权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Gene Therapy for Treating Human Genetic Deafness Tested in Animal Models

治疗人类遗传性耳聋的基因疗法在动物模型中进行了测试

基本信息

批准号：
9217640
负责人：
XI LIN
金额：
$ 48.18万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-10 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9217640
关键词：
Adult Adverse effects Affect Animal Model Animals Auditory Brainstem Responses BIRC4 gene Basilar Membrane Biological Response Modifier Therapy Birth Cell Count Child Cochlea Cochlear duct Code Connexins DNA Sequence Alteration Data Development Feasibility Studies GJB2 gene GJB6 gene Gene Expression Genes Genetic Genetic Predisposition to Disease Genotype Green Fluorescent Proteins Hair Cells Hearing Histology Human Human Genetics Image In Vitro Inherited Injectable Injection of therapeutic agent Labyrinth Left Long-Term Effects Mediating Monitor Morphology Mus Mutation Noise-Induced Hearing Loss Patients Pattern Phenotype Plant Roots Prevalence Prevention Reporter Genes Reporting Research Route Safety Scala Tympani School-Age Population Sensorineural Hearing Loss Study models Testing Therapeutic Effect Time Toxic effect Transgenic Mice Translations Variant Viral Viral Proteins Viral Vector Virus Western Blotting Work age related clinical application congenital deafness critical period deafness design efficacy testing experimental study gene correction gene function gene replacement gene therapy hearing impairment in vivo mouse model null mutation otoacoustic emission overexpression postnatal pre-clinical preclinical study preclinical trial prevent protein E public health relevance ranpirnase response round window success transduction efficiency treatment effect

项目摘要

DESCRIPTION (provided by applicant): Genetic mutations are responsible for more than half of all congenital permanent hearing loss cases. The prevalence can be as high as 6 per 1,000 among school-age children. Mutations in the gap junction (GJ) proteins (e.g., GJB2) cause some of the most common forms of human congenital non-syndromic deafness. Genetic predisposition is also known to be an essential factor in age-dependent hearing loss (ADHL) and noise-induced hearing loss (NIHL), which affect tens of millions of patients. Today there is no biological treatment to correct the root cellular and genetic causes of inherited sensorineural hearing loss. Multiple research groups in the hearing field have worked for years to introduce gene therapy into clinical applications for the treatment of sensorineural deafness. Recent reports have yielded some promising results; however, the in vivo feasibility and reliability of virally mediated gene therapy in correcting the most common forms of non-syndromic human inherited deafness remain to be demonstrated. To date, gene therapy has not been successful at treating hearing loss in adult-stage mouse models. Moreover, none of the gene therapy studies for treating sensorineural hearing loss have advanced to the stage of systematic in vivo preclinical trials yet. The present project is the first to conduct major experiments required for n vivo preclinical studies of a gene therapy approach for treating the most common forms of non-syndromic deafness, as well as ADHL and NIHL, using mouse models. Studies will test the efficacy of gene therapy at both the postnatal and adult stages. We will study the feasibility and reliability of using a virally mediated gene replacement/augmentation therapy to prevent hearing loss in conditional Gjb2-/-, Gjb6-/-, and C57BL/6J (a popular mouse model for studying ADHL and NIHL) mice. We will also investigate the long-term efficacy and safety of the treatment in these mouse models. Carrying out the specific aims outlined here should fulfill some of the vital and necessary steps required for the translation of gene therapy into clinical applications.