ArticleNature communications2024
Ube3a unsilencer for the potential treatment of Angelman syndrome.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Emerging Therapies for Angelman Syndrome.CNS drugs · 2026Review
- RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine.International journal of molecular sciences · 2026Review
- A patient-specific induced pluripotent stem cell and neural stem cell resource for angelman syndrome with 15q11.2-q13 deletion.Scientific reports · 2026Article
- UBE3A isoform-selective and non-selective contributions to Angelman syndrome phenotypes.Molecular psychiatry · 2026Article
- Toward a Small Molecule Therapy for Angelman Syndrome: Structure-Activity Relationship Studies of 3-Aminopyrazole Phenylacetamides as PaternalJournal of medicinal chemistry · 2026Article
- Targeting UBE3A and downstream estrogen receptor-β signaling to restore oligodendroglial homeostasis in Angelman syndrome.bioRxiv : the preprint server for biology · 2026Article
- 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
- Challenges and emerging strategies for genome-wide evaluation of loss of imprinting in cancer.British journal of biomedical science · 2026Review
- Mouse model of Angelman syndrome exhibits reduced retinal activity during development.Frontiers in neuroscience · 2026Article
- Multi-targeting zinc finger nuclease vector unsilences paternal UBE3A in a mouse model of Angelman syndrome.Gene therapy · 2026Article
- Antisense oligonucleotide therapy mitigates autosomal dominant progressive hearing loss in a murine model of human DFNA2.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Courtship and distress ultrasonic vocalizations are altered in a mouse model of Angelman syndrome.Journal of neurodevelopmental disorders · 2025Article
- A stem cell-based toolkit to model Angelman syndrome caused by paternal uniparental disomy of chromosome 15.Human cell · 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
- Therapeutic strategies for fragile X syndrome and implications for other gene-silencing disorders.Nature genetics · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Deletion of the maternal UBE3A allele causes Angelman syndrome (AS); because paternal UBE3A is epigenetically silenced by a long non-coding antisense (UBE3A-ATS) in neurons, this nearly eliminates UBE3A protein in the brain. Reactivating paternal UBE3A holds promise for treating AS. We previously showed topoisomerase inhibitors can reactivate paternal UBE3A, but their therapeutic challenges prompted our search for small molecule unsilencers with a different mechanism of action. Here, we found that (S)-PHA533533 acts through a novel mechanism to significantly increase paternal Ube3a mRNA and UBE3A protein levels while downregulating Ube3a-ATS in primary neurons derived from AS model mice. Furthermore, peripheral delivery of (S)-PHA533533 in AS model mice induces widespread neuronal UBE3A expression. Finally, we show that (S)-PHA533533 unsilences paternal UBE3A in AS patient-derived neurons, highlighting its translational potential. Our findings provide a lead for developing a small molecule treatment for AS that could be safe, non-invasively delivered, and capable of brain-wide unsilencing of paternal UBE3A.
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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.