title: Meta-DNA: synthetic biology via DNA nanostructures and hybridization reactions.
abstract: 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 (ssmDNA)) 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 ssmDNA into a double-stranded mDNA (dsmDNA) and heat denaturation of a dsmDNA into its component ssmDNA, (ii) strand displacement of one ssmDNA by another, (iii) restriction cuts on the backbones of ssmDNA and dsmDNA, (iv) polymerization reactions that extend ssmDNA on a template to form a complete dsmDNA, (v) synthesis of mDNA sequences via mDNA polymerase chain reaction, (vi) isothermal denaturation of a dsmDNA into its component ssmDNA, and (vii) an isothermal replicator reaction that exponentially amplifies ssmDNA strands and may be modified to allow for mutations.
authors.affiliation: Department of Computer Science, Duke University, Durham, NC, USA. harish@cs.duke.edu
authors.forename: Harish
authors.initials: H
authors.lastname: Chandran
authors.forename: Nikhil
authors.initials: N
authors.lastname: Gopalkrishnan
authors.forename: Bernard
authors.initials: B
authors.lastname: Yurke
authors.forename: John
authors.initials: J
authors.lastname: Reif
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009693:Nucleic Acid Hybridization
chemical_list: D004247:DNA