ArticleJCI insight2021
Antisense oligonucleotide treatment rescues UBE3A expression and multiple phenotypes of an Angelman syndrome mouse model.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 80 citations in OpenAlex.
- Emerging Therapies for Angelman Syndrome.CNS drugs · 2026Review
- Review
- RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine.International journal of molecular sciences · 2026Review
- Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression.Molecular therapy. Nucleic acids · 2026Review
- Operant behavior is reliably impaired in a mouse model of Angelman syndrome.Research square · 2026Article
- A dual-reporter mouse for therapeutic discovery in Angelman syndrome.JCI insight · 2026Article
- Crossing the finish line towards a disease-modifying treatment for Angelman syndrome.Journal of neurodevelopmental disorders · 2026Review
- A xenotransplantation model for reactivation of paternal UBE3A using human-specific antisense oligonucleotides.Scientific reports · 2026Article
- RNAi-Induced Expression of Paternal UBE3A.Genes · 2026Article
- Challenges and emerging strategies for genome-wide evaluation of loss of imprinting in cancer.British journal of biomedical science · 2026Review
- Genetic medicines for epilepsy: unlocking new avenues for seizure control.Frontiers in bioengineering and biotechnology · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- UBE3A stabilization of β-catenin preserves synaptic proteins essential for motor and cognitive functions in Angelman Syndrome.Molecular autism · 2025Article
- Article
- Courtship and distress ultrasonic vocalizations are altered in a mouse model of Angelman syndrome.Journal of neurodevelopmental disorders · 2025Article
- AAV-dCas9 vector unsilences paternal Ube3a in neurons by impeding Ube3a-ATS transcription.Communications biology · 2025Article
- The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a phase 1 trial.Nature medicine · 2025Article
- Article
- UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects.Molecular autism · 2025Article
- Angelman syndrome patient-derived neuron screen leads to clinical ASO rugonersen targeting UBE3A-ATS with long-lasting effect in monkeys.Nucleic acids research · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angelman syndrome (AS) is a severe neurodevelopmental disorder for which only symptomatic treatment with limited benefits is available. AS is caused by mutations affecting the maternally inherited ubiquitin protein ligase E3A (UBE3A) gene. Previous studies showed that the silenced paternal Ube3a gene can be activated by targeting the antisense Ube3a-ATS transcript. We investigated antisense oligonucleotide-induced (ASO-induced) Ube3a-ATS degradation and its ability to induce UBE3A reinstatement and rescue of AS phenotypes in an established Ube3a mouse model. We found that a single intracerebroventricular injection of ASOs at postnatal day 1 (P1) or P21 in AS mice resulted in potent and specific UBE3A reinstatement in the brain, with levels up to 74% of WT levels in the cortex and a full rescue of sensitivity to audiogenic seizures. AS mice treated with ASO at P1 also showed rescue of established AS phenotypes, such as open field and forced swim test behaviors, and significant improvement on the reversed rotarod. Hippocampal plasticity of treated AS mice was comparable to WT but not significantly different from PBS-treated AS mice. No rescue was observed for the marble burying and nest building phenotypes. Our findings highlight the promise of ASO-mediated reactivation of UBE3A as a disease-modifying treatment for AS.
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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.