Therapies for Photoreceptor Degeneration

光感受器变性的治疗

基本信息

批准号：
7217268
负责人：
TIANSEN LI
金额：
$ 18.33万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-06-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7217268
关键词：
ARA9 protein Address Adopted Affect Alternative Splicing Anabolism Animal Model Behavior Biological Preservation Cell Death Cells Cilia Clinical Research Cyclic GMP Defect Disease Disease model Ectopic Expression Exhibits Future Gene Targeting Genes Genetic Guanosine Triphosphate Phosphohydrolases Human Inherited Investigation Knock-out Laboratories Leber&apos s amaurosis Length Link Literature Mediating Modeling Molecular Chaperones Monitor Mus Mutant Strains Mice Mutation Outcome Outcomes Research Patients Phenotype Photoreceptors Population Process Proteins Repetitive Sequence Replacement Therapy Research Personnel Retina Retinal Cone Retinal Degeneration Retinitis Pigmentosa Screening procedure Serotyping Simulate System Testing Therapeutic Treatment Efficacy Tropism Variant Vertebrate Photoreceptors Work adeno-associated viral vector base clinical application clinically significant design disease phenotype functional restoration gene replacement gene therapy in vivo knock-down loss of function mutation phosphoric diester hydrolase photoreceptor degeneration programs promoter prototype restoration therapeutic gene transcription termination

项目摘要

DESCRIPTION (provided by applicant): The major objective of this proposal is to investigate therapeutic approaches for inherited photoreceptor degeneration. Murine models with defined genetic defects simulating human photoreceptor degeneration will serve as the primary experimental system with which to study the efficacy of replacement gene therapies. The gene defects to be studied are selected based on greater clinical significance as they cause severe forms of the disease and/or affect a large proportion of patients with photoreceptor degeneration. These studies will seek direct evidence that the gene replacement therapy will halt photoreceptor cell death even after such a process has begun in the retina, and will allow regrowth of photoreceptor outer segments and restoration of photoreceptor function. Issues relating to the efficient targeting of rod and cone photoreceptors and proof of efficacy with human gene constructs will be addressed. The outcomes of this research should provide the critical information necessary for a transition from genetic studies in animal models to future clinical applications of replacement gene therapy in patients with photoreceptor degeneration.

描述（由申请人提供）：该提案的主要目的是研究遗传性光感受器变性的治疗方法。模拟人类光感受器变性的具有明确遗传缺陷的小鼠模型将作为研究替代基因疗法功效的主要实验系统。要研究的基因缺陷是根据更大的临床意义来选择的，因为它们会导致严重的疾病形式和/或影响大部分患有光感受器变性的患者。这些研究将寻求直接证据，证明基因替代疗法将阻止感光细胞死亡，即使这种过程已经在视网膜中开始，并且将允许感光器外节重新生长并恢复感光器功能。将解决与杆状和锥状光感受器的有效靶向以及人类基因构建体的功效证明相关的问题。这项研究的结果应该为从动物模型的遗传学研究过渡到光感受器变性患者替代基因治疗的未来临床应用所需的关键信息。