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

非技术描述：电子设备小型化的持续进步正在无情地推动计算机技术向分子规模的设备发展。再过几个“摩尔定律周期”，组件将接近单个分子的大小，这时需要找到新的计算架构。重要的是，问题不仅仅是发展分子尺度的计算逻辑，而是将逻辑与其环境，即分子尺度环境相连接。分子逻辑电路有朝一日可能成为用于生化、纳米技术或医疗应用的嵌入式化学控制器的核心-与传统电子控制器本质上不兼容的环境。在活细胞内进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DNA的生物相容性和易于工程化，它是进行分子计算的理想物理底物。然而，目前的DNA电路并不是完全模块化的，还没有被证明在活细胞中工作。一种DNA计算的方法，其中所有的电路元件都位于DNA纳米结构上，可以帮助解决这两个挑战。技术描述：依赖于链置换机制的DNA电路构成了迄今为止最大的合理设计的分子电路。然而，要使这项技术用于实际应用，需要解决两个主要挑战。首先，需要开发真正可合成的DNA。在目前的DNA逻辑电路中，所有的元件在溶液中自由扩散，彼此随机相遇。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，要组成具有多个门的电路，每个信号和逻辑门必须使用一组不同的DNA序列来构建，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限制了可组合性，并形成了扩大DNA电路大小的主要障碍。其次，需要开发非常适合于单元内计算的体系结构。到目前为止，还没有复杂的DNA电路被证明在细胞中可靠地工作：将含有许多独立组件的电路传送到活细胞是具有挑战性的，而组装现有电路的相对简单的单链和双链组件很容易被细胞核酸酶降解。一种新的DNA计算方法，其中所有电路元件共同定位在DNA纳米结构上，将被用来解决这些看似不同的挑战。

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.