1] Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia. [2] EN-FIST Centre of Excellence, Ljubljana, Slovenia. [3].
1] Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia. [2] EN-FIST Centre of Excellence, Ljubljana, Slovenia.
Nat Chem Biol. 2014 Mar;10(3):203-8. doi: 10.1038/nchembio.1433. Epub 2014 Jan 12.
Electronic computer circuits consisting of a large number of connected logic gates of the same type, such as NOR, can be easily fabricated and can implement any logic function. In contrast, designed genetic circuits must employ orthogonal information mediators owing to free diffusion within the cell. Combinatorial diversity and orthogonality can be provided by designable DNA- binding domains. Here, we employed the transcription activator-like repressors to optimize the construction of orthogonal functionally complete NOR gates to construct logic circuits. We used transient transfection to implement all 16 two-input logic functions from combinations of the same type of NOR gates within mammalian cells. Additionally, we present a genetic logic circuit where one input is used to select between an AND and OR function to process the data input using the same circuit. This demonstrates the potential of designable modular transcription factors for the construction of complex biological information-processing devices.
由大量相同类型的逻辑门(如 NOR 门)组成的电子计算机电路可以很容易地制造出来,并可以实现任何逻辑功能。相比之下,设计的遗传电路由于细胞内的自由扩散,必须采用正交的信息介体。组合多样性和正交性可以通过可设计的 DNA 结合结构域来提供。在这里,我们利用转录激活子样抑制剂来优化正交功能完整的 NOR 门的构建,以构建逻辑电路。我们使用瞬时转染在哺乳动物细胞内实现了相同类型的 NOR 门组合的所有 16 种二输入逻辑功能。此外,我们还提出了一种遗传逻辑电路,其中一个输入用于在 AND 和 OR 功能之间进行选择,以便使用相同的电路处理数据输入。这表明可设计的模块化转录因子在构建复杂的生物信息处理设备方面具有潜力。