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Nat Nanotechnol. 2018 Oct;13(10):933-940. doi: 10.1038/s41565-018-0202-3. Epub 2018 Jul 23.

Construction of integrated gene logic-chip.

Author information

1
Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan.
2
Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
3
Graduate School of Science, Department of Chemistry, Kyoto University, Kyoto, Japan. endo@kuchem.kyoto-u.ac.jp.
4
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan. endo@kuchem.kyoto-u.ac.jp.
5
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
6
Department of Nanoscience and Nanoengineering (ASE Graduate School), Waseda University, Tokyo, Japan.
7
Research Organization for Nano & Life Innovation, Waseda University, Tokyo, Japan.
8
Department of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
9
Graduate School of Science, Department of Chemistry, Kyoto University, Kyoto, Japan. hs@kuchem.kyoto-u.ac.jp.
10
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan. hs@kuchem.kyoto-u.ac.jp.
11
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan.
12
Institute for Protein Research, Osaka University, Osaka, Japan.
13
Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan. ueda@edu.k.u-tokyo.ac.jp.
14
Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan. tadakuma@protein.osaka-u.ac.jp.
15
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan. tadakuma@protein.osaka-u.ac.jp.
16
Institute for Protein Research, Osaka University, Osaka, Japan. tadakuma@protein.osaka-u.ac.jp.

Abstract

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.

PMID:
30038365
DOI:
10.1038/s41565-018-0202-3

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