RNA INTERFERENCE THERAPY FOR HUNTINGTON'S DISEASE: STUDIES IN NON-HUMAN PRIMATES

亨廷顿病的 RNA 干扰疗法：在非人类灵长类动物中的研究

• 批准号: 8173312
• 负责人: Sergio R Ojeda
• 金额: $ 7.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173312
• 关键词: Address; Area; Brain; Cell Culture Techniques; Chronic; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Disease; Equipment; Funding; Gene Silencing; Grant; Human Resources; Huntington Disease; Institution; Iowa; Laboratories; Methodology; Neurologic; Oregon; Primates; RNA Interference; Research; Research Personnel; Resources; Rodent; Rodent Model; Safety; Source; Symptoms; Testing; Therapeutic; Translating; Translations; United States National Institutes of Health; Universities; Viral Vector; Work; clinically relevant; experience; expression vector; nervous system disorder; neuropathology; nonhuman primate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This application addresses broad Challenge Area (15): 15-NS-102: Translation of Gene Silencing Therapeutics. The proposed challenge set forth in the RFA is to extend the current understanding of the feasibility and safety of RNA interference (RNAi) therapeutics for the treatment of chronic neurological disorders from rodent models of disease to a more clinically relevant species. The current proposal outlines a systematic approach to translate work we, and others, have undertaken to investigate RNAi as a potential therapy for the neurological disorder, Huntington's disease (HD) in cell culture and rodent models and apply these findings to the non-human primate (NHP). The proposed studies are a collaboration between two laboratories: the Davidson Laboratory at the University of Iowa and the Ojeda Laboratory at the Oregon National Primate Research Center (ONPRC). The Davidson Laboratory has experience developing and testing RNAi therapeutics in rodents, while the Ojeda Laboratory has expertise in stereotaxic delivery of viral vectors to the NHP brain. Also, the ONPRC has methodologies, equipment and personnel in place that, along with Dr. Ojeda's group, can evaluate if application of HTT suppression, or RNAi in general, induces neuropathology or neurological symptoms after delivery of RNAi expression vectors to NHP brain.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本申请涉及广泛的挑战领域（15）：15-NS-102：基因沉默治疗的翻译。 RFA中提出的挑战是将目前对RNA干扰（RNAi）疗法治疗慢性神经系统疾病的可行性和安全性的理解从啮齿动物疾病模型扩展到临床相关性更高的物种。目前的提案概述了一种系统的方法来翻译我们和其他人已经进行的研究RNAi作为神经系统疾病，亨廷顿病（HD）在细胞培养和啮齿动物模型中的潜在疗法的工作，并将这些发现应用于非人类灵长类动物（NHP）。拟议中的研究是两个实验室之间的合作：爱荷华州大学的戴维森实验室和俄勒冈州国家灵长类动物研究中心（ONPRC）的奥赫达实验室。Davidson实验室在啮齿动物中开发和测试RNAi疗法方面具有经验，而Ojeda实验室在将病毒载体立体定向递送到NHP大脑方面具有专业知识。此外，ONPRC拥有适当的方法、设备和人员，沿着Ojeda博士的小组，可以评估在将RNAi表达载体递送到NHP脑后，HTT抑制或一般RNAi的应用是否诱导神经病理学或神经症状。