In vitro cleavage of hepatitis B virus C mRNA by 10-23 DNA enzyme

Hepatobiliary Pancreat Dis Int. 2005 Nov;4(4):573-6.

Abstract

Background: 10-23 DNA enzyme is one kind of deoxyribozymes for RNA cleavage. The inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in HepG2.2.15 cells were demonstrated previously. The aim of this study was to further explore the cleavage activities of 10-23 DNA enzyme targeting at HBV C gene mRNA in vitro.

Methods: 10-23 DNA enzyme named Drz-HBV-C-9 specific to HBV C gene ORF A(1816)UG was designed and synthesized. HBV C gene mRNA was obtained by the in vitro transcription method. Cleavage activities of Drz-HBV-C-9 were observed in vitro. Values of kinetic parameters including Km,Kcat and Kcat/Km were calculated accordingly.

Results: Under the certain cleavage conditions, Drz-HBV-C-9 could efficiently cleave target mRNA at specific sites in vitro. Cleavage products of 109nt plus 191nt were obtained. The kinetic parameters, Km, Kcat and Kcat/Km for Drz-HBV-C-9, were 1.4 X 10(-9) mol, 1.6 min-1 and 1.1 X 10(9) mol(-1) x min(-1), respectively.

Conclusions: 10-23 DNA enzyme targeting at HBV C gene mRNA possesses specific cleavage activities in vitro. This would be a potent antiviral strategy with respect to HBV gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents
  • Base Sequence
  • Codon / genetics
  • DNA Primers
  • DNA, Catalytic / genetics
  • DNA, Catalytic / metabolism*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism*
  • Hepatitis B virus / enzymology
  • Hepatitis B virus / genetics*
  • Kinetics
  • Open Reading Frames
  • RNA, Messenger / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Substrate Specificity
  • Transcription, Genetic

Substances

  • Antiviral Agents
  • Codon
  • DNA Primers
  • DNA, Catalytic
  • DNA, Single-Stranded
  • RNA, Messenger
  • RNA, Viral
  • RNA-cleaving DNA 10-23