DNA computing circuits using libraries of DNAzyme subunits

Biological systems that are capable of performing computational operations(1-3) could be of use in bioengineering and nanomedicine(4,5), and DNA and other biomolecules have already been used as active components in biocomputational circuits(6-13). There have also been demonstrations of DNA/RNA-enzyme-based automatons(12), logic control of gene expression(14), and RNA systems for processing of intracellular information(15,16). However, for biocomputational circuits to be useful for applications it will be necessary to develop a library of computing elements, to demonstrate the modular coupling of these elements, and to demonstrate that this approach is scalable. Here, we report the construction of a DNA-based computational platform that uses a library of catalytic nucleic acids (DNAzymes)(10), and their substrates, for the input-guided dynamic assembly of a universal set of logic gates and a half-adder/half-subtractor system. We demonstrate multilayered gate cascades, fan-out gates and parallel logic gate operations. In response to input markers, the system can regulate the controlled expression of anti-sense molecules, or aptamers, that act as inhibitors for enzymes.