inherited optic neuropathy: A novel RNA-based treatment.Molecular therapy. Nucleic acids · 2026Article
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.International journal of retina and vitreous · 2025Review
- Utargetome: A targetome prediction tool for modified U1-snRNAs to identify distal-target positions with improved selectivity.PLoS computational biology · 2025Article
- tRNA Modifications: A Tale of Two Viruses-SARS-CoV-2 and ZIKV.International journal of molecular sciences · 2025Article
- Rescue of a panel of Hemophilia A-causing 5'ss splicing mutations by unique Exon-specific U1snRNA variants.Molecular medicine (Cambridge, Mass.) · 2025Article
- Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA.Molecular medicine (Cambridge, Mass.) · 2025Article
- Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia.bioRxiv : the preprint server for biology · 2024Article
- Genipin rescues developmental and degenerative defects in familial dysautonomia models and accelerates axon regeneration.Science translational medicine · 2024Article
- Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure.PloS one · 2024Article
- Characterization and Engineered U1 snRNA Rescue of Splicing Variants in a Turkish Neurodevelopmental Disease Cohort.Human mutation · 2024Article
- Development of Engineered-U1 snRNA Therapies: Current Status.International journal of molecular sciences · 2023Review
- Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects.Nature reviews. Genetics · 2023Review
- Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia.American journal of human genetics · 2023Article
- Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.American journal of human genetics · 2022Article
- Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia.Human molecular genetics · 2022Article
- OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spfMolecular medicine (Cambridge, Mass.) · 2021Article
- A Reporter Based Cellular Assay for Monitoring Splicing Efficiency.Journal of visualized experiments : JoVE · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Familial dysautonomia (FD) is a rare genetic disease with no treatment, caused by an intronic point mutation (c.2204+6T>C) that negatively affects the definition of exon 20 in the elongator complex protein 1 gene (ELP1 also known as IKBKAP). This substitution modifies the 5' splice site and, in combination with regulatory splicing factors, induces different levels of exon 20 skipping, in various tissues. Here, we evaluated the therapeutic potential of a novel class of U1 snRNA molecules, exon-specific U1s (ExSpeU1s), in correcting ELP1 exon 20 recognition. Lentivirus-mediated expression of ELP1-ExSpeU1 in FD fibroblasts improved ELP1 splicing and protein levels. We next focused on a transgenic mouse model that recapitulates the same tissue-specific mis-splicing seen in FD patients. Intraperitoneal delivery of ELP1-ExSpeU1s-adeno-associated virus particles successfully increased the production of full-length human ELP1 transcript and protein. This splice-switching class of molecules is the first to specifically correct the ELP1 exon 20 splicing defect. Our data provide proof of principle of ExSpeU1s-adeno-associated virus particles as a novel therapeutic strategy for FD.
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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.