New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury

Nat Med. 1999 Nov;5(11):1264-9. doi: 10.1038/15215.

Abstract

Early growth response factor-1 (Egr-1) binds to the promoters of many genes whose products influence cell movement and replication in the artery wall. Here we targeted Egr-1 using a new class of DNA-based enzyme that specifically cleaved Egr-1 mRNA, blocked induction of Egr-1 protein, and inhibited cell proliferation and wound repair in culture. The DNA enzyme also inhibited Egr-1 induction and neointima formation after balloon injury to the rat carotid artery wall. These findings demonstrate the utility of DNA enzymes as biological tools to delineate the specific functions of a given gene, and implicate catalytic nucleic acid molecules composed entirely of DNA as potential therapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blood
  • Cell Division / genetics*
  • Cells, Cultured
  • DNA, Single-Stranded / metabolism*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Early Growth Response Protein 1
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hydrolysis
  • Immediate-Early Proteins*
  • Immunohistochemistry
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / injuries
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Rats
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA enzyme ED5
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Immediate-Early Proteins
  • RNA, Messenger
  • Transcription Factors