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

描述（由申请人提供）：大鼠是研究人类疾病最常用的生理和药理学实验模型。通过在受精卵大鼠胚胎中进行基因转移或在胚胎干（ES）细胞中进行基因靶向的方法对大鼠进行遗传修饰的能力大大提高了大鼠在生物医学和制药研究中的能力。到目前为止，在大鼠身上产生靶向基因修饰需要手术移植胚胎。这种手术是成本和劳动密集型的，因为它需要麻醉（有潜在的并发症），雌性大鼠的术后护理（可能包括使用镇痛药），以及进行手术的人的技术专业知识。与此同时，动物研究界有一种强烈的愿望，即减少用于研究目的的动物的发病率、压力和痛苦。为了克服这些问题，我们提出了一种非手术胚胎移植（NSET）装置，可用于胚胎非手术移植到雌性大鼠体内。我们之前已经开发了一种用于小鼠的设备，该设备快速，不需要手术（包括相关的麻醉和术后护理），不需要什么专业知识，并且初步与转基因小鼠生产中的标准手术胚胎移植一样有效。虽然大鼠的生殖道解剖结构与小鼠有很大的不同，但我们相信我们可以成功地开发出大鼠的NSET装置原型。本提案的目的是设计大鼠NSET原型，制造原型装置，并证明装置在非手术胚胎移植中的功效。这些目标的成功将为寻求第二阶段奖励和NSET设备在学术和生物/制药研究机构的商业化提供基础。

DESCRIPTION (provided by applicant): Rats represent the most commonly used physiologically and pharmacological experimental model for studying human disease. The ability to genetically modify rats through methods of gene transfer in fertilized rat embryos or by gene targeting in embryonic stem (ES) cells has significantly increased the capabilities of rats in biomedical and pharmaceutical research. Until now, the production of targeted gene- modifications in rats requires the surgical transfer of embryos. This surgery is cost and labor intensive since it requires anesthesia (with potential complications), post-operative care of female rats (which may include the use of analgesics), as well as technical expertise on the part of the person carrying out the surgery. At the same time, there is a strong desire in the animal research community to reduce the morbidity, stress, and pain of animals used for research purposes. To overcome these problems we propose to develop a Non-Surgical Embryo Transfer (NSET) device that can be used for the non-surgical transfer of embryos into female rats. We have previously developed a device for use in mice that is rapid, does not require surgery (including the associated anesthesia and post-operative care), requires little expertise, and preliminarily is as efficacious as standard surgical embryo transfer in the production of transgenic mice. Although the rat reproductive tract anatomy is significantly different than that of mice, we believe we can successfully develop a rat NSET device prototype. The aims of this proposal are to design a rat NSET prototype, manufacture the prototype device, and demonstrate device efficacy for non-surgical transfer of embryos. Success in these aims will provide the foundation to seek a Phase II award and for the commercialization of the NSET device for academic and bio/pharma rat research facilities. PUBLIC HEALTH RELEVANCE: The development of a device for the non-surgical transfer of embryos into recipient female rats represents a substantial advance over existing methods for generating gene-modified rats by eliminating surgery, anesthesia, and post-operative care. The goal of this proposal is to develop, manufacture, and determine the efficacy of a non- surgical embryo transfer prototype device for the transfer of rat embryos.