A non-surgical embryo transfer device for producing gene modified rats

 描述（由申请人提供）：ParaTechs Corporation开发用于生物医学研究的创新技术，同时寻求改善实验动物的动物福利。根据罗素和伯奇的动物研究3R准则，ParaTechs的主要目标之一是通过“减少、取代和改进”动物在研究中的使用，进一步推进动物伦理使用的指导原则。ParaTechs已经将一种用于小鼠的非手术胚胎移植装置（NSETTM）推向市场，该装置用一种非手术方法取代了手术胚胎移植，该方法已被证明对研究动物造成的压力较小。该项目的目标是开发一种用于大鼠非手术胚胎移植的设备和研究方案。该装置和方案对于胚胎移植是快速的、易于使用的、成本有效的和有效的。在第一阶段期间建立了该项目的原理验证，其中设计、制造和测试了大鼠NSET器械的多个原型。移植大鼠胚胎并获得存活的大鼠幼崽，证明了首次成功的大鼠非手术胚胎移植。第二阶段的目标是进一步确定 大鼠NSET技术并开发该设备以供生物医学研究界商业化。为实现这一目标，提出了四项目标。首先，我们将确定非手术胚胎移植相对于手术胚胎移植在Sprague-Dawley和Fischer 344大鼠中的桑椹胚和囊胚期胚胎的效率。这项研究将广泛应用于冷冻保存胚胎的移植和引入胚胎干细胞后转基因胚胎的移植。其次，我们将使用rNSET移植体外培养的胚胎，并将其效率与外科胚胎移植技术进行比较。这一目标将解决可能在发育早期被修改的大鼠胚胎的成功移植问题;例如，在为基因修改目的注射原核之后。第三，我们将测试使用大鼠NSET进行人工授精作为手术技术的替代方案。这一目标将支持使用该装置作为手术人工授精的替代方案，并作为体外受精的可能替代方案。第四，我们将评估与外科胚胎移植相比，NSET程序的压力降低水平。这些目标与ParaTechs的总体目标一致，即改善动物福利，并支持在生物医学研究中更有效和更人道地使用动物模型。

 DESCRIPTION (provided by applicant): ParaTechs Corporation develops innovative technologies for biomedical research while seeking to improve animal welfare for laboratory animals. One of ParaTechs' major goals is to further the guiding principles of ethical animal use by 'reducing, replacing and refining' the use of animals in research, according to the guidelines of Russell and Burch's 3Rs of animal research. ParaTechs already has brought to market a non-surgical embryo transfer device (NSETTM) for mice, which replaces surgical embryo transfers with a non-surgical method that has been proven to cause less stress in research animals. The goal of this project is to develop a device and a research protocol for nonsurgical embryo transfer in rats. The device and protocol is to be rapid, easy to use, cost effective, and efficien for embryo transfer. Poof of principle for the project was established during Phase I, where multiple prototypes of a rat NSET device were designed, manufactured, and tested. Rat embryos were transferred and viable rat pups were obtained, demonstrating the first successful nonsurgical embryo transfer in rats. The goal of Phase II is to further establish the parameters of rat NSET technology and to develop the device for commercialization to the biomedical research community. Four objectives are proposed to achieve this goal. First, we will determine the efficiency of non-surgical embryo transfer relative to surgical embryo transfer in Sprague-Dawley and Fischer 344 rats, for both morula and blastocyst stage embryos. This study will have broad applications for transfer of cryopreserved embryos and for transfer of genetically modified embryos after introduction of embryonic stem cells. Second, we will transfer in vitro cultured embryos using the rNSET and compared efficiency to surgical embryo transfer techniques. This aim will address successful transfer of rat embryos that may be modified very early in development; for example, after pronuclear injection for the purpose of genetic modification. Third, we will test the use of the rat NSET for artificial insemination as an alternative to surgical techniques. This aim will support the use of the device as an alternative t surgical artificial insemination and as a possible alternative to in vitro fertilization. Fourth, w will assess the level of stress reduction of the NSET procedure compared to surgical embryo transfer. These aims are consistent with ParaTechs' overall goal to improve animal welfare and support more effective and humane use of animal models in biomedical research.