ArticleNucleic acids research2020
Fetal antisense oligonucleotide therapy for congenital deafness and vestibular dysfunction.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 37 citations in OpenAlex.
- Recent preclinical and clinical advances in gene therapy for hereditary hearing loss.Molecules and cells · 2025Review
- NADScience advances · 2025Article
- In utero therapy for spinal muscular atrophy: closer to clinical translation.Brain : a journal of neurology · 2025Review
- Hearing loss: a global view for gene therapy approaches and challenges.European journal of pediatrics · 2025Review
- The power of mouse models in the diagnostic odyssey of patients with rare congenital anomalies.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Advancing precision ear medicine: leveraging animal models for disease insights and therapeutic innovations.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy.Science translational medicine · 2025Article
- Inner Ear Gene Therapy: An Overview from Bench to Bedside.Molecular diagnosis & therapy · 2025Review
- Current approaches for Usher syndrome disease models and developing therapies.Frontiers in cell and developmental biology · 2025Review
- Prenatal delivery of a therapeutic antisense oligonucleotide achieves broad biodistribution in the brain and ameliorates Angelman syndrome phenotype in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss.Biomedicines · 2023Review
- Gene Therapy for Inherited Hearing Loss: Updates and Remaining Challenges.Audiology research · 2023Review
- Deafness: from genetic architecture to gene therapy.Nature reviews. Genetics · 2023Review
- Advances in gene therapy hold promise for treating hereditary hearing loss.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- The Genomics of Auditory Function and Disease.Annual review of genomics and human genetics · 2022Review
- Conversations in Cochlear Implantation: The Inner Ear Therapy of Today.Biomolecules · 2022Review
- Central auditory deficits associated with genetic forms of peripheral deafness.Human genetics · 2022Review
- Vestibular Deficits in Deafness: Clinical Presentation, Animal Modeling, and Treatment Solutions.Frontiers in neurology · 2022Review
- The landscape and biological relevance of aberrant alternative splicing events in esophageal squamous cell carcinoma.Oncogene · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Disabling hearing loss impacts ∼466 million individuals worldwide with 34 million children affected. Gene and pharmacotherapeutic strategies to rescue auditory function in mouse models of human deafness are most effective when administered before hearing onset, after which therapeutic efficacy is significantly diminished or lost. We hypothesize that preemptive correction of a mutation in the fetal inner ear prior to maturation of the sensory epithelium will optimally restore sensory function. We previously demonstrated that transuterine microinjection of a splice-switching antisense oligonucleotide (ASO) into the amniotic cavity immediately surrounding the embryo on embryonic day 13-13.5 (E13-13.5) corrected pre-mRNA splicing in the juvenile Usher syndrome type 1c (Ush1c) mouse mutant. Here, we show that this strategy only marginally rescues hearing and partially rescues vestibular function. To improve therapeutic outcomes, we microinjected ASO directly into the E12.5 inner ear. A single intra-otic dose of ASO corrects harmonin RNA splicing, restores harmonin protein expression in sensory hair cell bundles, prevents hair cell loss, improves hearing sensitivity, and ameliorates vestibular dysfunction. Improvements in auditory and vestibular function were sustained well into adulthood. Our results demonstrate that an ASO pharmacotherapeutic administered to a developing organ system in utero preemptively corrects pre-mRNA splicing to abrogate the disease phenotype.
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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.