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中文摘要
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描述(由申请人提供):提出了一种通过直接对单个碱基进行电子测量来对单个DNA分子进行测序的新方法。该方法利用新发现的悬浮脂质双层构型中的蛋白质孔,简单的电子模型和计算表明,在测量孔阻断电流方面,该方法的灵敏度提高了10倍。第二个关键创新是将用于诱导离子电流通过孔道的方法与用于驱动DNA通过孔道的移位的方法分开,允许分别进行优化。在第一阶段,将调查与第二次创新有关的关键问题,并预测一个完整系统的性能。在第二阶段,将对将系统的所有要素组合成基本形式的初步实验室设备进行评估。该项目是电子生物科学有限责任公司(EBS)、新型悬浮膜结构的发明者Henry White教授和蛋白质孔DNA易位科学的先驱David Deamer教授的合作成果。建议的DNA直接电子测序方法可以实现对人类基因组的常规测序。从理论上讲,该系统将允许在不到一小时的时间内对30亿个碱基的哺乳动物基因组进行测序,比目前的系统提高了1000倍。这种快速、低成本的测序可以用来获得关于疾病易感性和治疗的个性化信息,从而可能使医学发生革命性的变化。
英文摘要
DESCRIPTION (provided by applicant): A new method is proposed for sequencing a single DNA molecule via direct electronic measurement of individual bases. The method utilizes a protein pore in a newly discovered suspended lipid bilayer configuration that simple electronic models and calculations show offers a factor of ten sensitivity improvement in measurement of the pore blocking current. A second key innovation is to separate the means used to induce the ionic current through the pore from the means used to drive DNA translocation through the pore, allowing each to be optimized separately. In Phase I the key questions relating to the second innovation will be investigated and the performance of a complete system projected. In Phase II, a preliminary laboratory apparatus that combines all elements of the system in a basic form will be evaluated. This program is a collaboration between Electronic Bio Sciences LLC (EBS), pioneers in the development of new ultra low noise electronic readout architectures for biology, the group of Professor Henry White, the inventors of the new suspended membrane configuration, and Professor David Deamer, a pioneer in the science of DNA translocation through protein pores. The proposed direct electronic sequencing of DNA method could allow the ability for routine sequencing of the human genome. In theory this system would allow a 3 billion base mammalian genome to be sequenced in under an hour, a 1000 times improvement over current systems. Such rapid low cost sequencing could be used to obtain individualized information on predisposition to diseases and treatments and could thereby revolutionize medicine.
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DOI: 10.1021/ja906951g
发表时间: 2010-02-17
期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子: 15
作者: [Lathrop, Daniel K., Ervin, Eric N., Barrall, Geoffrey A., Keehan, Michael G., Kawano, Ryuji, Krupka, Michael A., White, Henry S., Hibbs, Andrew H.]
通讯作者: Hibbs, Andrew H.
New Platform for Ionic Current Measurement with Application to DNA Sequencing
  • 批准号:
    7938987
  • 项目类别:
  • 资助金额:
    $19.81万
  • 财政年份:
    2009
  • 负责人:
    ANDREW D HIBBS
  • 依托单位:
Nanopatch System for Next Generation Ion Channel Recordings
  • 批准号:
    7272507
  • 项目类别:
  • 资助金额:
    $15.3万
  • 财政年份:
    2007
  • 负责人:
    ANDREW D HIBBS
  • 依托单位:
New Platform for Ionic Current Measurement with Application to DNA Sequencing
  • 批准号:
    7692710
  • 项目类别:
  • 资助金额:
    $37.34万
  • 财政年份:
    2007
  • 负责人:
    ANDREW D HIBBS
  • 依托单位:
New Method for Direct Electronic Sequencing of DNA
  • 批准号:
    7326669
  • 项目类别:
  • 资助金额:
    $21.05万
  • 财政年份:
    2007
  • 负责人:
    ANDREW D HIBBS
  • 依托单位:
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