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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本申请涉及广泛的挑战领域(15)：15-NS-102：基因沉默疗法的翻译。RFA中提出的挑战是将目前对RNA干扰(RNAi)疗法用于治疗慢性神经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更具临床相关性的物种。目前的提案概述了一种系统的方法来翻译我们和其他人致力于研究RNAi作为一种潜在的治疗神经疾病、细胞培养中的亨廷顿病(HD)和啮齿动物模型的工作，并将这些发现应用于非人类灵长类动物(NHP)。拟议的研究是两个实验室之间的合作：爱荷华大学的戴维森实验室和俄勒冈州国家灵长类研究中心(ONPRC)的Ojeda实验室。Davidson实验室有在啮齿动物身上开发和测试RNAi疗法的经验，而Ojeda实验室在通过立体定向将病毒载体输送到NHP大脑方面拥有专业知识。此外，ONPRC拥有方法学、设备和人员，与Ojeda博士的团队一起，可以评估在将RNAi表达载体输送到NHP大脑后，应用HTT抑制或RNAi是否会导致神经病理或神经症状。

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.