Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems^1-7. Recently, simple molecular-scale autonomous programmable computers were demonstrated^8-15 allowing both input and output information to be in molecular form. Such computers using biomolecules as input data and biologically active molecules as outputs could produce a system for 'logical' control of biological processes.

Here we show an autonomous biomolecular computer that, at least in vitro, logically analyzes the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration close to a trillion computers per microliter and consists of three programmable modules: a computation module,a stochastic molecular automaton^12-17; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded (ss)DNA molecule. In vivo applications of this approach could be bio-sensing,genetic engineering, and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyze mRNA of disease-related genes^18-22 associated with models of small-cell lung cancer (SCLC) and prostate cancer (PC), and to produce a ssDNA molecule modelled after an anti-cancer drug.