In synthetic biology, the control of gene expression requires a multistep processing of biological signals. The key steps are sensing the environment, computing information and outputting products¹. To achieve such functions, the laborious, combinational networking of enzymes and substrate-genes is required, and to resolve problems, sophisticated design automation tools have been introduced². However, the complexity of genetic circuits remains low because it is difficult to completely avoid crosstalk between the circuits. Here, we have made an orthogonal self-contained device by integrating an actuator and sensors onto a DNA origami-based nanochip that contains an enzyme, T7 RNA polymerase (RNAP) and multiple target-gene substrates. This gene nanochip orthogonally transcribes its own genes, and the nano-layout ability of DNA origami allows us to rationally design gene expression levels by controlling the intermolecular distances between the enzyme and the target genes. We further integrated reprogrammable logic gates so that the nanochip responds to water-in-oil droplets and computes their small RNA (miRNA) profiles, which demonstrates that the nanochip can function as a gene logic-chip. Our approach to component integration on a nanochip may provide a basis for large-scale, integrated genetic circuits.

在合成生物学中，基因表达的控制需要生物信号的多步处理。关键步骤是感知环境，计算信息并输出产品¹。为了实现这样的功能，需要费力的酶和底物基因的组合网络，并且为了解决问题，已经引入了复杂的设计自动化工具²。但是，遗传电路的复杂度仍然很低，因为很难完全避免电路之间的串扰。在这里，我们通过将执行器和传感器集成到基于DNA折纸的纳米芯片上制成了正交的独立设备，该芯片包含酶，T7 RNA聚合酶（RNAP）和多个靶基因底物。该基因纳米芯片可正交转录其自身的基因，DNA折纸的纳米布局能力使我们能够通过控制酶与靶基因之间的分子间距离来合理设计基因表达水平。我们进一步集成了可重新编程的逻辑门，以使纳米芯片对油包水小滴做出响应并计算其小RNA（miRNA）谱，这表明纳米芯片可以用作基因逻辑芯片。