EMT/NANO: Autonomous Programmable DNA Devices Using DNAzymes

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中介的变化)和可编程的(无需完全重新设计即可修改行为)。基于DNA的合成分子装置具有设计和工程简单的优点，因为它具有可预测的二级结构和成熟的生物化学。任务：主要任务是DNA链和DNA酶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阶段谨慎地进行。首先要展示的是一种有限能力的计算设备，称为DNAzyme计算器。接下来要演示的是Nite状态自动机设备DNAzyme FSA，它使用DNAzyme执行Nite状态转换。进一步的演示将是概率自动机和非确定性自动机的扩展。Keystone演示是一种DNAzyme医生设备，提供核酸表达的转导：编程为对可能指示疾病的某些核酸链的表达不足或过度表达做出反应，并提供可作为药物药物的适当链的反应性释放。次要任务是计算机软件，用于使用真实的随机模型进行优化设计/模拟，并与实验室测试相关。更广泛的影响：自主和可编程分子装置的开发在分子尺度装置的组装和控制中有大量的关键应用。尽管这项工作将仅限于展示基本能力的试管，但在体内操作的DNAzyme医生在医学上的影响可能是巨大的。拟议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。

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.