## 3 DNA Origami Devices with Molecular Interactions
DNA origami devices with specific interactions with other biomolecules of interest can be constructed with the help of aptamers. Aptamers are oligonucleotides which bind a specific target molecule with high affinity. One type of dynamic aptamer-functionalized system is a container that is held closed by the aptamer regions hybridized to complementary DNA strands [12; 90]. The container is released into an open state when the aptamers come in contact and bind to their target molecule, which creates an intriguing potential to use these types of DNA devices as specifically targeted drug-delivery vehicles. A famous example of an aptamer-functionalized DNA origami container is a logic-gated nanorobot introduced by [PERSON] et al. [12] (Figure 2c). The robots were equipped with different combinations of aptamers. The robot held in a closed state would open and release its cargo only when two different triggers were simultaneously encountered, thus creating a logical AND-gate. In a later study, [PERSON] et al. [91] developed the idea of recreating logical functions and performing molecular computing using DNA nanorobots even further. When aptamer-functionalized robots were mixed in defined molar ratios with robots that could either activate or deactivate the original robots via DNA-DNA interactions, the robot mixtures could emulate a variety of logical functions and perform rudimentary computing inside living cockroaches. Recently, it was demonstrated that a mixture of three interacting robots (similar to those in Reference [91]) could behave according to [PERSON]'s three laws of robotics [92; 93]. With these logic-gated DNA nanorobots and a microRNA molecule (a human miR-16 analog) as a damage signal of the system, the authors were able to recreate [PERSON]'s famous \"Runaround\" scenario (dynamics between robot populations), using approximately 100 billion robots [92]. Figure 2: DNA origami devices with molecular interactions. (**a**) DNA origami pliers or forceps that exhibit conformational change upon a target molecule binding [84]; (**b**) A DNA origami measurement device equipped by nucleosomes to probe nucleosome-nucleosome interaction [85]; (**c**) A logic-gated nanorobot that displays cargo when specific antigens bind to aptamer-encoded DNA locks [12]; (**d**) DNA origami twisting and rotation through the application of DNA intercalating molecules [94]; (**a**) is reproduced with permission from the authors of [84], published by Nature Publishing Group, 2011; (**b**) is reproduced with permission from the authors of [85], published by The American Association for the Advancement of Science, 2017; (**c**) is reproduced with permission from the authors of [12], copyright The American Association for the Advancement of Science, 2012; (**d**) is reproduced with permission from the authors of [94], copyright American Chemical Society, 2016. Recently, the in vivo therapeutic potential of aptamer-functionalized DNA origami nanorobots was shown by [PERSON] et al. [90], who designed a tubular DNA origami device by rolling up 2D origami sheet with the help of nucleolin-binding aptamers. The devices were shown to unroll and expose active thrombin in the vicinity of targeted endothelial tumor cells, leading to the inhibition of tumor growth. Dynamic DNA origami devices are often constructed by linking rigid dsDNA elements with flexible hinges or pivot points formed of ssDNA. [PERSON] et al. [94] studied the possibility of inducing controllable dynamic behavior in structures consisting solely of dsDNA. They utilized DNA-binding adducts, such as ethidium bromide (EtBr), which intercalate between DNA base pairs and cause torsional deformation of dsDNA by unwinding the duplex. By increasing the intercalator concentration in the solution, they demonstrated a significant twist along the length of the whole DNA origami (Figure 2d). The change was shown to be fine-tunable via intercalator concentration, and partially reversible when intercalators were removed via the addition of competing DNA strands.