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A National iPS Cell Network with Deep Phenotyping for Translational Research

具有深度表型分析功能的国家 iPS 细胞网络，用于转化研究

基本信息

批准号：
9354528
负责人：
Chad Albert Cowan
金额：
$ 80.59万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9354528
关键词：
American Biology Blood specimen Catalogs Cell Culture Techniques Cell Line Cell Lineage Cell Therapy Cells Clinical Clone Cells Cohort Studies Collection Communities Consent Derivation procedure Development Differentiated Gene Disease Disease model Fluorochrome Framingham Heart Study Funding Mechanisms Future Generations Genes Genetic Genetic Polymorphism Genotype Goals Human Human Cell Line Human Cloning Human Genome In Vitro Individual Knock-in Laboratories Lung Maintenance Methodology Mission Mutation Participant Patients Phenotype Population Preclinical Drug Evaluation Protocols documentation Reagent Reporter Research Research Infrastructure Research Personnel Resources Sampling Scientist Site Source Techniques Technology Training Training Programs Training and Education Translational Research advanced disease base body system cell bank cohort design genetic manipulation genome editing human disease induced pluripotent stem cell open source personalized therapeutic programs regenerative repository therapeutic development tool web page

项目摘要

Project Summary/Abstract The discovery of iPSCs provides an unprecedented opportunity for any scientist to derive an inexhaustible supply of patient-derived primary cells. These cells containing each patient's own genetic background can now be applied for in vitro human disease modeling, drug screening of personalized therapeutics, and the development of future regenerative cell-based therapies. The most valuable human clones already generated by the CTSA investigators collaborating on this proposal not only carry common disease-associated mutations and polymorphisms, but also carry knock-in fluorochrome reporters targeted to specific loci through state-of-the-art gene editing technologies. The goal of this proposal is the establishment of a CTSA network of induced pluripotent stem cell (iPSC) repositories and iPSC cores that will enable advanced disease modeling using >1000 existing normal and disease specific human cell lines and banking 6,000 additional samples procured from the 2nd and 3rd generation participants of the Framingham Study. A concerted effort for curation, sharing, and distribution of this vital resource across all CTSAs does not exist. This proposal thus creates a CTSA iPSC Network led by teams who have championed an `Open Source Biology' approach, freely sharing iPSC lines and their reprogramming reagents with more than 500 labs to date across the globe. Its goals are to make patient-derived iPSCs together with the tools and expertise for their genetic manipulation available to the greater research community on a large scale to realize their promise for extending understanding of disease and developing potential therapies. To achieve these goals, it proposes: a) national sharing of >1000 iPSC lines already derived by the CTSA teams collaborating in this proposal, representing a critical resource in high demand by both basic and clinical researchers, b) development and support of formalized education and training programs able to nationally disseminate the expertise required to fully harness these new tools and differentiate them into the wide diversity of human cell lineages, c) maintenance and sharing of open source gene-editing tools and gene edited iPSC lines that will enable CTSA investigators to manipulate the human genome at will, and d) derivation for national sharing of additional iPSC lines generated from the most densely clinically and genetically phenotyped cohort of individuals currently followed in the USA today: the ~6,000 participants of the second and third generations of the Framingham Study.

项目概要/摘要 iPSC 的发现为任何科学家提供了前所未有的机会来自患者的原代细胞取之不尽、用之不竭。这些细胞含有每个患者自己的基因背景现可应用于体外人类疾病建模、个性化药物筛选疗法，以及未来基于再生细胞的疗法的发展。最有价值的人 CTSA 研究人员就该提案进行合作，已经生成的克隆不仅具有共同点与疾病相关的突变和多态性，还携带敲入荧光染料报告基因通过最先进的基因编辑技术针对特定位点。该提案的目标是建立诱导多能干细胞 (iPSC) 储存库 CTSA 网络 iPSC 核心将使用超过 1000 个现有正常和疾病进行高级疾病建模特定的人类细胞系并储存从第二和第三次采购的 6,000 个额外样本弗雷明汉研究的一代参与者。在所有 CTSA 中协调一致地管理、共享和分发这一重要资源并不意味着存在。因此，该提案创建了一个由倡导“开放”的团队领导的 CTSA iPSC 网络 Source Biology 的方法，与多家公司免费共享 iPSC 系及其重编程试剂迄今为止，全球已有 500 个实验室。其目标是与工具一起制造源自患者的 iPSC 以及大规模向更广泛的研究界提供其基因操作的专业知识实现他们扩展对疾病的了解和开发潜在疗法的承诺。到为了实现这些目标，它建议： a) 全国共享 CTSA 已经派生的 >1000 个 iPSC 系团队在此提案中进行合作，代表了基础和社区都高度需求的关键资源临床研究人员，b) 制定和支持正规教育和培训计划，能够在全国范围内传播充分利用这些新工具并将其区分为人类细胞谱系的广泛多样性，c）开源基因编辑工具的维护和共享以及基因编辑的 iPSC 细胞系，使 CTSA 研究人员能够随意操纵人类基因组， d) 推导国家共享从最密集的临床中产生的额外 iPSC 系目前在美国追踪的个体基因表型队列：约 6,000 弗雷明汉研究的第二代和第三代参与者。