Developing DNA-Based Molecular Robots

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SUMMARY The majority of medical diagnostic and therapeutic procedures depend on invasive methods and sophisticated tools. These medical practices are non-convenient for the patients, are expensive, are time- consuming, and require intensive use of equipment and professional resources. Therefore, there exists a critical need for medical devices and procedures that minimize the inconvenience, cost, and resource allocation. The PI's long-term goal is to develop intelligent molecular robots that detect diseases and treat them by providing appropriate responses that are timely, inexpensive, and convenient. PI's overall objectives for the proposed project are to construct a prototype of the envisioned robot, produce the preliminary data that will support submitting a targeted R01 grant at NIH, and establish a translational research program with support from his team. The PI's team will build a programmable DNA-based robot that aims at i) detecting specific RNA molecules and ii) generating amplified signals and select gene products. Leveraging PI's background, qualifications, and expertise that this proposal will advocate and the strong team he has assembled, he and his team are well-positioned to pursue this research. The proposed idea is likely to succeed because the PI's preliminary data demonstrates the project's feasibility. As a proof of concept, the team will design the robot to detect specific microRNA molecules that are known markers of breast cancer cells. The robot responds to the existence of the microRNAs by overexpressing the accompanying therapeutic gene. Modifying and altering domain properties of DNA-based molecular machines are inexpensive, fast, and efficient. Hence, the proposed work potentially has a broad reach – given the team can readily change the robot to enable detection of a host of biomolecules, including but not limited to various microRNAs. To achieve the goal of the proposed project, the PI will address the following three specific aims: • Aim 1: Design, construct, and characterize the robot's structural, optical, and functional properties, resulting in the construction of an efficient robot. • Aim 2: Develop target specificity and demonstrate the robot's diagnostic and therapeutic capabilities that enable both colorimetric detection and elimination of the target cancer cells. • Aim 3: Establish a vigorous translational research program and involve students in the research, provide mentorship and training for students to train the impactful workforce, scientists, and leaders of the future; in alignment with the mission of NIH. If successful, the proposed research will result in preliminary data that informs larger grant applications to develop molecular robots that perform diagnostic and therapeutics.