Developing DNA-Based Molecular Robots

开发基于 DNA 的分子机器人

• 批准号: 10417272
• 负责人: Reza Zadegan
• 金额: $ 14.4万
• 依托单位: NORTH CAROLINA AGRI & TECH ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10417272
• 关键词: Address; Advocate; Applications Grants; Biological Markers; Biopsy; Breast Cancer Cell; Cellular biology; Chemotherapy and/or radiation; Collaborations; Communities; Consumption; Cost Allocation; DNA; DNA-Directed RNA Polymerase; Data; Detection; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Engineering; Equipment; Foundations; Future; Gene Expression; Genes; Genetic Transcription; Goals; Grant; Green Fluorescent Proteins; Image; Immunotherapy; In Vitro; Intelligence; Life; Link; Magnetic Resonance Imaging; Malignant Neoplasms; Medical; Medical Device; Medicine; Mentorship; Methods; MicroRNAs; Mission; Molecular; Molecular Biology; Molecular Machines; Monitor; Nanotechnology; Operative Surgical Procedures; Optics; Pathway interactions; Patients; Performance; Polymerase Chain Reaction; Positioning Attribute; Procedures; Production; Property; Protein Biosynthesis; Proteins; Public Health; RNA; Radiation therapy; Reaction Time; Research; Research Activity; Resource Allocation; Resources; Robot; Roentgen Rays; Scientist; Series; Signal Transduction; Specificity; Students; Testing; Therapeutic; Therapeutic Agents; Therapeutic procedure; Time; Training; Training Activity; Ultrasonography; United States National Institutes of Health; Work; X-Ray Computed Tomography; base; biophysical tools; cancer biomarkers; cancer cell; clinical diagnostics; design; design and construction; diagnostic platform; digital; disease diagnosis; feasibility research; gel electrophoresis; gene product; improved; interest; malignant breast neoplasm; overexpression; programs; prospective; prototype; reaction rate; repaired; response; student training; synthetic biology; theranostics; therapeutic gene; tool; translational research program

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.

概括 大多数医学诊断和治疗程序取决于侵入性方法， 软化工具。这些医学惯例对于患者而言是不偶然的，很昂贵，很及时 - 消费，需要大量使用设备和专业资源。因此，存在一个 对医疗设备和程序的关键需求，以最大程度地减少不便，成本和资源 分配。 PI的长期目标是开发智能分子机器人，以检测疾病并治疗 他们提供适当的响应，这些答复及时，便宜且方便。 PI对拟议项目的总体目标是构建设想机器人的原型，生产 将支持在NIH提交有针对性的R01赠款并建立翻译的初步数据 在他的团队的支持下进行研究计划。 PI的团队将建立一个可编程的基于DNA的机器人 旨在i）检测特定的RNA分子和II）产生放大信号并选择基因 产品。利用Pi的背景，资格和专业知识，该提议将倡导和 他和他的团队组成的强大团队非常适合进行这项研究。提议 想法很可能成功，因为PI的初步数据证明了项目的可行性。作为证明 概念，团队将设计机器人以检测已知标记的特定microRNA分子 乳腺癌细胞。机器人通过过表达MicroRNA的存在响应 参加治疗基因。基于DNA的分子的修改和改变域性能 机器便宜，快速且高效。因此，拟议的工作可能具有广泛的影响力 - 鉴于团队可以轻松更改机器人以启用一系列生物分子，包括但没有 限于各种microRNA。为了实现拟议项目的目标，PI将解决以下 三个具体目标： •目标1：设计，构造和表征机器人的结构，光学和功能特性， 导致建造有效的机器人。 •目标2：发展目标特异性并演示机器人的诊断和治疗能力 这使得能够比色检测和消除目标癌细胞。 •目标3：建立一个有力的翻译研究计划，让学生参与研究， 为学生提供训练和培训，以培训有影响力的员工，科学家和领导者 未来；与NIH的任务保持一致。 如果成功，拟议的研究将产生初步数据，以将较大的赠款申请告知 开发执行诊断和治疗剂的分子机器人。