Intellectual Merit: 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 (modifiable behavior without full redesign). DNA-based synthetic molecular devices have advantages of simplicity of design and engineering, due to predictable secondary structure and well-established biochemistry. Tasks: The main Task is optimized design and experimental demonstration of molecular devices composed of DNA strands and DNAzyme. with unique advantages of being autonomous and programmable, requiring no protein enzymes. The experiments will be executed in carefully stages of increasing complexity. First to be demonstrated is a limited ability computational device, termed a DNAzyme calculator. Next to be demonstrated is a finite state automata device, DNAzyme FSA, which executes finite state transitions using DNAzymes. Further demonstrations will be extensions to probabilistic automata and non-deterministic automata. The keystone demonstration is a DNAzyme doctor device giving transduction of nucleic acid expression: programmed to respond to under-expression or over-expression of certain nucleic acid strands that may indicate a disease, and providing a response release of appropriate strands that can act as a drug remedy. Secondary Tasks are computer software for optimized design/simulation using realistic stochastic models and correlated to laboratory tests. Broader Impact: The development of autonomous and programmable molecular devices has a vast number of critical applications in the assembly and control of molecular scale devices. Although this work will be limited to the test tube to demonstrate fundamental capabilities, the impact of a DNAzyme doctor operating in vivo could be enormous in medicine. Important educational impact of the proposed research includes the highly interdisciplinary training of graduate students and postdocs.