基因治疗与遗传性耳聋
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摘要
超过60%的语前聋病例是由于遗传因素引起。遗传性耳聋患者的基因突变包括单核苷酸替换、碱基缺失、插入等,当这些突变导致耳聋基因的错义时便可临床上引起遗传性耳聋的症状。对这些突变在基因水平选择性纠正是目前遗传性耳聋生物治疗的新思路。CRISpR/Cas技术作为第三代的靶向基因组编辑技术系统,具有靶向、高效、易操作等优势,很大程度上推进了耳聋的基因治疗研究。本文对目前国内外耳聋的基因治疗研究现状进行回顾。
More than 60% of the Prelingual deafness cases are caused by genetic factors. Mutations in hereditary deafness include single nucleotide substitution, base deletion and insertion. These mutations lead to missense and nonsense mutations in the deafness gene. Selective correction at gene level is an innovative way to treat hereditary deafness.CRISPR/Cas technology has the advantages of targeting, high efficiency and easy operation as the third generation of targeted genome editing technology. It greatly promotes the research of gene therapy for hearing loss. In this paper, the current research status of gene therapy for hearing loss was reviewed.
More than 60% of the Prelingual deafness cases are caused by genetic factors. Mutations in hereditary deafness include single nucleotide substitution, base deletion and insertion. These mutations lead to missense and nonsense mutations in the deafness gene. Selective correction at gene level is an innovative way to treat hereditary deafness.CRISPR/Cas technology has the advantages of targeting, high efficiency and easy operation as the third generation of targeted genome editing technology. It greatly promotes the research of gene therapy for hearing loss. In this paper, the current research status of gene therapy for hearing loss was reviewed.
引文
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[33] Hansen tW,Cashore WJ,Oh W.Changes in piglet auditory brainstem response amplitudes without increases in serum or cerebrospinal fluid neuron-specific enolase[J].pediatr Res,1992,32(5):524-529.
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[35]Chen L,Guo W,Ren L,et al.A de novo silencer causes elimination of MItF-M expression and profound hearing loss in pigs[J].BMC Biol,2016,14:52-52.
[36]Guo W,Yi H,Yan Z,et al.the morphological and functional development of the stria vascularis in Miniature pigs[J].Reprod Fertil Dev,2017,29(3):585-593.
[37]Yi H,Guo W,Chen W,et al.Miniature pigs:a large animal model of cochlear implantation[J].Am J transl Res,2016,8(12):5494-5502.
[38]Yi HJ,Guo W,Wu N,et al.the temporal bone microdissection of miniature pigs as a useful large animal model for otologic research[J].Acta Otolaryngol,2014,134(1):26-33.
[39]Chen W,Yi H,Zhang L,et al.Establish the standard method of cochlear implant in Rongchang pig[J].Acta Otolaryngol,2017,137(5):503-510.
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[2]杨仕明.听觉损伤后毛细胞再生与聋病基因治疗策略[J].中华耳科学杂志,2009,7(4):271-277.
[3]Cai t,Seymour ML,Zhang H,et al.Conditional deletion of Atoh1 reveals distinct critical periods for survival and function of hair cells in the organ of Corti[J].Neurosci,2013,33(24):10110-10122.
[4]郭维维,胡吟燕,翟所强,等.腺病毒携带的LacZ基因在豚鼠耳蜗中的表达[J].听力学及言语疾病杂志,2001,9(1):36-37.
[5]杨仕明,杨伟炎,韩东一,等.聋病基因研究新策略-基因敲除鼠听功能和内耳形态的系统研究[J].中华耳科学杂志,2006,4(3):161-163.
[6]Chen W,Hu YY,Yang SM,et al.Adenoviral-mediated Hath1-EGFp gene transfer into guinea pig cochlear through an intact round window membrane in vivo[J].Journal of Otology,2008,3(1):18-23.
[7]陈伟,杨仕明,郭维维,等.腺病毒携带EGFp基因经完整圆窗膜转导豚鼠耳蜗的实验研究[J].中华耳科学杂志,2007,5(2):231-234.
[8]陈伟,郭维维,胡吟燕,等.Math1基因内耳导入后噪声性聋豚鼠听功能改变观察[J].中华耳科学杂志,2009,7(4):352-356.
[9]Chen W,Jongkamonwiwat N,Abbas L,et al.Restoration of auditory evoked responses by human ES-cell-derived otic progenitors[J].Nature,2012,490(7419):278-282.
[10]Ophir S,Neville ES,Ella H,et al.Genome-Scale CRISpR-Cas9 Knockout Screening in Human Cells[J].Science,2014,343(6166):84~87.
[11]Lander ES.the heroes of CRISpR[J].Cell,2016,164(1-2):18-28.
[12]Ishino Y,Shinagawa H,Makino K,et al.Nucleotide sequence of the iap gene,responsible for alkaline phosphatase isozyme conversion in Escherichia coli,and identification of the gene product[J].J Bacteriol,1987,169(12):5429-5433.
[13]Doudna JA,Charpentier E.the new frontier of genome engineering with CRISpR-Cas9[J].Science,2014,346(6213):1258096.
[14]Jinek M,Chylinski K,Fonfara I,et al.A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity[J].Science,2012,337(6096):816-821.
[15]Cong L,Ran FA,Cox D,et al.Multiplex genome engineering using CRISpR/Cas systems[J].Science,2013,339(6121):819-823.
[16]Jeggo pA.DNA breakage and repair[J].Adv Genet,1998,38(2):185-218.
[17]Gratz SJ,Cummings AM,Nguyen JN,et al.Genome engineering of Drosophila with the CRISpR RNA-guided Cas9 nuclease[J].Genetics,2013,194(4):1029-1035.
[18]Ran FA,Cong L,Yan WX,et al.In vivo genome editing using Staphylococcus aureus Cas9.Nature,2015,520(7546):186-191.
[19]王秋菊,纵亮.遗传性耳聋的基本概念(2)[J].听力学及言语疾病杂志,2016,24(1):110-112.
[20]Yan D,Liu XZ.Cochlear molecules and hereditary deafness[J].Front Biosci,2008,13(28):4972-4983.
[21]Harms DW,Quadros RM,Seruggia D,et al.Mouse Genome Editing Using the CRISpR/Cas System[J].Curr protoc Hum Genet,2014,83(53):15.7.1-15.7.27.
[22]Sloan-Heggen CM,Bierer AO,Shearer AE,et al.Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss[J].Hum Genet,2016,135(4):441-450.
[23]Akil O,Seal Rp,Burke K,et al.Restoration of hearing in the VGLUt3 knockout mouse using virally mediated gene therapy[J].Neuron,2012,75(2):283-293.
[24]Iizuka t,Kamiya K,Gotoh S,et al.perinatal Gjb2 gene transfer rescues hearing in amousemodel of hereditary deafness[J].Hum Mol Genet,2015,24(13):3651-3661.
[25]Chien WW,Isgrig K,Roy S,et al.Gene therapy restores hair cell stereocilia morphology in inner ears of deaf whirler mice[J].Mol ther,2016,24(1):17-25.
[26]pan B,Askew C,Galvin A,et al.Gene therapy restores auditory and vestibular function 1 in a mouse model of Usher syndrome,type 1c[J].Nat Biotechnol,2017,35(3):264-272.
[27]Xue Gao,Yong tao,Veronica Lamas,et al.treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents[J].Nature,2018,553(7687):217-221.
[28]Mandal pK,Ferreira LM,Collins R,et al.Efficient ablation of genes in human hematopoietic stem and effector cells using CRISp R/Cas9[J].Cell stem cell,2014,155,643-652.
[29]Harris Jp,Ryan AF.Fundamental immune mechanisms of the brain and inner ear[J].Otolaryngol Head Neck Surg,1995,112(6):639-653.
[30]Rivera t,Sanz L,Camarero G,et al.Drug delivery to the inner ear:strategies and their therapeutic implications for sensor ineural hearing loss[J].Curr Drug Deliv,2012,9(3):231-242.
[31]Chien WW,McDougald DS,Roy S,et al.Cochlear gene transfer mediated by adeno-associated virus:comparison of two surgical approaches[J].Laryngosco pe,2015,125(11):2557-2564.
[32]Suzuki J,Hashimoto K,Xiao R,et al.Cochlear gene therapy with ancestral AAV in adult mice:complete transduction of inner hair cells without cochlear dysfunction[J].Sci Rep,2017,(7):45524.
[33] Hansen tW,Cashore WJ,Oh W.Changes in piglet auditory brainstem response amplitudes without increases in serum or cerebrospinal fluid neuron-specific enolase[J].pediatr Res,1992,32(5):524-529.
[34]Guo WW,Yi HJ,Ren LL,et al.the morphology and electrophysiology of the cochlea of the miniature pig[J].Anat.Rec,2015,298(3),494e500.
[35]Chen L,Guo W,Ren L,et al.A de novo silencer causes elimination of MItF-M expression and profound hearing loss in pigs[J].BMC Biol,2016,14:52-52.
[36]Guo W,Yi H,Yan Z,et al.the morphological and functional development of the stria vascularis in Miniature pigs[J].Reprod Fertil Dev,2017,29(3):585-593.
[37]Yi H,Guo W,Chen W,et al.Miniature pigs:a large animal model of cochlear implantation[J].Am J transl Res,2016,8(12):5494-5502.
[38]Yi HJ,Guo W,Wu N,et al.the temporal bone microdissection of miniature pigs as a useful large animal model for otologic research[J].Acta Otolaryngol,2014,134(1):26-33.
[39]Chen W,Yi H,Zhang L,et al.Establish the standard method of cochlear implant in Rongchang pig[J].Acta Otolaryngol,2017,137(5):503-510.
[40]Ginn SL1,Alexander IE,Edelstein ML,et al.Gene therapy clinical trials worldwide to 2012-an update[J].J Gene Med,2013,15(2):65-77.