EMT/NANO: Autonomous Programmable DNA Devices Using DNAzymes

EMT/NANO：使用 DNAzyme 的自主可编程 DNA 设备

• 批准号: 0829797
• 负责人: John Reif
• 金额: $ 20万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0829797&HistoricalAwards=false
• 关键词: EMT; NANO; Autonomous; Programmable; DNA

Intellectual Merit: A major challenge in Nanoscience is the design of synthetic molecular devices that run autonomously (that is, without externally mediated changes per work-cycle) and are programmable (modifiable behavior without full redesign). DNA-based synthetic molecular devices have advantages of simplicity of design and engineering, due to predictable secondary structure and well-established biochemistry. Tasks: The main Task is optimized design and experimental demonstration of molecular devices composed of DNA strands and DNAzyme. with unique advantages of being autonomous and programmable, requiring no protein enzymes. The experiments will be executed in carefully stages of increasing complexity. First to be demonstrated is a limited ability computational device, termed a DNAzyme calculator. Next to be demonstrated is a finite state automata device, DNAzyme FSA, which executes finite state transitions using DNAzymes. Further demonstrations will be extensions to probabilistic automata and non-deterministic automata. The keystone demonstration is a DNAzyme doctor device giving transduction of nucleic acid expression: programmed to respond to under-expression or over-expression of certain nucleic acid strands that may indicate a disease, and providing a response release of appropriate strands that can act as a drug remedy. Secondary Tasks are computer software for optimized design/simulation using realistic stochastic models and correlated to laboratory tests. Broader Impact: The development of autonomous and programmable molecular devices has a vast number of critical applications in the assembly and control of molecular scale devices. Although this work will be limited to the test tube to demonstrate fundamental capabilities, the impact of a DNAzyme doctor operating in vivo could be enormous in medicine. Important educational impact of the proposed research includes the highly interdisciplinary training of graduate students and postdocs.

智力优势：纳米科学的一个主要挑战是设计自主运行的合成分子设备（即每个工作周期没有外部介导的变化）和可编程（无需完全重新设计即可修改行为）。基于dna的合成分子器件由于具有可预测的二级结构和完善的生物化学机制，具有设计简单、工程简单等优点。主要任务是DNA链和DNAzyme组成的分子器件的优化设计和实验演示。具有自主和可编程的独特优势，不需要蛋白质酶。这些实验将在日益复杂的过程中小心翼翼地进行。首先要演示的是一个功能有限的计算设备，称为DNAzyme计算器。接下来要演示的是&amp；#64257；状态自动机设备DNAzyme FSA，执行&amp；#64257；使用DNAzymes进行夜间状态转换。进一步的演示将扩展到概率自动机和非确定性自动机。关键的演示是一种DNAzyme医生装置，它提供核酸表达的转导：对可能指示疾病的某些核酸链的过表达或过表达作出反应，并提供可作为药物补救措施的适当链的反应释放。辅助任务是使用现实随机模型进行优化设计/模拟的计算机软件，并与实验室测试相关。更广泛的影响：自主和可编程分子器件的发展在分子尺度器件的组装和控制方面具有大量的关键应用。尽管这项工作将仅限于试管，以证明其基本能力，但DNAzyme医生在体内操作的影响可能是巨大的。该研究的重要教育影响包括对研究生和博士后的高度跨学科培训。