INTRODUCING STABLE INFERTILITY BY RNA INTERFERENCE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目前这项研究的总体目标是开发一种长期抑制大脑或卵巢中基因表达的系统，可以用来导致狗和猫的永久性不孕。这个应用程序是爱荷华大学(UI)和俄勒冈州国家灵长类研究中心(ONPRC)合作的成果。为了实现原始应用程序的目标，我们已经执行了几个实验。这些实验涉及使用生物淘洗策略来识别可以通过血流传递的多肽表位，特别是大鼠下丘脑或卵巢中传递RNAi的细胞。经过五轮生物淘洗，我们选择了一个特定于下丘脑、卵巢或两者的表位，因此可以用于下一阶段的研究：基于这些选择的表位重新定向AAV的病毒趋向性，将RNA干扰传递到这些特定的细胞群。

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. The overall goal of the present study is to develop a system for longlasting inhibition of gene expression in the brain or ovary that can be used to cause permanent infertility in dogs and cats. This application is a collaborative effort between the University of Iowa (UI) and the Oregon National Primate Research Center (ONPRC). We have performed several experiments aimed at achieving the objectives of the original application. These experiments involve the use of a bio-panning strategy to identify peptide epitopes that can be delivered via the blood stream and specifically home to cells in either the hypothalamus or the ovary of the rat to deliver RNAi. After five rounds of bio-panning, we selected an epitope that specifically home to the hypothalamus, ovary or both, and that can therefore be used for the next phase of the study: re-directing viral tropism of AAV based on these selected epitopes to deliver RNA interference to those particular cell populations.