ArticleAmerican journal of human genetics2022
Rescue of a familial dysautonomia mouse model by AAV9-Exon-specific U1 snRNA.
Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- ELP1 gene augmentation restores visual function in a mouse model of familial dysautonomia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Peripheral neuron phenotypes of familial dysautonomia are rescued by AAV-mediated gene therapy.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- Exploratory Analysis of ELP1 Expression in Whole Blood From Patients With Familial Dysautonomia.Annals of clinical and translational neurology · 2026Article
- Article
- Prime editing of the common Familial Dysautonomia-causing c.2204 + 6T > C splicing mutation.Orphanet journal of rare diseases · 2026Article
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Molecular mechanisms and therapeutic strategies for the recurrent F9 (c.520 + 13 A > G) variant in hemophilia B.Human genomics · 2026Article
- RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.International journal of retina and vitreous · 2025Review
- Peripheral neuron phenotypes of familial dysautonomia are rescued by AAV-mediated gene therapy.Research square · 2025Article
- Rescue of a panel of Hemophilia A-causing 5'ss splicing mutations by unique Exon-specific U1snRNA variants.Molecular medicine (Cambridge, Mass.) · 2025Article
- Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia.bioRxiv : the preprint server for biology · 2024Article
- Linking the Extended Autonomic System with the Homeostat Theory: New Perspectives about Dysautonomias.Journal of personalized 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
- Familial dysautonomia.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 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
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Familial dysautonomia (FD) is a currently untreatable, neurodegenerative disease caused by a splicing mutation (c.2204+6T>C) that causes skipping of exon 20 of the elongator complex protein 1 (ELP1) pre-mRNA. Here, we used adeno-associated virus serotype 9 (AAV9-U1-FD) to deliver an exon-specific U1 (ExSpeU1) small nuclear RNA, designed to cause inclusion of ELP1 exon 20 only in those cells expressing the target pre-mRNA, in a phenotypic mouse model of FD. Postnatal systemic and intracerebral ventricular treatment in these mice increased the inclusion of ELP1 exon 20. This also augmented the production of functional protein in several tissues including brain, dorsal root, and trigeminal ganglia. Crucially, the treatment rescued most of the FD mouse mortality before one month of age (89% vs 52%). There were notable improvements in ataxic gait as well as renal (serum creatinine) and cardiac (ejection fraction) functions. RNA-seq analyses of dorsal root ganglia from treated mice and human cells overexpressing FD-ExSpeU1 revealed only minimal global changes in gene expression and splicing. Overall then, our data prove that AAV9-U1-FD is highly specific and will likely be a safe and effective therapeutic strategy for this debilitating disease.
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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.