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.
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Acknowledgements
We thank A. Enno for advice on immunohistochemical analysis and P. Halasz for assistance with image analysis. This work was supported in part by a Strategic Partnership with Industry grant from the Australian Research Council (L.M.K.), and grants from the National Heart Foundation of Australia (L.M.K.), National Health and Medical Research Council of Australia (N.H.M.R.C) (L.M.K. and C.N.C.) and New South Wales Health Department. H.C.L. is supported by a Medical Postgraduate Research Scholarship (N.H.M.R.C.) and L.M.K. is the recipient of an R. Douglas Wright Fellowship (N.H.M.R.C.).
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Santiago, F., Lowe, H., Kavurma, M. et al. New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury. Nat Med 5, 1264–1269 (1999). https://doi.org/10.1038/15215
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DOI: https://doi.org/10.1038/15215
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