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
基本信息
- 批准号:8357819
- 负责人:
- 金额:$ 5.82万
- 依托单位:
- 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:
- 关键词:AddressAreaBehavioralBrainCell Culture TechniquesChronicCollaborationsDiseaseEquipmentFundingGene SilencingGrantHuman ResourcesHuntington DiseaseIowaMacaca mulattaMethodologyNational Center for Research ResourcesNeurologicOregonPrimatesPrincipal InvestigatorRNA InterferenceResearchResearch InfrastructureResourcesRodentRodent ModelSafetySourceSymptomsTestingTherapeuticTranslatingTranslationsUnited States National Institutes of HealthUniversitiesViral VectorWorkclinically relevantcostexperienceexpression vectornervous system disorderneuropathologynonhuman primateputamen
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.
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 the University of Iowa and the Oregon National Primate Research Center (ONPRC). University of Iowa has experience developing and testing RNAi therapeutics in rodents, while the ONPRC has expertise in stereotaxic delivery of viral vectors to the NHP brain. Also, the ONPRC has methodologies, equipment and personnel in place that 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. To date, we have shown efficacy of reducing HTT expression in the rhesus macaque putamen by 45%. This suppression of HTT is not associated with the manifestation of any behavioral abnormalities nor neuropathological changes in the putamen.
这个子项目是许多利用资源的研究子项目之一
由NIH/NCRR资助的中心拨款提供。子项目的主要支持
而子项目的主要调查员可能是由其他来源提供的,
包括其它NIH来源。 列出的子项目总成本可能
代表子项目使用的中心基础设施的估计数量,
而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。
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)。这项研究是由爱荷华州大学和俄勒冈州国家灵长类动物研究中心(ONPRC)合作进行的。爱荷华州大学在啮齿动物中开发和测试RNAi疗法方面具有经验,而ONPRC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具有适当的方法、设备和人员,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。到目前为止,我们已经显示出将恒河猴壳核中的HTT表达降低45%的功效。HTT的这种抑制与任何行为异常的表现或壳核中的神经病理学变化无关。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Sergio R Ojeda其他文献
Sergio R Ojeda的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Sergio R Ojeda', 18)}}的其他基金
Altering Energy Balance by Systemic Delivery of RNAi to the Neuroendocrine Brain
通过将 RNAi 系统性递送至神经内分泌脑来改变能量平衡
- 批准号:
8539523 - 财政年份:2012
- 资助金额:
$ 5.82万 - 项目类别:
Altering Energy Balance by Systemic Delivery of RNAi to the Neuroendocrine Brain
通过将 RNAi 系统性递送至神经内分泌脑来改变能量平衡
- 批准号:
8427058 - 财政年份:2012
- 资助金额:
$ 5.82万 - 项目类别:
NOVEL MECHANISMS UNDERLYING THE TRANSSYNAPTIC CONTROL OF LHRH RELEASE
LHRH 释放的跨突触控制的新机制
- 批准号:
8357725 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别:
NEUROENDOCRINOLOGY OF PUBERTY AND SEXUAL DEVELOPMENT
青春期和性发育的神经内分泌学
- 批准号:
8357881 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别:
MOLECULAR AND STRUCTURAL BASES OF HYPOTHALAMIC PUBERTY
下丘脑青春期的分子和结构基础
- 批准号:
8357754 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别:
INTRODUCING STABLE INFERTILITY BY RNA INTERFERENCE
通过 RNA 干扰引入稳定的不孕症
- 批准号:
8357818 - 财政年份:2011
- 资助金额:
$ 5.82万 - 项目类别:
相似国自然基金
层出镰刀菌氮代谢调控因子AreA 介导伏马菌素 FB1 生物合成的作用机理
- 批准号:2021JJ40433
- 批准年份:2021
- 资助金额:0.0 万元
- 项目类别:省市级项目
寄主诱导梢腐病菌AreA和CYP51基因沉默增强甘蔗抗病性机制解析
- 批准号:32001603
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
AREA国际经济模型的移植.改进和应用
- 批准号:18870435
- 批准年份:1988
- 资助金额:2.0 万元
- 项目类别:面上项目
相似海外基金
Task Representations in Ventral Tegmental Area Dopamine Neurons across Shifts in Behavioral Strategy and Reward Expectation
腹侧被盖区多巴胺神经元的任务表征跨越行为策略和奖励期望的转变
- 批准号:
10679825 - 财政年份:2023
- 资助金额:
$ 5.82万 - 项目类别:
Peer-Delivered, Behavioral Activation Intervention to Improve Polysubstance Use and Retention in Mobile Telemedicine OUD Treatment in an Underserved, Rural Area
同伴提供的行为激活干预可改善服务不足的农村地区移动远程医疗 OUD 治疗中多物质的使用和保留
- 批准号:
10578063 - 财政年份:2022
- 资助金额:
$ 5.82万 - 项目类别:
Neural circuit mechanisms underlying behavioral control through corticostriatal pathways in an area- and input-specific manner
通过皮质纹状体通路以区域和输入特定方式进行行为控制的神经回路机制
- 批准号:
18H02545 - 财政年份:2018
- 资助金额:
$ 5.82万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Role of the newly identified area in primate dorsomedial prefrontal conrtex in the integrative regulation of behavioral strategies.
新发现的灵长类动物背内侧前额叶皮质区域在行为策略综合调节中的作用。
- 批准号:
22500349 - 财政年份:2010
- 资助金额:
$ 5.82万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Validating Area-Level Behavioral Profiles for Cancer Disparities Research
验证癌症差异研究的区域级行为概况
- 批准号:
7455950 - 财政年份:2007
- 资助金额:
$ 5.82万 - 项目类别:
Validating Area-Level Behavioral Profiles for Cancer Disparities Research
验证癌症差异研究的区域级行为概况
- 批准号:
7305411 - 财政年份:2007
- 资助金额:
$ 5.82万 - 项目类别:
Doctoral Dissertation Improvement: Behavioral Ecology of Chimpanzees Living in a Dry Area, Ugalla, Tanzania
博士论文改进:生活在坦桑尼亚乌加拉干旱地区的黑猩猩的行为生态学
- 批准号:
0128157 - 财政年份:2002
- 资助金额:
$ 5.82万 - 项目类别:
Standard Grant
Dissertation Research: Quantifying Edge, Behavioral, and Climatic Effects on Survivorship Estimates of an Area-Sensitive Non-Migratory Sparrow
论文研究:量化边缘、行为和气候对区域敏感非迁徙麻雀生存估计的影响
- 批准号:
9902226 - 财政年份:1999
- 资助金额:
$ 5.82万 - 项目类别:
Standard Grant
Dissertation Research: Dynamics in Behavioral Adaptation to a Transportation Innovation: A Case Study of the Bay Area Rapid Transit District (BART)
论文研究:交通创新行为适应动态:湾区捷运区 (BART) 案例研究
- 批准号:
9712089 - 财政年份:1997
- 资助金额:
$ 5.82万 - 项目类别:
Standard Grant
CLINICAL STUDY CONCERNING WITH A ROLE OF THE SUPPLEMENTARY MOTOR AREA AND CINGULATE MOTOR AREA IN HUMAN BEHAVIORAL CONTROL
辅助运动区和扣带运动区在人类行为控制中作用的临床研究
- 批准号:
07670727 - 财政年份:1995
- 资助金额:
$ 5.82万 - 项目类别:
Grant-in-Aid for Scientific Research (C)