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

Overview

Journal Mol Ther Methods Clin Dev

Publisher Cell Press

Date 2020 Aug 11

PMID 32775487

Citations 14

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 . 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.

Citing Articles

AAV-mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives.

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References

Miwa T, Minoda R, Ise M, Yamada T, Yumoto E . Mouse otocyst transuterine gene transfer restores hearing in mice with connexin 30 deletion-associated hearing loss. Mol Ther. 2013; 21(6):1142-50. PMC: 3677317. DOI: 10.1038/mt.2013.62. View

Kim M, Cho H, Bae S, Lee B, Oh S, Kwon T . Methionine Sulfoxide Reductase B3-Targeted In Utero Gene Therapy Rescues Hearing Function in a Mouse Model of Congenital Sensorineural Hearing Loss. Antioxid Redox Signal. 2015; 24(11):590-602. PMC: 4840920. DOI: 10.1089/ars.2015.6442. View

Shibata S, Ranum P, Moteki H, Pan B, Goodwin A, Goodman S . RNA Interference Prevents Autosomal-Dominant Hearing Loss. Am J Hum Genet. 2016; 98(6):1101-1113. PMC: 4908151. DOI: 10.1016/j.ajhg.2016.03.028. View

Stojanova Z, Kwan T, Segil N . Epigenetic regulation of Atoh1 guides hair cell development in the mammalian cochlea. Development. 2015; 142(20):3529-36. PMC: 4631768. DOI: 10.1242/dev.126763. View

Liu Y, Okada T, Sheykholeslami K, Shimazaki K, Nomoto T, Muramatsu S . Specific and efficient transduction of Cochlear inner hair cells with recombinant adeno-associated virus type 3 vector. Mol Ther. 2005; 12(4):725-33. DOI: 10.1016/j.ymthe.2005.03.021. View

Omichi R, Yoshimura H, Shibata S, Vandenberghe L, Smith R . Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae. Mol Ther Methods Clin Dev. 2020; 17:1167-1177. PMC: 7270144. DOI: 10.1016/j.omtm.2020.05.007. View

Lu Y, Wu C, Yang T, Lin Y, Yu I, Lin S . Differences in the pathogenicity of the p.H723R mutation of the common deafness-associated SLC26A4 gene in humans and mice. PLoS One. 2013; 8(6):e64906. PMC: 3670936. DOI: 10.1371/journal.pone.0064906. View

Stickrod G . In utero injection of rat fetuses. Physiol Behav. 1981; 27(3):557-8. DOI: 10.1016/0031-9384(81)90349-8. View

Emptoz A, Michel V, Lelli A, Akil O, de Monvel J, Lahlou G . Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G. Proc Natl Acad Sci U S A. 2017; 114(36):9695-9700. PMC: 5594693. DOI: 10.1073/pnas.1708894114. View

10.

Bedrosian J, Gratton M, Brigande J, Tang W, Landau J, Bennett J . In vivo delivery of recombinant viruses to the fetal murine cochlea: transduction characteristics and long-term effects on auditory function. Mol Ther. 2006; 14(3):328-35. PMC: 4108343. DOI: 10.1016/j.ymthe.2006.04.003. View

11.

Suzuki J, Hashimoto K, Xiao R, Vandenberghe L, Liberman M . Cochlear gene therapy with ancestral AAV in adult mice: complete transduction of inner hair cells without cochlear dysfunction. Sci Rep. 2017; 7:45524. PMC: 5377419. DOI: 10.1038/srep45524. View

12.

Tao Y, Huang M, Shu Y, Ruprecht A, Wang H, Tang Y . Delivery of Adeno-Associated Virus Vectors in Adult Mammalian Inner-Ear Cell Subtypes Without Auditory Dysfunction. Hum Gene Ther. 2017; 29(4):492-506. PMC: 5909114. DOI: 10.1089/hum.2017.120. View

13.

Nist-Lund C, Pan B, Patterson A, Asai Y, Chen T, Zhou W . Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders. Nat Commun. 2019; 10(1):236. PMC: 6342993. DOI: 10.1038/s41467-018-08264-w. View

14.

Zinn E, Pacouret S, Khaychuk V, Turunen H, Carvalho L, Andres-Mateos E . In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector. Cell Rep. 2015; 12(6):1056-68. PMC: 4536165. DOI: 10.1016/j.celrep.2015.07.019. View

15.

Tan F, Chu C, Qi J, Li W, You D, Li K . AAV-ie enables safe and efficient gene transfer to inner ear cells. Nat Commun. 2019; 10(1):3733. PMC: 6700137. DOI: 10.1038/s41467-019-11687-8. View

16.

Wake M, Tobin S, Cone-Wesson B, Dahl H, Gillam L, McCormick L . Slight/mild sensorineural hearing loss in children. Pediatrics. 2006; 118(5):1842-51. DOI: 10.1542/peds.2005-3168. View

17.

Wang L, Jiang H, Brigande J . Gene transfer to the developing mouse inner ear by in vivo electroporation. J Vis Exp. 2012; (64). PMC: 3476378. DOI: 10.3791/3653. View

18.

Merentie M, Lottonen-Raikaslehto L, Parviainen V, Huusko J, Pikkarainen S, Mendel M . Efficacy and safety of myocardial gene transfer of adenovirus, adeno-associated virus and lentivirus vectors in the mouse heart. Gene Ther. 2015; 23(3):296-305. DOI: 10.1038/gt.2015.114. View

19.

DeWeerdt S . Prenatal gene therapy offers the earliest possible cure. Nature. 2018; 564(7735):S6-S8. DOI: 10.1038/d41586-018-07643-z. View

20.

Kim M, Ryu N, Kim H, Kim Y, Lee B, Kwon T . Targeted Gene Delivery into the Mammalian Inner Ear Using Synthetic Serotypes of Adeno-Associated Virus Vectors. Mol Ther Methods Clin Dev. 2019; 13:197-204. PMC: 6374519. DOI: 10.1016/j.omtm.2019.01.002. View