Meta-DNA: synthetic biology via DNA nanostructures and hybridization reactions

Can a wide range of complex biochemical behaviour arise from repeated applications of a highly reduced class of interactions? In particular, can the range of DNA manipulations achieved by protein enzymes be simulated via simple DNA hybridization chemistry? In this work, we develop a biochemical system which we call meta-DNA (abbreviated as mDNA), based on strands of DNA as the only component molecules. Various enzymatic manipulations of these mDNA molecules are simulated via toehold-mediated DNA strand displacement reactions. We provide a formal model to describe the required properties and operations of our mDNA, and show that our proposed DNA nanostructures and hybridization reactions provide these properties and functionality. Our meta-nucleotides are designed to form flexible linear assemblies (single-stranded mDNA ( ss mDNA)) analogous to single-stranded DNA. We describe various isothermal hybridization reactions that manipulate our mDNA in powerful ways analogous to DNA–DNA reactions and the action of various enzymes on DNA. These operations on mDNA include (i) hybridization of ss mDNA into a double-stranded mDNA ( ds mDNA) and heat denaturation of a ds mDNA into its component ss mDNA, (ii) strand displacement of one ss mDNA by another, (iii) restriction cuts on the backbones of ss mDNA and ds mDNA, (iv) polymerization reactions that extend ss mDNA on a template to form a complete ds mDNA, (v) synthesis of mDNA sequences via mDNA polymerase chain reaction, (vi) isothermal denaturation of a ds mDNA into its component ss mDNA, and (vii) an isothermal replicator reaction that exponentially amplifies ss mDNA strands and may be modified to allow for mutations.