I-Corps: Development of Bent DNA Molecules as Amplifying Sensors

这个i-Corps项目的更广泛的影响/商业潜力是开发传感器来研究DNA与离子和有机小分子的相互作用，以及筛选以DNA为靶标的分子作为潜在的药物。DNA是生命最基本的元素之一。DNA与无机盐和有机小分子的相互作用对于理解生命系统中各种基本的细胞过程，破译与DNA损伤和修复相关的疾病和癌症的机制，以及发现、设计和开发治疗各种疾病和癌症的抑制剂和药物具有重要意义。拟议的传感器技术旨在放大、检测和量化各种分子(例如，金属离子、有机小分子和DNA靶向药物)与DNA的相互作用。虽然已经开发了各种技术来研究DNA与其他分子之间的相互作用，但目前的技术存在着各种缺点，例如需要昂贵、复杂的设备，或者缺乏灵敏度。这项技术的发展可能会受益于几个市场领域，包括生命科学研究工具、分析实验室服务和制药行业。这个i-Corps项目基于基于弯曲DNA分子的纳米放大器/传感器的开发，用于放大、检测和量化DNA与其他分子的相互作用。目前测量和量化DNA相互作用的方法存在缺陷，需要更容易、更敏感和更经济的技术。这项拟议的技术利用了弓箭形状的弯曲DNA分子，这些分子在机械应力下对离子、有机小分子和DNA靶向药物分子的存在更加敏感。所提出的设计是基于自组装弯曲DNA放大器。最近的研究结果表明，弯曲DNA放大器能够放大和检测DNA与14种不同的无机盐和有机小分子之间的相互作用，其中包括一种抗癌药物。这项技术可能会使生命科学研究活动成为可能，或者是以前不可能或不容易进行的。潜在的应用可能包括开发一种分析方法，用于放大和检测DNA与各种分子和离子的相互作用，使人们能够定量地了解DNA与这些分子相互作用的机制，检测细胞和组织中重离子的积累，并将DNA靶向分子筛选为潜在的药物。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of sensors to investigate DNA interactions with ions and small organic molecules, and the screening of DNA-targeting molecules as potential drugs. DNA is one of the most essential elements of life. The interactions of DNA with inorganic salts and small organic molecules are important for understanding various fundamental cellular processes in living systems, for deciphering the mechanisms of diseases and cancers related to DNA damage and repair, and for discovering, designing, and developing inhibitors and drugs to treat various diseases and cancers. The proposed sensor technology is designed to amplify, detect, and quantify the interactions of various molecules (e.g., metal ions, small organic molecules, and DNA-targeting drugs) with DNA. Although various techniques have been developed for investigating the interactions between DNA and other molecules, the current techniques suffer from various drawbacks, such as requiring expensive, sophisticated, and complex equipment, or lacking sensitivity. The development of this technology may benefit and has application in several market areas including life science research tools, analytical lab services, and the pharmaceutical industry.This I-Corps project is based on the development of nano-amplifiers/sensors based on bent DNA molecules for amplifying, detecting, and quantifying DNA interactions with other molecules. Current methods to measure and quantify DNA interactions have drawbacks and there is a need for easier, more sensitive, and more economic technologies. The proposed technology makes use of bent DNA molecules in the shape of archery bows that are under mechanical stress and more sensitive to the presence of ions, small organic molecules, and DNA-targeting drug molecules. The proposed design is based on self-assembled bent DNA amplifiers. Recent results have demonstrated that bent DNA amplifiers are able to amplify and detect the interactions between DNA and 14 different inorganic salts and small organic molecules, including one anti-cancer drug. This technology may enable life science research activities that were previously not possible or easy to carry out. The potential applications may include developing an assay for amplifying and detecting DNA interactions with various molecules and ions, enabling quantitative understanding of the mechanisms of DNA interactions with these molecules, detecting the accumulation of heavy ions in cells and tissues, and screening DNA-targeting molecules as potential drugs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.