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Bioengineering

Designing a Bio-responsive Robot from DNA Origami

Published: July 8th, 2013

DOI:

10.3791/50268

1Faculty of Life Sciences and the Institute for Nanotechnology & Advanced Materials, Bar-Ilan University

DNA origami is a powerful method for fabricating precise nanoscale objects by programming the self-assembly of DNA molecules. Here, we describe how DNA origami can be utilized to design a robotic robot capable of sensing biological cues and responding by shape shifting, subsequently relayed to a desired effect.

Nucleic acids are astonishingly versatile. In addition to their natural role as storage medium for biological information1, they can be utilized in parallel computing2,3 , recognize and bind molecular or cellular targets4,5 , catalyze chemical reactions6,7 , and generate calculated responses in a biological system8,9. Importantly, nucleic acids can be programmed to self-assemble into 2D and 3D structures10-12, enabling the integration of all these remarkable features in a single robot linking the sensing of biological cues to a preset response in order to exert a desired effect.

Creating shapes from nucleic acids was first proposed by Seeman13, and several variations on this theme have since been realized using various techniques11,12,14,15 . However, the most significant is perhaps the one proposed by Rothemund, termed scaffolded DNA origami16. In this technique, the folding of a long (>7,000 bases) single-stranded DNA 'scaffold' is directed to a desired shape by hundreds of short complementary strands termed 'staples'. Folding is carried out by temperature annealing ramp. This technique was successfully demonstrated in the creation of a diverse array of 2D shapes with remarkable precision and robustness. DNA origami was later extended to 3D as well17,18 .

The current paper will focus on the caDNAno 2.0 software19 developed by Douglas and colleagues. caDNAno is a robust, user-friendly CAD tool enabling the design of 2D and 3D DNA origami shapes with versatile features. The design process relies on a systematic and accurate abstraction scheme for DNA structures, making it relatively straightforward and efficient.

In this paper we demonstrate the design of a DNA origami nanorobot that has been recently described20. This robot is 'robotic' in the sense that it links sensing to actuation, in order to perform a task. We explain how various sensing schemes can be integrated into the structure, and how this can be relayed to a desired effect. Finally we use Cando21 to simulate the mechanical properties of the designed shape. The concept we discuss can be adapted to multiple tasks and settings.

The robot we will design in this paper responds to a protein P by making a cargo C available to bind to receptors on the surface of a chosen target cell. The robot is shown in Figure 1. C may be a receptor-blocking drug; a growth factor etc., and a way to chemically link it to a DNA oligonucleotide must be available that does not destroy its function. The robot has two states. When inactive, DNA gates on the two external 'lips' are hybridized, making sure the robot remai.......

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Figures 1-25 are screenshots of the caDNAno 2.0 interface showing the design process step-by-step. The cross-section of the shape was first outlined (Figure 3), followed by automatic addition of scaffold strand fragments and completion of the entire scaffold path (Figure 7). Staple strands are automatically added (Figure 12), broken according to user-defined parameters (Figure 14), and manually edited to adapt the staples to the de.......

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DNA origami enables us to fabricate accurately defined objects with arbitrary features at the nanoscale. An important next step would be the integration of function into these designs. While many applications and challenges could be addressed with this technology, there is a particular interest in fabricating therapeutic and scientific robots from DNA origami, as these represent a natural milieu of DNA. DNA already interfaces with molecular machinery in cells as a genetic information storage medium. Interestingly,.......

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The authors wish to thank S. Douglas for extremely valuable discussions and advice, and all the members of the Bachelet lab for helpful discussions and work. This work is supported by grants from the Faculty of Life Sciences and Institute of Nanotechnology & Advanced Materials at Bar-Ilan University.

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Name Company Catalog Number Comments
Name of Reagent/Material Company Catalog Number Comments
Autodesk Maya 2012 Autodesk A student/academic account needs to be created first (see platform-specific instructions in http://cadnano.org)
caDNAno 2.0 (software) (Open source) Software for the design of DNA origami structures http://cadnano.org
Cando (webpage) (Open source) Webpage running a simulator of DNA origami shapes http://cando-dna-origami.org

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