Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65

AAV2/Anc80L65; adeno-associated virus; gene therapy; hereditary deafness; in utero microinjection; inner ears; adeno associated virus vector; adeno associated virus vector Anc80L65; beta III tubulin; enhanced green fluorescent protein; myosin VIIa; transcription factor Sox2; tubulin; unclassified drug; Adeno associated virus 2; animal experiment; animal model; animal tissue; Article; auditory response; auditory threshold; brain stem response; cochlear nerve; controlled study; Corti organ; embryo; female; gene transfer; genetic transduction; inner ear; inner hair cell; microinjection; neuroepithelium; nonhuman; outer hair cell; perception deafness; prenatal period; priority journal; semicircular canal; spiral ganglion; sustentacular cell; vestibular hair cell; vestibule; viral gene delivery system

Abstract :

[en] This study demonstrates that Anc80L65, a synthetic AAV vector validated to exhibit high expression in the inner ears of neonatal and adult mice, can target both cochlear and vestibular hair cells and spiral ganglion neurons when delivered in utero. These findings support the potential use of Anc80L65 in prenatal gene therapy of hereditary hearing loss. © 2020 The Author(s); Sensorineural hearing loss is one of the most common sensory disorders worldwide. Recent advances in vector design have paved the way for investigations into the use of adeno-associated vectors (AAVs) for hearing disorder gene therapy. Numerous AAV serotypes have been discovered to be applicable to inner ears, constituting a key advance for gene therapy for sensorineural hearing loss, where transduction efficiency of AAV in inner ear cells is critical for success. One such viral vector, AAV2/Anc80L65, has been shown to yield high expression in the inner ears of mice treated as neonates or adults. Here, to evaluate the feasibility of prenatal gene therapy for deafness, we assessed the transduction efficiency of AAV2/Anc80L65-eGFP (enhanced green fluorescent protein) after microinjection into otocysts in utero. This embryonic delivery method achieved high transduction efficiency in both inner and outer hair cells of the cochlea. Additionally, the transduction efficiency was high in the hair cells of the vestibules and semicircular canals and in spiral ganglion neurons. Our results support the potential of Anc80L65 as a gene therapy vehicle for prenatal inner ear disorders. © 2020 The Author(s)

Disciplines :

Otolaryngology

Author, co-author :

Hu, C.-J.; Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan

Lu, Y.-C.; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

Tsai, Y.-H.; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan

Cheng, Haw-Yuan ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Institute of Brain Science, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan

Takeda, H.; Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear, Boston, MA, United States

Huang, C.-Y.; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, United States

Xiao, R.; Harvard Stem Cell Institute, Cambridge, MA, United States

Hsu, C.-J.; Broad Institute of MIT and Harvard, Cambridge, MA, United States

Tsai, J.-W.; Department of Ophthalmology, Harvard Medical School, Boston, MA, United States

Vandenberghe, L.H.; Department of Medical Research, National Taiwan University Hospital Biomedical Park Hospital, Hsinchu, Taiwan

Wu, C.-C.; Department of Otolaryngology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan

Cheng, Y.-F.; Brain Research Center, National Yang-Ming University, Taipei, Taiwan

Language :

English

Title :

Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65

Publication date :

2020

Journal title :

Molecular Therapy: Methods and Clinical Development

eISSN :

2329-0501

Publisher :

Cell Press

Volume :

Pages :

493 - 500

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85088651043&doi=10.1016%2fj.omtm.2020.06.019&partnerID=40&md5=e16d1d1a6516aa71d6ba822554661c3a

Available on ORBi :

since 14 April 2025

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