ArticleJCI insight2021
Dual-isoform hUBE3A gene transfer improves behavioral and seizure outcomes in Angelman syndrome model mice.
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 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Emerging Therapies for Angelman Syndrome.CNS drugs · 2026Review
- 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
- Operant behavior is reliably impaired in a mouse model of Angelman syndrome.Research square · 2026Article
- Crossing the finish line towards a disease-modifying treatment for Angelman syndrome.Journal of neurodevelopmental disorders · 2026Review
- Multi-targeting zinc finger nuclease vector unsilences paternal UBE3A in a mouse model of Angelman syndrome.Gene therapy · 2026Article
- Article
- Restoration of NEXMIF expression rescues abnormalities in gene transcription, neuron maturation and autistic-like behaviors in Nexmif knockout mice.Translational psychiatry · 2025Article
- 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
- Article
- UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects.Molecular autism · 2025Article
- NEXMIF overexpression is associated with autism-like behaviors and alterations in dendritic arborization and spine formation in mice.Frontiers in neuroscience · 2025Article
- Understanding ubiquitination in neurodevelopment by integrating insights across space and time.Nature structural & molecular biology · 2025Review
- AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.Advanced drug delivery reviews · 2024Review
- Sex-biasing influence of autism-associatedScience advances · 2024Article
- Ube3a unsilencer for the potential treatment of Angelman syndrome.Nature communications · 2024Article
- Modelling phenotypes, variants and pathomechanisms of syndromic diseases in different systems.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2024Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Loss of the maternal UBE3A allele causes Angelman syndrome (AS), a debilitating neurodevelopmental disorder. Here, we devised an AS treatment strategy based on reinstating dual-isoform expression of human UBE3A (hUBE3A) in the developing brain. Kozak sequence engineering of our codon-optimized vector (hUBE3Aopt) enabled translation of both short and long hUBE3A protein isoforms at a near-endogenous 3:1 (short/long) ratio, a feature that could help to support optimal therapeutic outcomes. To model widespread brain delivery and early postnatal onset of hUBE3A expression, we packaged the hUBE3Aopt vector into PHP.B capsids and performed intracerebroventricular injections in neonates. This treatment significantly improved motor learning and innate behaviors in AS mice, and it rendered them resilient to epileptogenesis and associated hippocampal neuropathologies induced by seizure kindling. hUBE3A overexpression occurred frequently in the hippocampus but was uncommon in the neocortex and other major brain structures; furthermore, it did not correlate with behavioral performance. Our results demonstrate the feasibility, tolerability, and therapeutic potential for dual-isoform hUBE3A gene transfer in the treatment of 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.