Artificial messenger RNA silencing using clustered, regularly interspaced short palindromic repeats (CRISPRs) to facilitate the assembly of highly complex synthetic genetic control networks

合成生物学是一门在细胞内组装人工遗传控制途径的科学，其最终目标是创造出能够根据周围环境的输入自行做出决定的设计细胞。到目前为止，已经发明和实现了许多人工组件；其中包括简单的开关、定时器、计数器和逻辑门。然而，将这些组件组合成有用的蜂窝系统已被证明更加困难。这主要是因为许多这些简单的人工成分利用相同的信号分子来调节它们的输入。由于细胞中含有搅拌良好的不同分子的混合物，这意味着没有什么可以阻止一个成分的输入信号干扰另一个成分的输入信号。本文提出了一种新的、高度特异性的信号沉默机制来解决这个问题。通过使用被称为沉默rna的分子，有可能以极大的特异性人为地降低细胞内发送的信号强度。此外，通过一些修饰，沉默RNA系统可以用来增加或减少特定的输出。因此，这是一种普遍适用的技术，可以将单个组件组装成可靠的细胞决策程序，使设计的细胞能够智能地感知环境并做出明智的决策。这种细胞的应用及其好处是显而易见的，而且数不胜数。例如，对细菌进行编程，使其识别并攻击某些类型的癌组织，在杀死肿瘤的同时不伤害患者，这可能成为可能。已经提出的其他概念包括提高生物燃料生产效率的方案，改造光合细菌以产生用于燃料电池的氢，以及赋予细菌以廉价制造有用药物制剂的能力，等等。

Synthetic biology is the science of assembling artificial genetic control pathways inside cells, with the ultimate goal of creating designer cells that are able to make decisions on their own based on inputs from the environment around them. So far, many artificial components have been invented and implemented; simple switches, timers, counters and logic gates are among these. However, combining these components into useful cellular systems has proven more difficult. This is primarily because so many of these simple artificial components make use of the same signaling molecules to regulate their inputs. Since cells contain a well-stirred mixture of different molecules, this means that there is nothing to prevent the input signals from one component from interfering with those of another. This proposal presents a new, highly specific signal silencing mechanism as a solution to this problem. Through the use of molecules known as silencing RNAs, it is possible to artificially reduce the strength of signals sent inside a cell with great specificity. Furthermore, with some modifications, the silencing RNA system may be used to increase specific outputs as well as decrease them. It is therefore a generally applicable technique that will allow for the assembly of individual components into reliable cellular decision-making programs, allowing designed cells to intelligently sense their environments and make informed decisions. The applications of such cells, and their benefits, are evident and numerous. It may become possible, for example, to program bacteria to recognize and attack certain types of cancerous tissues, killing tumours while leaving patients unharmed. Other concepts that have been proposed include schemes for increasing the efficiency of biofuel production, modifying photosynthetic bacteria to generate hydrogen for use in fuel cells, and endowing bacteria with the ability to cheaply manufacture useful pharmaceutical agents, among many others.