Universal computing by DNA origami robots in a living animal

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

Designing a Bio-responsive Robot from DNA Origami

Nucleic acids are astonishingly versatile. In addition to their natural role as storage medium for biological information(1), they can be utilized in parallel computing(2,3) , recognize and bind molecular or cellular targets(4,5) , catalyze chemical reactions(6,7) , and generate calculated responses in a biological system(8,9). Importantly, nucleic acids can be programmed to self-assemble into 2D and 3D structures(10-12), 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 Seeman(13), and several variations on this theme have since been realized using various techniques(11,12,14,15) . However, the most significant is perhaps the one proposed by Rothemund, termed scaffolded DNA origami(16). 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 well(17,18) . The current paper will focus on the caDNAno 2.0 software(19) 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 described(20). 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 Cando(21) to simulate the mechanical properties of the designed shape. The concept we discuss can be adapted to multiple tasks and settings

Nanoscale Robots Exhibiting Quorum Sensing

Multi-agent systems demonstrate the ability to collectively perform complex tasks (e.g., construction, search, and locomotion) with greater speed, efficiency, or effectiveness than could a single agent alone. Direct and indirect coordination methods allow agents to collaborate to share information and adapt their activity to fit dynamic situations. A well-studied example is quorum sensing (QS), a mechanism allowing bacterial communities to coordinate and optimize various phenotypes in response to population density. Here we implement, for the first time, bio-inspired QS in robots fabricated from DNA origami, which communicate by transmitting and receiving diffusing signals. The mechanism we describe includes features such as programmable response thresholds and quorum quenching, and is capable of being triggered by proximity of a specific target cell. Nanoscale robots with swarm intelligence could carry out tasks that have been so far unachievable in diverse fields such as industry, manufacturing, and medicine. </jats:p

Universal computing by DNA origami robots in a living animal

These authors contributed equally to this work. 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

A Non-Newtonian Fluid Robot

New types of robots inspired by biological principles of assembly, locomotion, and behavior have been recently described. In this work we explored the concept of robots that are based on more fundamental physical phenomena, such as fluid dynamics, and their potential capabilities. We report a robot made entirely of non-Newtonian fluid, driven by shear strains created by spatial patterns of audio waves. We demonstrate various robotic primitives such as locomotion and transport of metallic loads—up to 6-fold heavier than the robot itself—between points on a surface, splitting and merging, shapeshifting, percolation through gratings, and counting to 3. We also utilized interactions between multiple robots carrying chemical loads to drive a bulk chemical synthesis reaction. Free of constraints such as skin or obligatory structural integrity, fluid robots represent a radically different design that could adapt more easily to unfamiliar, hostile, or chaotic environments and carry out tasks that neither living organisms nor conventional machines are capable of. </jats:p

An antiviral self-replicating molecular heterotroph

AbstractWe report the synthesis of a molecular machine, fabricated from nucleic acids, which is capable of digesting viral RNA and utilizing it to assemble additional copies of itself inside living cells. The machine’s body plan combines several parts that build upon the target RNA, assembling an immobile, DNA:RNA 4-way junction, which contains a single gene encoding a hammerhead ribozyme (HHR). Full assembly of the machine’s body from its parts enables the subsequent elongation of the gene and transcription of HHR molecules, followed by HHR-mediated digestion of the target molecule. This digestion converts the target to a building block suitable for participation in the assembly of more copies of the machine, mimicking biological heterotrophy. In this work we describe the general design of a prototypical machine, characterize its activity cycle and kinetics, and show that it can be efficiently and safely delivered into live cells. As a proof of principle, we constructed a machine that targets the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) GP64 gene, and show that it effectively suppresses viral propagation in a cell population, exhibiting predator/prey-like dynamics with the infecting virus. In addition, the machine significantly reduced viral infection, stress signaling, and innate immune activation inside virus-infected animals. This preliminary design could control the behavior of antisense therapies for a range of applications, particularly against dynamic targets such as viruses and cancer.</jats:p