A novel replicating circular DNAzyme

Nucleic Acids Res. 2004 Apr 28;32(8):2336-41. doi: 10.1093/nar/gkh547. Print 2004.

Abstract

10-23 DNAzyme has the potential to suppress gene expressions through sequence-specific mRNA cleavage. However, the dependence on exogenous delivery limits its applications. The objective of this work is to establish a replicating DNAzyme in bacteria using a single-stranded DNA vector. By cloning the 10-23 DNAzyme into the M13mp18 vector, we constructed two circular DNAzymes, C-Dz7 and C-Dz482, targeting the beta-lactamase mRNA. These circular DNAzymes showed in vitro catalytic efficiencies (kcat/K(M)) of 7.82 x 10(6) and 1.36 x 10(7) M(-1) x min(-1), respectively. Their dependence on divalent metal ions is similar to that found with linear 10-23 DNAzyme. Importantly, the circular DNAzymes were not only capable of replicating in bacteria but also exhibited high activities in inhibiting beta-lactamase and bacterial growth. This study thus provides a novel strategy to produce replicating DNAzymes which may find widespread applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Catalysis / drug effects
  • Cations, Divalent / pharmacology
  • DNA, Catalytic / biosynthesis*
  • DNA, Catalytic / genetics*
  • DNA, Catalytic / metabolism
  • DNA, Circular / biosynthesis*
  • DNA, Circular / genetics
  • DNA, Circular / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Genetic Engineering*
  • Genetic Vectors / genetics
  • Magnesium / pharmacology
  • beta-Lactamases / biosynthesis
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Cations, Divalent
  • DNA, Catalytic
  • DNA, Circular
  • beta-Lactamases
  • Magnesium