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

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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.