已经通过最小误差数到12。
This research dovetails with other developments in DNA nanotechnology that are geared less towards complex computations and more towards interesting structural and dynamical features. These have resulted in robust generation of two-dimensional and three-dimensional objects from hundreds of deoxyoligo-nucleotides and in molecular-size DNA ‘walkers’. These nanostructures are often viewed as the basis for engineered biological organelles and transport, respectively.
这项研究与倾向于更复杂的计算、更有趣的结构和动力学特征的DNA纳米技术发展相吻合。这些都导致了从数百个脱氧寡核苷酸得到的健壮的二维和三维对象和化学分子尺寸的行走者。这些纳米结构往往分别被视为设计生物细胞器和运输的基础。
Supporting this notion, RNA building blocks that contain enzyme-binding aptamers have recently been shown to self-assemble into organelle-like structures in bacteria and have been reported to boost the efficiency of an enzyme-catalysed hydrogen-producing process by proximity effects. In another example, a nano-sized DNA container carrying molecular cargo was programmed to bind to cells and to open and release the cargo only when the cells expressed two surface markers simultaneously, bringing computing back into the picture and pointing towards a novel logic-driven approach to selective drug delivery in vivo.
为了支持这一观点，含有酶结合寡核苷酸适配子的RNA建筑模块最近被验证，在细胞自组装形成细胞器结构，而且已经被报道，可以通过邻近效应推进酶促 氢生产过程的效率。另一个例子中，一个DNA分子纳米集装箱运载货物的程序被绑
定到细胞上，只有在细胞的两个表面的标志同时表达时，打开和释放的货物，实现想象中的计算，指出了全新的体内逻辑驱动的选择性药物输送方法。
Tape-based biochemical state machines 基于磁带的生化状态机
The analogy between the state machine tape and biopolymers inspired ideas about molecular state machines, although the controller and the transition rules do not have obvious biological counterparts. In a number of non-autonomous theoretical blueprints, manual biochemical manipulations were proposed as the means to implement transitions. A hypothetical autono-mous Turing machine made of RNA molecules and modifying enzymes was put forward as an example of an energy-efficient computer.
状态机的磁带和生物大分子之间的类比激发了分子状态机的想法，虽然控制器和转换规则还没有明显的生物副本。在一些非自治理论的设计中，提出了人工生物化学操作的方法来实现转换。提出一个假想的RNA分子和修饰酶构成的自治图灵机，是节能计算机的一个例子。
Later, protein translation inspired a blueprint for an autonomous Turing machine as an interactive control centre of cellular processes. Experimentally, state-to-state transitions were first implemented by programmable DNA exten-sion with DNA polymerase using a template strand with ‘transition rule’ sequences. Each rule contained a binding site for the 3? end of the DNA molecule (which is the current state) and the extension template (which is the new state), such that after multiple rounds of annealing and extensions the molecule contained the history of all intermediate steps.
稍后，蛋白翻译激发了一个自治图灵机的设计，作为细胞处理的交互控制中心。
通过实验，状态转换第一次被程序化DNA 扩展模版实现，使用带有转移规则序列的模板链的DNA 聚合酶（代表新的状态）。每个规则包含一个DNA分子3?端的结合位点（代表目前的状态）和扩展模板（代表新的状态），这样在多轮的退火扩展后，分子包含所有中间步骤的历史。
Later, a finite automaton was generated in which the transitions were executed by autonomous biochemical steps based on DNA sticky-end recognition, ligation and digestion. The machine was fully programmable within its specifications — an alphabet of two symbols and the possibility of two states. This state machine was later augmented with sensory input channels that allowed it to interrogate biological signals in their native format: namely, mRNA levels.
随后，一个有限自动机产生了，交接工作基于DNA粘端识别、结扎和消化的自动生化步骤。这台机器在他的性能规范里是完全可编程的，使用一个包含两种符号的字母表和两个状态的可能性。该状态机后来增强了感觉输入通道，允许在生物信号的原有格式审查分子：即mRNA水平。
The resulting system was one of the first fully functional biochemical prototypes of a sensor– computation–actuation cycle, producing a biologically active molecular output only when a certain combination of input conditions was detected in the computer’s environment (FIG. 7b). In addition, automaton building blocks were used in molecular-level programming language. 由此产生的系统是第一个功能型生化原型传感器–计算器–周期驱动，只有当一定的输入条件组合在计算机环境中能检测到时，才产生生物活性分子输出（图7B）。此外，在分子层次的编程语言中使用了自动机构建模块。
图 7-b
Event-triggered biological state machine computation 事件触发的生物状态机的计算
This concept has been explored using recombinases and invertases as the state switches (see above) and their substrate DNA as state indicator. It was shown that a hypothetical system with 10 invertases could encode ~107 states, and an experimental circuit with two invertases was tested in bacteria. Invertase is a reversible activity, resulting in an equilibrium between two DNA sequences of opposite orientation and a mixture of different states. This was overcome in another study that used a set of invertases to count the number of chemical pulses in yeast cells.
已经使用重组酶和转化酶作为状态切换（见上文），以基底DNA为状态指示器。结果表明，用10蔗糖酶综合系统可编码107多个状态，在细菌中对两个转化酶形成的实验电路进行检测。转化酶活性是可逆的，导致两个相反方向的序列中存在一个平衡和多个状态的混合。这在另一项研究中得到了克服，在酵母细胞中使用一套转化酶计数化学脉冲的个数。
In this system, an inversion was coupled to concurrent inactivation of the invertase gene and activation of another invertase, resulting in high transition efficiencies and the required sequence of individual transitions (FIG. 7c). An event-triggered string transducer was also demonstrated biochemically; a sophisticated system of DNA-based aptamers took on different internal configurations in response to chemical inputs.
在这个系统中，一个反向被耦合到并发的一个蔗糖转化酶的失活和另一个蔗糖转化酶的激活，得到一个高的转化效率和所需的单个转换序列（图7c）。一个事件触发的字符串传感器也被生化验证；一个复杂的基于DNA的核苷酸适配子的系统，针对不同的化学输入采取不同的内部配置。
图 7-c
Methodological challenges 方法论的挑战
Biochemical and biological computing circuits present unique characterization challenges. These circuits, after they have been implemented, are indistinguishable from any natural biochemical or biological network, and they