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 problems1-3, logic circuits4-6 and robotics7-9. The molecule also naturally interfaces with living systems, and different forms of DNA-based biocomputing have previously been demonstrated10-13. Here we show that DNA origami14-16 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 employed the DNA origami robots in living cockroaches (Blaberus discoidalis) to control a molecule that targets the cells of the animal.

Synthetic biology devices for in vitro and in vivo diagnostics

“…Only cell typespecific surface antigen "keys" can unlock the barrel, which then spills its contents like an entropic spring, labeling the target cell or influencing its signaling pathways. Although there is great potential for such tools, the in vivo susceptibility of DNA-based nanorobots to degradation must be addressed before use in humans; but, encouragingly, nanorobots have been successfully demonstrated in live insects (86). Solutions to resolve degradation issues have been drawn from the architecture of membrane-encapsulated viruses, with lipid bilayer-coated DNA nanostructures displaying dramatically increased in vivo half-life (87).…”

Beyond the smiley face: applications of structural DNA nanotechnology

“…In addition to its use in nanocircuitry, DNA origami has also been shown to serve as a natural interface within living systems; that is, as a biocomputing method [34]. DNA origami based nanoscale robots were created, and their interactions in living cockroaches were utilized to switch molecular payloads (‘logic gates’) either ‘on’ or ‘off’ [34].…”

“…DNA origami based nanoscale robots were created, and their interactions in living cockroaches were utilized to switch molecular payloads (‘logic gates’) either ‘on’ or ‘off’ [34]. …”

The utility of DNA nanostructures for drug delivery in vivo

“…Bachelet and his team have studied a barrel-shaped DNA nanorobot inside living cockroaches (Blaberus discoidalis) [8]. Intriguingly, the study shows that dynamic DNA structures can perform simple Boolean computations in a living animal.…”