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