New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury.
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.
Santiago
F S
FS
Centre for Thrombosis and Vascular Research, The University of New South Wales and Prince of Wales Hospital, Sydney, Australia.
Lowe
H C
HC
Kavurma
M M
MM
Chesterman
C N
CN
Baker
A
A
Atkins
D G
DG
Khachigian
L M
LM
D000818:Animals; D001483:Base Sequence; D001769:Blood; D002455:Cell Division / Q000235:genetics*; D002478:Cells, Cultured; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006868:Hydrolysis; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000293:injuries; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors