Effects in live cells of a c-myc anti-gene PNA linked to a nuclear localization signal

Nat Biotechnol. 2000 Mar;18(3):300-3. doi: 10.1038/73745.


Peptide nucleic acids (PNA) are synthetic homologs of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. In this study, a PNA construct was employed as an anti-gene agent in intact cells in culture. The cell lines studied were derived from Burkitt's lymphomas (BL) that presented a translocated and hyperexpressed c-myc oncogene. A 17-mer anti-myc PNA, complementary to a unique sequence located at the beginning of the second exon of the oncogene, and was covalently linked at its N terminus to a nuclear localization signal (NLS) (PNA-myc(wt)-NLS). When BL cells were exposed to PNA-myc(wt)-NLS, the anti-gene construct was localized predominantly in the cell nuclei and a rapid consequent downregulation of c-myc expression occurred. Under these conditions, both completion of a productive cell cycle and apoptosis were inhibited.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Polyomavirus Transforming / metabolism
  • Apoptosis
  • Cell Death
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Genes, myc / genetics*
  • Humans
  • Microscopy, Confocal
  • Nuclear Envelope / drug effects
  • Nuclear Envelope / metabolism
  • Nuclear Localization Signals / genetics*
  • Peptide Nucleic Acids / pharmacology*
  • Plasmids
  • Proto-Oncogene Proteins c-myc / metabolism
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured


  • Antigens, Polyomavirus Transforming
  • Nuclear Localization Signals
  • Peptide Nucleic Acids
  • Proto-Oncogene Proteins c-myc