Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human Disease

基因组编辑和记录中心:下一代基因组和表观基因组编辑方法的开发和应用,以推进人类疾病的研究和治疗

基本信息

项目摘要

CENTER FOR GENOME EDITING AND RECORDING: PROJECT SUMMARY Recent advances in DNA sequencing and bioinformatics have generated vast numbers of sequence variants associated with disease that, in principle, hold the keys to breakthroughs in preventive medicine and therapeutic intervention. However, realizing the promise of personalized medicine will require accurate manipulation of DNA sequences and gene expression as well as interrogation of the functional consequences of sequence variants at a scale and level of accuracy not currently possible. The Center for Genome Editing and Recording (CGER) will address these challenges by creating technologies to detect, alter and record the sequence and output of the genome in individual cells and tissues. The CGER will exploit the programmable DNA binding and nickase activity of CRISPR-Cas proteins as well as engineered zinc finger and TALE proteins to create a new generation of tools to precisely engineer the genome and epigenome. These platforms will enable high-precision engineering of both the nuclear and mitochondrial genomes as well as heritable silencing or activation of messenger RNAs, long noncoding RNA and a host of other regulatory elements such as enhancers and insulator regions. Critically, these alterations can be made without introducing double stranded breaks to DNA, thereby avoiding DNA toxicity and minimizing reliance on complex and difficult-to-control endogenous DNA repair pathways. Collectively, these technologies will usher in a new era of safer, high precision and multiplexed genome and epigenome editing. In addition, we will exploit these platforms to develop higher-level multichannel molecular recorders that will allow us to track and reconstruct the life history of cells in an in vivo setting. We will add the ability to follow cells in space and time as well as record the history of their past cellular states to the existing phylogenetic lineage tracing systems pioneered in the previous embodiment of this Center. The center will be led by a team that collectively has a remarkable track record of developing bold, impactful new tools to expand their precision, efficacy, safety and scope, and finally exploiting these new capabilities to develop novel strategies to explore fundamental biological and biomedical problems. Our multidisciplinary team has a rich history of working together, which has been greatly accelerated by the CEGS structure in a manner that would simply not be possible if each co-PI had been working on similar problems in isolation. Leveraging the capabilities of the Whitehead Institute, MIT, The Broad Institute, Harvard University, Harvard Medical School, The Lewis Sigler Institute for Integrative Genomics at Princeton and the Massachusetts General Hospital, we aim to create transformative capabilities and have access to state-of-the- art research facilities as well as resources for training, education and outreach that will attract diverse talent to the field of genomics research.
基因组编辑和记录中心:项目摘要 DNA测序和生物信息学的最新进展产生了大量的序列变体 原则上,这些疾病是预防医学突破的关键, 治疗干预然而,实现个性化医疗的承诺将需要准确的 操纵DNA序列和基因表达以及询问功能后果 以目前不可能的规模和准确度来分析序列变异。 基因组编辑和记录中心(CGER)将通过创建 检测、改变和记录单个细胞和组织中基因组序列和输出的技术。 CGER将利用CRISPR-Cas蛋白的可编程DNA结合和切口酶活性, 工程化的锌指和TALE蛋白质,以创造新一代的工具来精确地设计基因组 和表观基因组。这些平台将使核和线粒体的高精度工程成为可能。 基因组以及信使RNA、长链非编码RNA和一系列 其它调节元件如增强子和绝缘子区域。关键是,这些改变可以 而不向DNA引入双链断裂,从而避免DNA毒性并最小化对 复杂且难以控制的内源性DNA修复途径。总的来说,这些技术将带来 一个更安全、高精度和多重基因组和表观基因组编辑的新时代。 此外,我们将利用这些平台开发更高级别的多通道分子记录仪, 将使我们能够在体内环境中追踪和重建细胞的生命史。我们将添加跟踪功能 细胞在空间和时间,以及记录他们过去的细胞状态的历史,以现有的系统发育 谱系追踪系统是该中心之前实施例中首创的。 该中心将由一个团队领导,该团队在开发大胆, 有影响力的新工具,以扩大其精度,有效性,安全性和范围,并最终利用这些新的 开发新策略以探索基本生物学和生物医学问题的能力。我们 多学科团队有着丰富的合作历史,CEGS大大加速了这一进程 如果每个共同主要研究者都在研究类似的问题, 隔离利用怀特黑德研究所、麻省理工学院、布罗德研究所、哈佛大学的能力, 哈佛医学院、普林斯顿刘易斯西格勒综合基因组研究所和 马萨诸塞州总医院,我们的目标是创造变革能力,并获得国家的- 艺术研究设施以及培训,教育和推广资源,将吸引不同的人才, 基因组学研究领域。

项目成果

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Brittany S. Adamson其他文献

Brittany S. Adamson的其他文献

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{{ truncateString('Brittany S. Adamson', 18)}}的其他基金

Mapping the DNA damage response in human cells with high-resolution functional genomics
利用高分辨率功能基因组学绘制人类细胞中的 DNA 损伤反应图
  • 批准号:
    10655450
  • 财政年份:
    2020
  • 资助金额:
    $ 250万
  • 项目类别:
Mapping the DNA damage response in human cells with high-resolution functional genomics
利用高分辨率功能基因组学绘制人类细胞中的 DNA 损伤反应图
  • 批准号:
    10461118
  • 财政年份:
    2020
  • 资助金额:
    $ 250万
  • 项目类别:
Mapping the DNA damage response in human cells with high-resolution functional genomics
利用高分辨率功能基因组学绘制人类细胞中的 DNA 损伤反应图
  • 批准号:
    10029232
  • 财政年份:
    2020
  • 资助金额:
    $ 250万
  • 项目类别:
Mapping the DNA damage response in human cells with high-resolution functional genomics
利用高分辨率功能基因组学绘制人类细胞中的 DNA 损伤反应图
  • 批准号:
    10245257
  • 财政年份:
    2020
  • 资助金额:
    $ 250万
  • 项目类别:
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human Disease
基因组编辑和记录中心:下一代基因组和表观基因组编辑方法的开发和应用,以推进人类疾病的研究和治疗
  • 批准号:
    10676734
  • 财政年份:
    2017
  • 资助金额:
    $ 250万
  • 项目类别:

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