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

使用成簇、规则间隔的短回文重复序列 (CRISPR) 进行人工信使 RNA 沉默，以促进高度复杂的合成遗传控制网络的组装

• 批准号: 405755-2011
• 负责人: Harris, Edouard
• 金额: $ 3.64万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Vanier Canada Graduate Scholarships - Doctoral
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=515602
• 关键词: Artificial; messenger; RNA; silencing; using

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.

合成生物学是在细胞内组装人工遗传控制通路的科学，其最终目标是创造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元件，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是更加困难的。 这主要是因为这些简单的人工成分中有许多都使用相同的信号分子来调节它们的输入。 由于细胞包含不同分子的充分搅拌的混合物，这意味着没有什么可以阻止来自一个组件的输入信号干扰另一个组件的输入信号。 该提案提出了一种新的、高度特异性的信号沉默机制作为该问题的解决方案。 通过使用被称为沉默RNA的分子，可以人为地降低细胞内发送的具有高度特异性的信号的强度。 此外，通过一些修改，沉默RNA系统可用于增加特异性输出以及减少它们。 因此，这是一种普遍适用的技术，将允许将单个组件组装成可靠的细胞决策程序，允许设计的细胞智能地感知它们的环境并做出明智的决定。 这种电池的应用及其好处是显而易见的，而且数量众多。 例如，编程细菌来识别和攻击某些类型的癌组织，杀死肿瘤而不伤害病人，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，以及赋予细菌廉价制造有用药剂的能力等。