ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Prenatal delivery of a therapeutic antisense oligonucleotide achieves broad biodistribution in the brain and ameliorates Angelman syndrome phenotype in mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Reappraising the topology of cell-free fetal DNA in maternal blood toward improved prenatal genetic diagnostics.Science advances · 2026Review
- Emerging Therapies for Angelman Syndrome.CNS drugs · 2026Review
- Review
- In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications.Journal of clinical medicine · 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
- Detection of Unlabeled Oligonucleotides in FFPE Tissue Sections Using Automated miRNAscope Assays.Methods in molecular biology (Clifton, N.J.) · 2026Article
- In utero precision medicine for severe, early-onset neurogenetic disease: scientific, clinical and ethical considerations.Pediatric research · 2025Article
- Courtship and distress ultrasonic vocalizations are altered in a mouse model of Angelman syndrome.Journal of neurodevelopmental disorders · 2025Article
- In utero therapy for spinal muscular atrophy: closer to clinical translation.Brain : a journal of neurology · 2025Review
- Advances in Fetal Surgery: A Narrative Review of Therapeutic Interventions and Future Directions.Medicina (Kaunas, Lithuania) · 2025Review
- Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy.Science translational medicine · 2025Article
- State-of-the-art gene therapy in epilepsy.Current opinion in neurology · 2025Review
- Forestwalk: A Machine Learning Workflow Brings New Insights Into Posture and Balance in Rodent Beam Walking.The European journal of neuroscience · 2025Article
- A human Angelman Syndrome class II pluripotent stem cell line with fluorescent paternalFrontiers in cell and developmental biology · 2025Article
- RNA-based therapies for neurodevelopmental disorders: innovative tools for molecular correction.Frontiers in molecular biosciences · 2025Review
- Review
- Ubiquitin system mutations in neurological diseases.Trends in biochemical sciences · 2024Review
- Ube3a unsilencer for the potential treatment of Angelman syndrome.Nature communications · 2024Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Angelman syndrome (AS), an early-onset neurodevelopmental disorder characterized by abnormal gait, intellectual disabilities, and seizures, occurs when the maternal allele of the UBE3A gene is disrupted, since the paternal allele is silenced in neurons by the UBE3A antisense (UBE3A-AS) transcript. Given the importance of early treatment, we hypothesized that prenatal delivery of an antisense oligonucleotide (ASO) would downregulate the murine Ube3a-AS, resulting in increased UBE3A protein and functional rescue. Using a mouse model with a Ube3a-YFP allele that reports on-target ASO activity, we found that in utero, intracranial (IC) injection of the ASO resulted in dose-dependent activation of paternal Ube3a, with broad biodistribution. Accordingly, in utero injection of the ASO in a mouse model of AS also resulted in successful restoration of UBE3A and phenotypic improvements in treated mice on the accelerating rotarod and fear conditioning. Strikingly, even intra-amniotic (IA) injection resulted in systemic biodistribution and high levels of UBE3A reactivation throughout the brain. These findings offer a novel strategy for early treatment of AS using an ASO, with two potential routes of administration in the prenatal window. Beyond AS, successful delivery of a therapeutic ASO into neurons has implications for a clinically feasible prenatal treatment for numerous neurodevelopmental disorders.
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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.