Exploration of Diverse Mobile Genetic Elements for Precision Genome Manipulation

探索用于精确基因组操作的多种移动遗传元件

基本信息

  • 批准号:
    9345109
  • 负责人:
  • 金额:
    $ 124.6万
  • 依托单位:
  • 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:
    2017-09-30 至 2022-07-31
  • 项目状态:
    已结题

项目摘要

The past five years have seen extraordinary advances in genome engineering technologies, yet we still lack efficient, robust tools for precise genome manipulation, particularly the ability to insert a desired sequence at a target site. Such tools would revolutionize our approach to treating human diseases and significantly increase the pace of functional genetic studies throughout the biological sciences. Current approaches are focused on the development of nucleases, such as TALENs, zinc-fingers, and Cas proteins, but there is a limit to the utility of these enzymes and they all rely on the host endogenous DNA repair machinery. Moreover, the use of a nuclease to achieve therapeutic gene editing requires additional efforts to safeguard against off-target mutagenic events. A partial solution to this challenge already exists in the form of mobile genetic elements (MGEs), systems that microbes have been using (or fighting) for millennia to achieve precise genome manipulation. We will explore the diverse pool of MGEs and identify those with characteristics that can be leveraged for eukaryotic genome editing. Precision genome manipulation can be broadly divided into three subcategories: insertions, deletions, and rearrangements, each of which forms the foundation for an array of applications. Our approach will be to consider each of these modes of operation separately to first select candidate MGEs or components of these systems through bioinformatics analysis and extrapolating from known systems. For example, transposases and recombinases may be harnessed for insertions, whereas the RNA-templated genome unscrambling that occurs in the ciliates may be suitable for adaptation for genome rearrangements. Once candidates for these three modes have been identified, we will functionally characterize them in vitro and then develop them for genome editing. Finally, we will assess the specificity, efficacy, and safety of these novel precision genome editors in vivo. This approach represents an innovative new direction in the development of genome engineering technology that overcomes the reliance on nucleases by designing new, self-contained enzymatic tools that can accomplish all three operational modes of genome manipulation. This work will complement our on-going research efforts to develop effective delivery methods for genome engineering components. Together, these technologies will allow us to realize the full potential of genome engineering, particularly as an avenue for treatment of human diseases.
在过去的五年里,基因工程技术取得了非凡的进步,但我们仍然缺乏

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(5)

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Feng Zhang其他文献

Feng Zhang的其他文献

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{{ truncateString('Feng Zhang', 18)}}的其他基金

Advancing programmable RNA-targeting tools for research and therapeutics
推进用于研究和治疗的可编程 RNA 靶向工具
  • 批准号:
    10475182
  • 财政年份:
    2017
  • 资助金额:
    $ 124.6万
  • 项目类别:
Exploration of Diverse Mobile Genetic Elements for Precision Genome Manipulation
探索用于精确基因组操作的多种移动遗传元件
  • 批准号:
    10251156
  • 财政年份:
    2017
  • 资助金额:
    $ 124.6万
  • 项目类别:
Advancing programmable RNA-targeting tools for research and therapeutics
推进用于研究和治疗的可编程 RNA 靶向工具
  • 批准号:
    10661786
  • 财政年份:
    2017
  • 资助金额:
    $ 124.6万
  • 项目类别:
Advancing programmable RNA-targeting tools for research and therapeutics
推进用于研究和治疗的可编程 RNA 靶向工具
  • 批准号:
    10273820
  • 财政年份:
    2017
  • 资助金额:
    $ 124.6万
  • 项目类别:
Programmable RNA-targeting tools
可编程 RNA 靶向工具
  • 批准号:
    9379750
  • 财政年份:
    2017
  • 资助金额:
    $ 124.6万
  • 项目类别:
DNA microscopy for spatially resolved genomic analyses in intact tissue
DNA 显微镜用于完整组织的空间分辨基因组分析
  • 批准号:
    9756434
  • 财政年份:
    2016
  • 资助金额:
    $ 124.6万
  • 项目类别:
LOCATER: Large-scale Observation of Cellular Activity Through Exosomal Reporters
LOCATER:通过外泌体记者大规模观察细胞活动
  • 批准号:
    9150623
  • 财政年份:
    2015
  • 资助金额:
    $ 124.6万
  • 项目类别:
Massively-parallel functional interrogation of psychiatric genetics
精神遗传学的大规模并行功能询问
  • 批准号:
    9310141
  • 财政年份:
    2015
  • 资助金额:
    $ 124.6万
  • 项目类别:
A novel mechanism of neurovascular protection in ischemic tolerance
缺血耐受中神经血管保护的新机制
  • 批准号:
    8940874
  • 财政年份:
    2015
  • 资助金额:
    $ 124.6万
  • 项目类别:
A novel mechanism of neurovascular protection in ischemic tolerance
缺血耐受中神经血管保护的新机制
  • 批准号:
    9234076
  • 财政年份:
    2015
  • 资助金额:
    $ 124.6万
  • 项目类别:

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