Supporting Online Material Materials and Methods Figs. S1 to S6 Tables S1 to S4 References and Notes Scaling up Digital Circuit Computation with Dna Strand Displacement Cascades
Supporting Online Material Materials and Methods Figs. S1 to S6 Tables S1 to S4 References and Notes Scaling up Digital Circuit Computation with Dna Strand Displacement Cascades
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通讯作者：
J A Draghi;T. Parsons;G. P. Wagner;J. Plotkin;D M Weinreich;N. F. Delaney;M. DePristo;R Korona-R-Koron
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作者：
J A Draghi;T. Parsons;G. P. Wagner;J. Plotkin;D M Weinreich;N. F. Delaney;M. DePristo;R Korona-R-Koron
D. Stoebel 对手稿进行了宝贵的讨论和有益的评论。 R.E.L.将向合格的接受者提供本研究中使用的祖先和进化菌株，但须完成材料转让协议，该协议可以在本研究中构建的菌株中找到，可供合格的接受者使用。与本文报告的实验和分析相关的竞争实验计数、汇总输入数据和分析脚本已存放在为了从头开始构建复杂的生化电路，人们需要了解构建块可以有多简单以及这种电路可以如何扩展。使用基于可逆链置换过程的简单 DNA 反应机制，我们通过实验演示了几种数字逻辑电路，最终形成了包含 130 条 DNA 链的四位平方根电路。这些多层电路在每个逻辑操作中包括阈值和催化，以执行数字信号恢复，从而在具有大致恒定的开关时间和线性信号传播延迟的大型电路中实现快速可靠的功能。该设计自然地结合了大规模电路的其他关键元素，例如通用调试工具、并行电路准备以及自动电路编译器支持的抽象层次结构。生命的力量和神秘与所有细胞机器核心的信息处理纠缠在一起。工程分子信息处理系统可以让我们利用这种力量并阐明有助于我们理解和欣赏这个奥秘的原理。 DNA是一种优秀的生化电路工程材料，因为它的生物学性质支持体内技术应用，其简单的化学合成有利于体外实际实验，其组合结构提供了足够的序列设计空间，而沃森-克里克互补原理使得可预测的分子行为成为可能。自 1994 年首次演示解决七城市哈密顿路径问题以来，DNA 一直被用作计算基础 (1)，并且已经从与硅竞争发展到在分子系统中嵌入控制。虽然 DNA 自动机可以用脱氧核酶 (2, 3) 或限制性内切酶 (4) 构建，但引入立足点介导的 DNA 链置换使得无需酶的 DNA 机器能够仅通过杂交实现自动化 (5–8)。 DNA 链在自由时可充当信号，但在与互补链结合时会受到抑制。单链 DNA 信号首先可以通过称为立足点的单链结构域与部分双链复合物结合，然后释放最初的……
and D. Stoebel for valuable discussions and helpful comments on the manuscript. R.E.L. will make the ancestral and evolved strains used in this study available to qualified recipients, subject to completion of a material transfer agreement that can be found at the strains constructed in this study available to qualified recipients. Competition experiment counts, summary input data, and analysis scripts that pertain to the experiments and analyses reported in this paper have been deposited at To construct sophisticated biochemical circuits from scratch, one needs to understand how simple the building blocks can be and how robustly such circuits can scale up. Using a simple DNA reaction mechanism based on a reversible strand displacement process, we experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands. These multilayer circuits include thresholding and catalysis within every logical operation to perform digital signal restoration, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays. The design naturally incorporates other crucial elements for large-scale circuitry, such as general debugging tools, parallel circuit preparation, and an abstraction hierarchy supported by an automated circuit compiler. T he power and mystery of life is entangled within the information processing at the heart of all cellular machinery. Engineering molecular information processing systems may allow us to tap into that power and elucidate principles that will help us to understand and appreciate the mystery. DNA is an excellent engineering material for biochemical circuits because its biological nature supports technological applications in vivo, its easy chemical synthesis facilitates practical experiments in vitro, its combinatorial structure provides sufficient sequence design space, and the Watson-Crick complementarity principle enables predictable molecular behavior. DNA has been used as a computing sub-strate since the first demonstration of solving a seven-city Hamiltonian path problem in 1994 (1) and has evolved away from competing with silicon to embedding control within molecular systems. Although DNA automata can be built with deoxyribozymes (2, 3) or with restriction enzymes (4), the introduction of toehold-mediated DNA strand displacement enabled enzyme-free DNA machinery that is automated by hybrid-ization alone (5–8). A DNA strand can serve as a signal when it is free, but is inhibited when it is bound to a complementary strand. A single-stranded DNA signal can first bind to a partially double-stranded complex by a single-stranded domain called a toehold, then release the originally …