INTRODUCING STABLE INFERTILITY BY RNA INTERFERENCE

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。次级项目的主要支助 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。 本研究的总体目标是开发一个长期的系统，持续抑制大脑或卵巢中的基因表达，可用于导致狗和猫的永久性不育。该应用程序是爱荷华州大学（UI）和俄勒冈州国家灵长类动物研究中心（ONPRC）之间的合作成果。 我们已经进行了旨在实现原始应用程序的目标的几个实验。这些实验涉及使用生物淘选策略来鉴定肽表位，所述肽表位可以通过血流递送并且特异性地归巢到大鼠的下丘脑或卵巢中的细胞以递送RNAi。在五轮生物淘选之后，我们选择了特异性地归巢于下丘脑、卵巢或两者的表位，并且因此可以用于研究的下一阶段：基于这些选择的表位重新定向AAV的病毒嗜性以将RNA干扰递送到那些特定的细胞群体。

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.