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: 8833473
• 负责人: Barbara Jean Stone
• 金额: $ 44.79万
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833473
• 关键词: Address; Adopted; Animal Experimentation; Animal Model; Animal Welfare; Animals; Artificial Insemination; Assisted Reproductive Techniques; Award; Behavior; Biological Markers; Biomedical Research; Birth; Businesses; Cardiovascular Diseases; Categories; Cell Culture Techniques; Collaborations; Communities; Data; Development; Device Designs; Devices; Distress; Embryo; Embryo Transfer; Ethics; Female; Fertilization in Vitro; Funding; Gene-Modified; Genetic; Goals; Guidelines; Implant; In Vitro; Individual; Injection of therapeutic agent; Institution; Knock-out; Laboratories; Laboratory Animals; Laboratory Rat; Laboratory Research; Lead; Letters; Life; Maintenance; Marketing; Measures; Methods; Modeling; Modification; Morals; Morula; Mus; Operative Surgical Procedures; Outcome; Pain; Painless; Pharmaceutical Preparations; Phase; Physiology; Procedures; Protocols documentation; Rat Strains; Rattus; Relative (related person); Research; Research Personnel; Resources; Rivers; Services; Societies; Staging; Stress; Techniques; Technology; Testing; Tissue Sample; Toxicology; Transgenic Organisms; blastocyst; commercialization; cost; cost effective; design; embryo culture; embryonic stem cell; genetic manipulation; human disease; human tissue; improved; innovative technologies; meetings; method development; mouse model; prototype; public health relevance; pup; sperm cell; tissue culture

 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.

 描述（由申请人提供）：ParaTechs Corporation 开发生物医学研究创新技术，同时寻求改善实验动物的动物福利，ParaTechs 的主要目标之一是通过“减少、替代和改进”动物使用伦理的指导原则。根据 Russell 和 Burch 的 3R 动物研究指南，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。用非手术方法代替手术胚胎移植，该方法已被证明可以减轻研究动物的压力。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。该项目在第一阶段建立了快速、易于使用、成本效益高且高效的原则，设计、制造了多个大鼠 NSET 装置原型并进行了大鼠胚胎移植和存活大鼠测试。小狗是获得，证明了大鼠中首次成功的非手术胚胎移植。第二阶段的目标是进一步建立参数。 大鼠 NSET 技术并开发用于生物医学研究界的商业化设备，以实现这一目标。首先，我们将确定 Sprague-Dawley 和 Fischer 中非手术胚胎移植相对于手术胚胎移植的效率。大鼠，对于桑椹胚期和胚泡期胚胎，这项研究将在冷冻保存胚胎的移植和引入胚胎干细胞后的转基因胚胎的移植方面具有广泛的应用。使用 rNSET 进行体外培养胚胎，并与外科胚胎移植技术进行效率比较，该目标将解决可能在发育早期进行修饰的大鼠胚胎的成功移植；第三，我们将进行原核注射。测试使用大鼠 NSET 进行人工授精作为手术技术的替代方法。这一目标将支持使用该装置作为手术人工授精的替代方法，并作为体外受精的可能替代方法。第四，我们将评估其水平。压力的与外科胚胎移植相比，减少 NSET 程序的数量与 ParaTechs 改善动物福利并支持在生物医学研究中更有效和人道地使用动物模型的总体目标是一致的。