INTRODUCING STABLE INFERTILITY BY RNA INTERFERENCE

这个子项目是许多利用 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。 在过去的六个月里，我们进行了多项实验，旨在实现原始应用程序的目标。这些实验涉及使用生物淘选策略来鉴定可以通过血流递送并特异性地归巢到大鼠下丘脑或卵巢中的细胞以递送RNAi的肽表位。到目前为止，我们已经进行了三轮生物淘选，并从下丘脑和卵巢中回收了噬菌体克隆，现在可以进行额外的生物淘选，以最终选择特异性归巢下丘脑，卵巢或两者的候选物，因此可以用于下一阶段的研究：基于这些选择的表位重定向AAV的病毒向性以将RNA干扰递送至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. 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. 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). During the past six months 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. To date, we have performed three rounds of bio-panning and recovered phage clones from both the hypothalamus and the ovary that can now be subjected to additional rounds of bio-panning to finally select candidates 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.