ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Regeneration of Cochlear Hair Cells and Hearing Recovery through Hes1 Modulation with siRNA Nanoparticles in Adult Guinea Pigs.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss.Nature communications · 2024Trial
- PLGA nanoparticles in otoprotection and inner ear regeneration: a new frontier in nanomedicine for hearing disorders.RSC advances · 2025Review
- Hearing restoration through hair cell regeneration: A review of recent advancements and current limitations.Hearing research · 2025Review
- Current AAV-mediated gene therapy in sensorineural hearing loss.Fundamental research · 2025Review
- Cochlear Mechanics Are Preserved After Inner Ear Delivery of Gold Nanoparticles.International journal of molecular sciences · 2024Article
- Strategies for non-viral vectors targeting organs beyond the liver.Nature nanotechnology · 2024Review
- Hair Cell Regeneration: From Animals to Humans.Clinical and experimental otorhinolaryngology · 2024Review
- Extracellular vesicles for developing targeted hearing loss therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Exploring delivery systems for targeted nanotechnology-based gene therapy in the inner ear.Therapeutic delivery · 2024Review
- Precision medicine: a new era for inner ear diseases.Frontiers in pharmacology · 2024Review
- Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss.Biomedicines · 2023Review
- Mapping of Notch signaling in the developing organ of Corti in common marmosets.Frontiers in neuroanatomy · 2023Article
- Rationally Designed Magnetic Nanoparticles for Cochlear Drug Delivery: Synthesis, Characterization, and In Vitro Biocompatibility in a Murine Model.Otology & neurotology open · 2022Article
- Hearing loss: The final frontier of pharmacology.Pharmacology research & perspectives · 2022Review
- Nanomaterials for Inner Ear Diseases: Challenges, Limitations and Opportunities.Materials (Basel, Switzerland) · 2022Review
- Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation.Human genetics · 2022Article
- Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities.Frontiers in neuroscience · 2022Review
- Molecular Pathways Modulating Sensory Hair Cell Regeneration in Adult Mammalian Cochleae: Progress and Perspectives.International journal of molecular sciences · 2021Review
- Nanoparticle-Based RNAi Therapeutics Targeting Cancer Stem Cells: Update and Prospective.Pharmaceutics · 2021Review
- Cochlea cell-specific marker expression upon in vitro Hes1 knockdown.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deafness is commonly caused by the irreversible loss of mammalian cochlear hair cells (HCs) due to noise trauma, toxins, or infections. We previously demonstrated that small interfering RNAs (siRNAs) directed against the Notch pathway gene, hairy and enhancer of split 1 (Hes1), encapsulated within biocompatible poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) could regenerate HCs within ototoxin-ablated murine organotypic cultures. In the present study, we delivered this sustained-release formulation of Hes1 siRNA (siHes1) into the cochleae of noise-injured adult guinea pigs. Auditory functional recovery was measured by serial auditory brainstem responses over a nine-week follow-up period, and HC regeneration was evaluated by immunohistological evaluations and scanning electron microscopy. Significant HC restoration and hearing recovery were observed across a broad tonotopic range in ears treated with siHes1 NPs, beginning at three weeks and extending out to nine weeks post-treatment. Moreover, both ectopic and immature HCs were uniquely observed in noise-injured cochleae treated with siHes1 NPs, consistent with de novo HC production. Our results indicate that durable cochlear HCs were regenerated and promoted significant hearing recovery in adult guinea pigs through reversible modulation of Hes1 expression. Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo.
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