Xenotransplant and Genome Editing Core

异种移植和基因组编辑核心

• 批准号: 10673647
• 负责人: Daniel Starczynowski
• 金额: $ 18.27万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673647
• 关键词: Acceleration; Animal Model; Animals; Biological Assay; Cell Lineage; Cell Therapy; Cell Transplantation; Cell physiology; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Collection; Communities; Cost efficiency; Development; Disease; Drug Monitoring; Effectiveness; Engineering; Engraftment; Future; Gene Targeting; Gene Transfer; Generations; Genetic; Genome engineering; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Hematological Disease; Hematology; Hematopoietic; Hematopoietic stem cells; Human; Human Resources; IL3 Gene; Immunocompromised Host; Immunodeficient Mouse; Injections; Investigation; Laboratories; Modality; Modeling; Molecular; Molecular Analysis; Monitor; Mouse Strains; Mus; Myelogenous; Newborn Infant; Non-Malignant; Non-Neoplastic Hematologic and Lymphocytic Disorder; PTPRC gene; Phase; Population; Procedures; Productivity; Publications; Pump; Rag1 Mouse; Regulation; Research; Research Design; Research Personnel; Resources; Scientist; Security; Services; Standardization; Supervision; T-Lymphocyte; Technology; Therapeutic; Tissue Banks; Training; Transgenic Animals; Transgenic Mice; Transgenic Organisms; Transplantation; Vendor; Xenograft procedure; blastocyst; career; cell behavior; cost effective; cost effectiveness; cost efficient; cytokine; design; drug development; epigenetic profiling; gang; genome editing; implantation; improved; in vivo; innovation; irradiation; member; molecular hematology; mouse model; novel; novel therapeutics; pharmacologic; pre-clinical; preclinical study; stem cell engraftment; stem cells; success; transcriptomic profiling

Abstract Genetically modified and immunocompromised animals are the gold-standard models for investigating the molecular regulation of hematopoietic cells in the context of normal development and diseases, and for the development of novel stem cell-based therapeutic modalities for a wide variety of non-malignant hematological disorders. The future of hematology research also lies in our ability to examine hematopoietic cell function at single cell level and correlate single cell behavior with transcriptome and epigenetic profiling. The CCCEH Xenotransplant and Genome Editing Core (XGEC) is an established, productive and innovative core designed to provide specialized mouse strains, a wide variety of animal services for efficiency and standardization of cell transplantation assays, and transgenic animal services in a timely and cost effective fashion to members of the CCHSCC. The overarching hypothesis is that a centralized core service providing the myriad mouse needs of CCHSCC members will enhance the effectiveness, timeliness, cost-efficiency and overall impact of the scientific research and thereby accelerate the discovery and treatment of hematological diseases. XGEC provides specialized mouse strains in a cost effective manner compared with external vendors, including a collection of immunodeficient mouse strains (i.e., NSG, NSG-3GM3, NRG-SGM3, Rag-/-gc-/- /WvWv, and B6.BoyJ) utilized for xenotransplantation of human hematopoietic cells, for preclinical studies concerning gene transfer in humans and mouse hematopoietic stem cells, for human hematopoietic stem cell and single cell engraftment studies, and for quantitative (competitive) hematopoietic stem cell engraftment studies (Aim 1). The XGEC further provides specialized animal services allowing for population and single cell transplantation assays, including animal irradiation and cell transplantation services (Aim 2), and animal manipulation and monitoring services (Aim 3). In addition, the XGEC offers all services for the generation of transgenic and genetically–modified mouse lines (Aim 4). Since it began offering CRISPR-Cas services in March 2014, the core has already generated engineered animal models to CCHMC investigators and among Centers and within the wider research community. Lastly, XGEC provides technical support and facilitates research collaborations for comprehensive design and analysis of in vivo studies (Aim 5). These services will facilitate the sharing of expertise and promote interaction between investigators participating in the CCCEH, and will attract new core users in the future. Overall, the XGEC offers a unique combination of animal services and concentrated expertise performed by well-trained personnel under the supervision of Drs. Starczynowski and Huang in a cost effective and standardized way, thereby providing state-of-the-art investigation of non- malignant molecular hematology. These services will support the development of new therapeutic modalities (pharmacological and cell-based) and translational Phase I and II studies.

抽象的 转基因和免疫功能低下的动物是研究的金色标准模型 在正常发育和疾病的背景下，造血细胞的分子调节，对于 开发新型干细胞的治疗方式，以用于多种非机敏性血液学 疾病。血液学研究的未来也在于我们检查造血细胞功能的能力 单细胞水平并将单细胞行为与转录组和表观遗传分析相关联。 CCCEH 异种移植和基因组编辑核心（XGEC）是建立，富有成效和创新的核心 旨在提供专业的老鼠应变，各种动物服务以提高效率和 细胞移植测定和转基因动物服务的标准化及时有效 CCHSCC成员的时尚。总体假设是提供的集中核心服务提供 CCHSCC成员的无数鼠标需求将提高有效性，及时性，成本效益和 科学研究的总体影响，从而加速了血液学的发现和治疗 疾病。 与外部供应商相比 包括免疫缺陷小鼠菌株的集合（即NSG，NSG-3GM3，NRG-SGM3，RAG - / - GC - / - /wvwv和b6.boyj）用于临床前研究的人造血细胞的异种移植 人类和小鼠造血干细胞中有关的基因转移，人造血干细胞 和单细胞植入研究，以及用于定量（竞争性的）造血干细胞植入 研究（目标1）。 XGEC进一步提供专门的动物服务，允许人口和单细胞 移植测定，包括动物辐射和细胞移植服务（AIM 2）和动物 操纵和监视服务（AIM 3）。此外，XGEC提供了所有的服务 转基因和遗传修饰的小鼠系（AIM 4）。由于它开始在 2014年3月，核心已经为CCHMC调查人员以及 中心和更广泛的研究社区。最后，XGEC提供技术支持和促进 研究和分析体内研究的研究合作（AIM 5）。这些服务将 促进共享专业知识并促进参加CCCEH的调查人员之间的互动， 并将在将来吸引新的核心用户。总体而言，XGEC提供了动物服务的独特组合 并在DR的监督下由训练有素的人员进行的集中专业知识。 Starczynowski 并以一种经济有效和标准化的方式，从而提供了最先进的调查 恶性分子血液学。这些服务将支持开发新的治疗方式 （药理学和基于细胞的）以及翻译I期和II期研究。