In vivo repression by a site-specific DNA-binding protein designed against an oncogenic sequence

Nature. 1994 Dec 15;372(6507):642-5. doi: 10.1038/372642a0.

Abstract

A DNA-binding peptide comprising three zinc-fingers has been engineered to bind specifically to a unique nine-base-pair region of a BCR-ABL fusion oncogene in preference to the parent genomic sequences. Binding to the target oncogene in chromosomal DNA is possible in transformed cells in culture, and results in blockage of transcription. Consequently, murine cells rendered independent of growth factors by the action of the oncogene revert to factor dependence upon transient transfection with a vector expressing the peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • Feasibility Studies
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transcription, Genetic
  • Transfection
  • Zinc Fingers

Substances

  • DNA-Binding Proteins
  • Recombinant Fusion Proteins
  • DNA
  • Fusion Proteins, bcr-abl