In vitro transcriptional and translational block of the bcl-2 gene operated by peptide nucleic acid

Biochem Biophys Res Commun. 1999 Oct 22;264(2):537-43. doi: 10.1006/bbrc.1999.1548.


The antisense and antigene activity of peptide nucleic acid (PNA) targeted to the human B-cell lymphoma (bcl)-2 gene was evaluated in vitro. Several PNAs complementary to different sequences of bcl-2, including the start codon and the 5'-untranslated region (5'-UTR), were tested. One PNA directed against the AUG start codon and another recognizing the 5'-UTR were able to specifically reduce Bcl-2 protein synthesis in a cell-free system; however, only partial inhibition (80 and 54%, respectively) was obtained when they were used singularly. Complete translation block was obtained with the simultaneous presence of both PNAs. A triplex-forming bis-PNA was targeted to a homopurine sequence on the coding strand of the bcl-2 cDNA. In an in vitro transcription assay this PNA specifically inhibited the transcription of bcl-2 at concentrations as low as 300 nM, with the concomitant appearance of a truncated 200-base-long product. These results demonstrate the ability of PNA to selectively modulate both translation and transcription of bcl-2 in vitro and suggest its potential use as an antisense and an antigene agent in order to downregulate bcl-2 expression in tumors.

MeSH terms

  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Gene Expression Regulation / drug effects
  • Genes, bcl-2 / drug effects*
  • Oligonucleotides, Antisense
  • Peptide Nucleic Acids / pharmacology*
  • Plasmids
  • Protein Biosynthesis / drug effects*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Transcription, Genetic / drug effects*


  • Oligonucleotides, Antisense
  • Peptide Nucleic Acids
  • Proto-Oncogene Proteins c-bcl-2