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

一种用于生产基因修饰大鼠的非手术胚胎移植装置

• 批准号: 7904469
• 负责人: Barbara Jean Stone
• 金额: $ 11.1万
• 依托单位: PARATECHS CORP.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2011-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904469
• 关键词: Analgesics; Anatomy; Anesthesia procedures; Animal Experimentation; Award; Caliber; Caring; Catheters; Communities; Derivation procedure; Development; Device or Instrument Development; Devices; Distress; Embryo; Embryo Transfer; Experimental Models; Female; Foundations; Gene Targeting; Gene Transfer; Gene-Modified; Goals; Grant; Imagery; Implant; Length; Medical; Methods; Modification; Morbidity - disease rate; Morphology; Mus; Operative Surgical Procedures; Pain; Performance; Persons; Pharmacologic Substance; Phase; Postoperative Period; Production; Rat Strains; Rattus; Research; Small Business Innovation Research Grant; Source; Stress; Technical Expertise; Techniques; Testing; Time; Transgenic Mice; Ultrasonography; United States National Institutes of Health; Work; animal pain; base; commercialization; cost; design; embryo culture; embryonic stem cell; flexibility; human disease; improved; innovation; prototype; public health relevance; reproductive; research facility; skills; stem; success; tool

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.

描述(申请人提供)：大鼠是研究人类疾病最常用的生理学和药理学实验模型。通过在受精大鼠胚胎中进行基因转移或在胚胎干细胞中进行基因打靶来对大鼠进行基因改造的能力大大提高了大鼠在生物医学和药物研究方面的能力。到目前为止，在大鼠身上产生有针对性的基因修饰需要通过手术移植胚胎。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)，手术后对雌性大鼠的护理(可能包括使用止痛剂)，以及进行手术的人的技术专长。与此同时，动物研究界强烈希望减少用于研究目的的动物的发病率、压力和疼痛。为了克服这些问题，我们建议开发一种非手术胚胎移植(NSET)装置，可以用于将胚胎非手术移植到雌性大鼠体内。我们之前已经开发出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)，几乎不需要专业知识，在生产转基因小鼠方面初步与标准的外科胚胎移植一样有效。虽然大鼠的生殖道解剖结构与小鼠的有很大不同，但我们相信我们可以成功地开发出大鼠NSET设备的原型。这项提议的目的是设计一个大鼠NSET原型，制造原型装置，并展示非手术胚胎移植装置的有效性。这些目标的成功将为寻求第二阶段奖励和将用于学术和生物/药用大鼠研究设施的NSET设备商业化奠定基础。 公共卫生相关性：将胚胎非手术移植到受体雌性大鼠体内的设备的开发，比现有的通过省去手术、麻醉和术后护理来产生转基因大鼠的方法有了实质性的进步。这项提议的目标是开发、制造并确定用于大鼠胚胎移植的非手术胚胎移植原型装置的有效性。