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Universal computing by DNA origami robots in a living animal

Abstract

Biological systems are collections of discrete molecular objects that move around and collide with each other. Cells carry out elaborate processes by precisely controlling these collisions, but developing artificial machines that can interface with and control such interactions remains a significant challenge. DNA is a natural substrate for computing and has been used to implement a diverse set of mathematical problems1,2,3, logic circuits4,5,6 and robotics7,8,9. The molecule also interfaces naturally with living systems, and different forms of DNA-based biocomputing have already been demonstrated10,11,12,13. Here, we show that DNA origami14,15,16 can be used to fabricate nanoscale robots that are capable of dynamically interacting with each other17,18 in a living animal. The interactions generate logical outputs, which are relayed to switch molecular payloads on or off. As a proof of principle, we use the system to create architectures that emulate various logic gates (AND, OR, XOR, NAND, NOT, CNOT and a half adder). Following an ex vivo prototyping phase, we successfully used the DNA origami robots in living cockroaches (Blaberus discoidalis) to control a molecule that targets their cells.

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Figure 1: Robots emulating AND, OR, XOR gates and a half adder in a living animal.
Figure 2: Robots emulating NAND and NOT gates in a living animal.
Figure 3: Robots emulating the reversible CNOT gate in a living animal.
Figure 4: A hypothetical system capable of simultaneously controlling three therapeutic molecules.

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Acknowledgements

The authors thank the following colleagues for their valuable advice and comments on the manuscript: A. Adamatzky, S. Revzen, D.Y. Zhang, R. Jungmann, P. Yin, A. Marblestone, E. Shapiro, A. Munitz, A. Binshtok, L. Qian, E. Winfree and G.M. Church. The authors are particularly grateful to S.M. Douglas for valuable contributions. The authors acknowledge the members of the Bachelet lab at Bar Ilan University for support, technical help and valuable discussions. This work was supported by a European Research Council Starting grant (no. 335332) to I.B., a Kamin grant from the Israeli Ministry of Industry & Commerce to I.B. and grants from the Faculty of Life Sciences and the Institute of Nanotechnology & Advanced Materials at Bar-Ilan University.

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All authors designed the experiments. Y.A., E.B.I, S.I., A.A.H. and I.B. performed experiments. All authors contributed to writing the manuscript.

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Correspondence to Ido Bachelet.

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The authors declare no competing financial interests.

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Amir, Y., Ben-Ishay, E., Levner, D. et al. Universal computing by DNA origami robots in a living animal. Nature Nanotech 9, 353–357 (2014). https://doi.org/10.1038/nnano.2014.58

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