SHF: Medium: DNA-based Molecular Architecture with Spatially Localized Components

SHF：介质：具有空间局部化成分的基于 DNA 的分子结构

• 批准号: 1409831
• 负责人: Georg Seelig
• 金额: $ 65万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2018-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1409831&HistoricalAwards=false
• 关键词: SHF; Medium; DNA; based; Molecular

Nontechnical description: Continuing progress in the miniaturization of electronic devices is driving computer technology inexorably towards molecular scale devices. In just a few more "Moore's Law Cycles," components will approach the size of individual molecules, at which point new computing architectures need to be found. Importantly, the problem is not just to develop molecular-scale computational logic, but to interface the logic to its environment, namely a molecular-scale environment.Molecular logic circuits may one day be at the heart of embedded chemical controllers for biochemical, nanotechnological, or medical applications --- environments that are inherently incompatible with traditional electronic controllers. Performing computation inside living cells offers life-changing applications, from improved medical diagnostics to better disease therapy to intelligent drugs. Due to its bio-compatibility and ease of engineering, DNA is an ideal physical substrate for carrying out molecular computation. However, current DNA circuits are not fully modular and have not yet been demonstrated to operate in living cells. An approach to DNA computing in which all circuit elements are co-localized on a DNA nanostructure can help address both challenges.Technical description:DNA circuits that rely on the strand displacement mechanism constitute the biggest rationally designed molecular circuits by far. However, to make this technology useful for practical applications two major challenges need to be addressed. First, truly composable DNA need to be developed. In current DNA logic circuits all components diffuse freely in solution and encounter each other at random. Whether two components --- the logic gates and the signals connecting them --- react with each other depends on the chemical sequences of the components, rather than their location. Therefore, to compose a circuit with multiple gates, each signal and logic gate must be built with a different set of DNA sequences to avoid interference between gates or modules. The need to specifically design sequences of interacting components limits composability and forms a major hurdle in scaling up the size of DNA circuits. Second, architectures need to be developed that are well-suited for in-cell computing. So far, no complex DNA circuits have been demonstrated to work reliably in cells: the delivery of circuits with many independent components to living cells is challenging, and the relatively simple single and double-stranded components from which existing circuits are assembled are easily degraded by cellular nucleases. A novel approach to DNA computing in which all circuit elements are co-localized on a DNA nanostructure will be used to address these seemingly distinct challenges.

非技术描述：电子设备小型化的不断进步正在无情地推动计算机技术向分子级设备发展。再过几个“摩尔定律周期”，组件的大小将接近单个分子，此时需要找到新的计算架构。重要的是，问题不仅仅是开发分子尺度的计算逻辑，而是将逻辑与其环境（即分子尺度环境）连接起来。分子逻辑电路有一天可能成为生物化学、纳米技术、或医疗应用——本质上与传统电子控制器不兼容的环境。在活细胞内执行计算提供了改变生活的应用，从改进的医疗诊断到更好的疾病治疗再到智能药物。由于其生物相容性和易于工程化，DNA 是进行分子计算的理想物理基质。然而，目前的 DNA 电路还没有完全模块化，并且尚未被证明可以在活细胞中运行。将所有电路元件共定位在 DNA 纳米结构上的 DNA 计算方法有助于解决这两个问题。技术描述：依赖链位移机制的 DNA 电路构成了迄今为止最大的合理设计的分子电路。然而，为了使这项技术在实际应用中有用，需要解决两个主要挑战。首先，需要开发真正可组合的 DNA。在当前的 DNA 逻辑电路中，所有组件在溶液中自由扩散并随机相遇。两个组件（逻辑门和连接它们的信号）是否相互反应取决于组件的化学序列，而不是它们的位置。因此，要组成一个具有多个门的电路，每个信号和逻辑门必须用一组不同的DNA序列构建，以避免门或模块之间的干扰。需要专门设计相互作用的组件序列，这限制了可组合性，并成为扩大 DNA 电路尺寸的主要障碍。其次，需要开发非常适合单元内计算的架构。到目前为止，还没有复杂的 DNA 电路被证明可以在细胞中可靠地工作：将具有许多独立组件的电路传递到活细胞具有挑战性，并且组装现有电路的相对简单的单链和双链组件很容易被降解。细胞核酸酶。一种新颖的 DNA 计算方法将用于解决这些看似不同的挑战，其中所有电路元件都共同定位在 DNA 纳米结构上。