Autonomous programmable DNA nanorobotic devices using DNAzymes

A major challenge in nanoscience is the design of synthetic molecular devices that run autonomously (that is, without externally mediated changes per work-cycle) and are programmable (that is, their behavior can be modified without complete redesign of the device). DNA-based synthetic molecular devices have the advantage of being relatively simple to design and engineer, due to the predictable secondary structure of DNA nanostructures and the well-established biochemistry used to manipulate DNA nanostructures. However, ideally we would like to minimize the use of protein enzymes in the design of a DNA-based synthetic molecular device. We present the design of a class of DNA-based molecular devices using DNAzyme. These DNAzyme-based devices are autonomous, programmable, and further require no protein enzymes. The basic principle involved is inspired by a simple but ingenious molecular device due to Tian et al. [Y. Tian, Y. He, Y. Chen, P. Yin, C. Mao, A DNAzyme that walks processively and autonomously along a one-dimensional track, Angew. Chem. Intl. Ed. 44 (2005) 4355–4358] that used DNAzyme to traverse on a DNA nanostructure, but was not programmable in the sense defined above (it did not execute computations).Our DNAzyme-based designs include (1) a finite state automaton, DNAzyme FSA that executes finite state transitions using DNAzymes, (2) extensions to it including probabilistic automaton and non-deterministic automaton, and (3) its application as a DNAzyme router for programmable routing of nanostructures on a 2D DNA addressable lattice. Furthermore, we give a medical-related application, DNAzyme doctor that provides transduction of nucleic acid expression: it can be programmed to respond to the underexpression or overexpression of various strands of RNA, with a response by the release of an RNA. (The behavior of our nucleic acid transduction devices is similar to those of the prior paper of Benenson [Y. Benenson, B. Gil, U. Ben-Dor, R. Adar, E. Shapiro, An autonomous molecular computer for logical control of gene expression, Nature 429 (2004) 423–429], but ours have the advantage that they operate without the use of any protein enzymes.)