Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050120301431 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Chin-Ju Hu Ying-Chang Lu Yi-Hsiu Tsai Haw-Yuan Cheng Hiroki Takeda Chun-Ying Huang Ru Xiao Chuan-Jen Hsu Jin-Wu Tsai Luk H. Vandenberghe Chen-Chi Wu Yen-Fu Cheng |
| spellingShingle |
Chin-Ju Hu Ying-Chang Lu Yi-Hsiu Tsai Haw-Yuan Cheng Hiroki Takeda Chun-Ying Huang Ru Xiao Chuan-Jen Hsu Jin-Wu Tsai Luk H. Vandenberghe Chen-Chi Wu Yen-Fu Cheng Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65 Molecular Therapy: Methods & Clinical Development in utero microinjection AAV2/Anc80L65 inner ears gene therapy hereditary deafness adeno-associated virus |
| author_facet |
Chin-Ju Hu Ying-Chang Lu Yi-Hsiu Tsai Haw-Yuan Cheng Hiroki Takeda Chun-Ying Huang Ru Xiao Chuan-Jen Hsu Jin-Wu Tsai Luk H. Vandenberghe Chen-Chi Wu Yen-Fu Cheng |
| author_sort |
Chin-Ju Hu |
| title |
Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65 |
| title_short |
Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65 |
| title_full |
Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65 |
| title_fullStr |
Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65 |
| title_full_unstemmed |
Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65 |
| title_sort |
efficient in utero gene transfer to the mammalian inner ears by the synthetic adeno-associated viral vector anc80l65 |
| publisher |
Elsevier |
| series |
Molecular Therapy: Methods & Clinical Development |
| issn |
2329-0501 |
| publishDate |
2020-09-01 |
| description |
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. |
| topic |
in utero microinjection AAV2/Anc80L65 inner ears gene therapy hereditary deafness adeno-associated virus |
| url |
http://www.sciencedirect.com/science/article/pii/S2329050120301431 |
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doaj-3d99ac29290f4535b5ffc081bedfe8912020-11-25T02:54:22ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012020-09-0118493500Efficient in Utero Gene Transfer to the Mammalian Inner Ears by the Synthetic Adeno-Associated Viral Vector Anc80L65Chin-Ju Hu0Ying-Chang Lu1Yi-Hsiu Tsai2Haw-Yuan Cheng3Hiroki Takeda4Chun-Ying Huang5Ru Xiao6Chuan-Jen Hsu7Jin-Wu Tsai8Luk H. Vandenberghe9Chen-Chi Wu10Yen-Fu Cheng11Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Corresponding author: Chin-Ju Hu, Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Corresponding author: Ying-Chang Lu, Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Corresponding author: Yi-Hsiu Tsai, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.Institute of Brain Science, National Yang-Ming University, Taipei, TaiwanDepartment of Otolaryngology-Head and Neck Surgery, Kumamoto University Graduate School of Medicine, Kumamoto City, JapanDepartment of Medical Research, Taipei Veterans General Hospital, Taipei, TaiwanGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear, Boston, MA, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USADepartment of Otolaryngology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, TaiwanInstitute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, TaiwanGrousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear, Boston, MA, USA; Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA, USADepartment of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital Biomedical Park Hospital, Hsinchu, TaiwanDepartment of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Otolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Corresponding author: Yen-Fu Cheng, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.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.http://www.sciencedirect.com/science/article/pii/S2329050120301431in utero microinjectionAAV2/Anc80L65inner earsgene therapyhereditary deafnessadeno-associated virus |