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Instituting innovative CRISPR/Cas9 technology at an NCI Comprehensive Cancer Center transgenic facility

在 NCI 综合癌症中心转基因设施中采用创新的 CRISPR/Cas9 技术

基本信息

批准号：
10250365
负责人：
Jan Parker-Thornburg
金额：
$ 24.36万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-19 至 2022-08-31
项目状态：
已结题

项目摘要

Project Summary/Abstract Genetically engineered animal models are essential for understanding how genes can affect cancer susceptibility, development, and progression. For that reason, an animal model core service is essential for a Comprehensive Cancer Center (CCC). The Genetically Engineered Mouse Facility (GEMF) at MD Anderson Cancer Center was begun in 1988 by Dr. Guillermina Lozano to generate genetically modified animals in an effort to evaluate genes identified as possible tumor suppressors and activators. As many basic and translational research programs at MD Anderson are based on a genetic analyses of cancer, our research faculty must be able to access a strong transgenic facility. The GEMF provides a common source of state-of- the-art expertise and technical skills for Dr. Lozano and other MD Anderson investigators for the generation of their genetically engineered mouse models. Because of the individual nature of each mouse project, the GEMF provides comprehensive animal model services to all institutional investigators, regardless of prior expertise. The GEMF has provided services to more than 150 different Cancer Center members. Mouse models generated by the GEMF have been used in research reported in more than 160 publications. Dr. Jan Parker- Thornburg (this author, the co-Director of the GEMF at MD Anderson) provides essential individualized service including: 1) consultation on optimal animal models for an investigator's specific needs, 2) generation of the agreed-upon model, and 3) training in how to care for and evaluate the models produced. I bring in and test cutting-edge technologies for use by MD Anderson investigators. I am expected to develop new strategies and technologies to meet the needs of our faculty. Exciting new CRISPR/Cas9 technologies are currently being used, assessed, and refined in the GEMF. Work performed for on-site investigators (Richard Behringer, Gigi Lozano) has produced a number of insights into the technology, including describing the mosaic nature of the resulting F0 animals, and establishing new methods to increase the rate of exact targeting (homology-driven repair). Collaborations have been established to develop and test novel ways to generate conditional mutations. New Cas enzymes with different sequence specificity and those providing more faithful activity will be tested. Our results will be widely shared with other transgenic facilities as they are validated. We are highly involved with both developing and with standardizing new technologies for use at MD Anderson and in transgenic facilities worldwide.

项目总结/摘要基因工程动物模型对于理解基因如何影响癌症至关重要易感性、发育和进展。因此，动物模型核心服务对于综合癌症中心（CCC）。MD安德森的基因工程小鼠设施（GEMF）癌症中心于1988年由Guillermina Lozano博士开始，在一个努力评估被鉴定为可能的肿瘤抑制因子和激活因子的基因。许多基本的和 MD安德森的转化研究项目是基于癌症的遗传分析，我们的研究教师必须能够获得强大的转基因设施。GEMF提供了一个共同的来源， Lozano博士和其他MD安德森研究人员的最先进的专业知识和技术技能，他们的基因工程小鼠模型。由于每个鼠标项目的个别性质，GEMF 为所有机构研究者提供全面的动物模型服务，无论其先前的专业知识如何。 GEMF已为150多个不同的癌症中心成员提供服务。小鼠模型 GEMF产生的数据已被用于160多个出版物中报告的研究。简帕克医生- Thornburg（本文作者是MD安德森大学GEMF的联合主任）提供必要的个性化服务包括：1）为研究者的特定需求咨询最佳动物模型，2）生成商定的模型，以及3）培训如何照顾和评估所产生的模型。我带进来测试 MD安德森研究人员使用的尖端技术。我需要制定新的战略，技术，以满足我们教师的需求。令人兴奋的新CRISPR/Cas9技术目前正在在GEMF中使用、评估和完善。为现场研究者开展的工作（Richard Behringer、Gigi Lozano）对这项技术提出了许多见解，包括描述了产生的F0动物，并建立新的方法，以提高准确的靶向率（同源驱动修复）。已经建立了合作，以开发和测试新的方法来生成条件突变。具有不同序列特异性的新的Cas酶和提供更忠实活性的那些酶将被发现。得到考验我们的研究结果将被广泛分享与其他转基因设施，因为他们是有效的。我们高度参与开发和标准化在MD安德森和世界各地的转基因设施。