Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Nucleic Acids Res. 2022 Nov 28;50(21):12578-12595. doi: 10.1093/nar/gkac1120.
The use of synthetic biological circuits to deal with numerous biological challenges has been proposed in several studies, but its implementation is still remote. A major problem encountered is the complexity of the cellular engineering needed to achieve complex biological circuits and the lack of general-purpose biological systems. The generation of re-programmable circuits can increase circuit flexibility and the scalability of complex cell-based computing devices. Here we present a new architecture to produce reprogrammable biological circuits that allow the development of a variety of different functions with minimal cell engineering. We demonstrate the feasibility of creating several circuits using only a small set of engineered cells, which can be externally reprogrammed to implement simple logics in response to specific inputs. In this regard, depending on the computation needs, a device composed of a number of defined cells can generate a variety of circuits without the need of further cell engineering or rearrangements. In addition, the inclusion of a memory module in the circuits strongly improved the digital response of the devices. The reprogrammability of biological circuits is an intrinsic capacity that is not provided in electronics and it may be used as a tool to solve complex biological problems.
已有多项研究提出使用合成生物电路来应对众多生物学挑战,但其实践仍遥不可及。所遇到的一个主要问题是,实现复杂的生物电路需要复杂的细胞工程,而且缺乏通用的生物系统。可编程电路的产生可以提高电路的灵活性和复杂基于细胞的计算设备的可扩展性。在这里,我们提出了一种新的架构来产生可编程生物电路,这些电路允许在最小的细胞工程基础上开发各种不同的功能。我们证明了仅使用一小部分工程细胞就可以创建几种电路的可行性,这些电路可以通过外部编程,根据特定输入实现简单的逻辑。在这方面,根据计算需求,由若干定义明确的细胞组成的设备可以生成各种无需进一步细胞工程或重新排列的电路。此外,在电路中加入记忆模块会大大增强设备的数字响应。生物电路的可编程性是电子学所不具备的固有能力,它可以用作解决复杂生物学问题的工具。