RETINOGEOGRAPHIC DISTRIBUTION OF SECRETED RETINOSCHISIN

分泌性视网膜分裂素的视网膜地理分布

基本信息

批准号：
8357820
负责人：
MARTHA NEURINGER
金额：
$ 3.63万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8357820
关键词：
Adolescence Adult Affect Animal Model Biodistribution Cells Clinical Trials Funding Gene Transduction Agent Genes Grant Human Inherited Mutation National Center for Research Resources Patients Photoreceptors Prevention Primates Principal Investigator Proteins Research Research Infrastructure Resources Retinal Retinal Degeneration Retinal Detachment Rodent Route School-Age Population Source United States National Institutes of Health Vision Visual Acuity Vitreous Hemorrhage X-Linked Retinoschisis XLRS1 protein cost infancy male nonhuman primate safety testing vector

Adolescence Adult Affect Animal Model Biodistribution Cells Clinical Trials Funding Gene Transduction Agent Genes Grant Human Inherited Mutation National Center for Research Resources Patients Photoreceptors Prevention Primates Principal Investigator Proteins Research Research Infrastructure Resources Retinal Retinal Degeneration Retinal Detachment Rodent Route School-Age Population Source United States National Institutes of Health Vision Visual Acuity Vitreous Hemorrhage X-Linked Retinoschisis XLRS1 protein cost infancy male nonhuman primate safety testing vector

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项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. X-linked retinoschisis (XLRS) is an inherited form of retinal degeneration affecting young males. It is caused by mutations in a gene (retinoschisin or RS1) that is required for normal retinal function. Patients present with poor vision in infancy or at school age. Visual acuity usually worsens during the teenage years and then stabilizes until complicated by vitreous hemorrhage or retinal detachment during adulthood. In a previous study in a rodent animal model of XLRS, treatment with an AAV-RS1 gene therapy vector resulted in progressive and long-term improvement in retinal function and prevention of retinal cell degeneration. This project is testing the safety and biodistribution of AAV-RS1 vector, injected either subretinally or intravitreally in nonhuman primates, as a critical final step prior to a planned human clinical trial of this potentially sight-saving new therapy. Results indicate that both routes of delivery transduced RS1 to photoreceptors and resulted in expression of the secreted retinoschisin protein.

该副本是利用资源的众多研究子项目之一由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持而且，副投影的主要研究员可能是其他来源提供的包括其他NIH来源。列出的总费用可能代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 X连锁视网膜（XLR）是影响年轻男性的视网膜变性的一种遗传形式。它是由正常视网膜功能所需的基因（视网膜感染或RS1）中的突变引起的。患者在婴儿期或学龄时表现不佳。视力通常在青少年时期会恶化，然后稳定，直到成年期在成年期因玻璃体出血或视网膜脱离而复杂。在先前在XLR啮齿动物模型中的研究中，使用AAV-RS1基因治疗载体的治疗导致视网膜功能和预防视网膜细胞变性的进行性和长期改善。该项目正在测试AAV-RS1载体的安全性和生物分布，在非人类灵长类动物中注射下或玻璃体内注射，这是在计划进行这种潜在的避免视力新疗法的人类临床试验之前的关键最后一步。结果表明，两种递送途径均将RS1转移至感光体，并导致分泌的视网膜感染蛋白的表达。