title: The application of genome editing in studying hearing loss.
abstract: Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as one of the most powerful tools to study gene functions, and with potential to treat genetic disorders. Hearing loss is one of the most common sensory disorders, affecting approximately 1 in 500 newborns with no treatment. Mutations of inner ear genes contribute to the largest portion of genetic deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in human cells and model organisms such as zebrafish, mice and primates make it a promising technology in hearing research. With CRISPR/Cas9 technology, functions of inner ear genes can be studied efficiently by the disruption of normal gene alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed-repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo. Thus, application of CRISPR/Cas9 in hearing research will open up new avenues for understanding the pathology of genetic hearing loss and provide new routes in the development of treatment to restore hearing. In this review, we describe major methodologies currently used for genome editing. We will highlight applications of these technologies in studies of genetic disorders and discuss issues pertaining to applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing loss.
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Zou
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mittal
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: M'hamed
authors.initials: M
authors.lastname: Grati
authors.affiliation: Department of Biology, University of Miami, Miami, FL 33146, USA.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA; Department of Otology and Skull Base Surgery, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yilai
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA; Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Youg
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors.forename: Dinghua
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA. Electronic address: zheng-yi_chen@meei.harvard.edu.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital Central South University, Changsha, Hunan, China; Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China. Electronic address: xliu@med.miami.edu.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D064130:CRISPR-Associated Proteins / Q000235:genetics / Q000378:metabolism; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D018390:Gene Targeting; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000379:methods; D006309:Hearing / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D010641:Phenotype
chemical_list: D064130:CRISPR-Associated Proteins; D005819:Genetic Markers