Developing DNA-Based Molecular Robots

摘要 大多数医疗诊断和治疗程序依赖于侵入性方法和 复杂的工具。这些医疗实践对患者来说不方便，费用昂贵，耗时长- 消耗，并需要密集使用设备和专业资源。因此，存在一种 迫切需要医疗设备和程序，以最大限度地减少不便、成本和资源 分配。PI的长期目标是开发检测疾病和治疗疾病的智能分子机器人 通过提供及时、廉价和方便的适当响应来满足他们的需求。 PI提出的项目的总体目标是构建一个设想的机器人的原型，Products 将支持在NIH提交定向R01拨款的初步数据，并建立 在他的团队的支持下，他的研究计划。PI的团队将建造一个可编程的基于DNA的机器人 它的目的是i)检测特定的RNA分子和ii)产生放大的信号和选择基因 产品。利用本提案将倡导的PI的背景、资格和专业知识，以及 他组建了一支强大的团队，他和他的团队处于有利地位，可以从事这项研究。建议数 这个想法很可能成功，因为PI的初步数据证明了该项目的可行性。作为证据 当然，该团队将设计机器人来检测特定的microRNA分子，这些分子是已知的标记 乳腺癌细胞的数量。机器人通过过度表达microRNAs来响应microRNAs的存在 伴随治疗基因。DNA基分子结构域性质的修饰和改变 机器价格便宜、速度快、效率高。因此，拟议的工作可能具有广泛的影响- 考虑到团队可以很容易地改变机器人以实现对一系列生物分子的检测，包括但不是 仅限于各种microRNA。为实现拟议项目的目标，PI将处理以下事项 三个具体目标： ·目标1：设计、建造和表征机器人的结构、光学和功能特性， 从而构建出一种高效的机器人。 ·目标2：开发目标特异性并展示机器人的诊断和治疗能力 这使得比色检测和消除靶癌细胞成为可能。 ·目标3：建立强有力的翻译研究计划，让学生参与研究， 为学生提供指导和培训，以培养有影响力的劳动力、科学家和领导者 未来的；与国家卫生研究院的使命一致的。 如果成功，拟议的研究将产生初步数据，为更大规模的拨款申请提供信息 开发能够进行诊断和治疗的分子机器人。

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.