DNA-Based Drug Protects the Damaged Heart after Myocardial Infarction

Still, this variety, together with single-stranded and double-stranded domains, can give complex structures that, much like enzymes, can selectively bind substrates and catalyze useful chemical reactions. Such nucleic acid based catalysts are called DNAzymes and hold great promise as chemical sensors; tools to construct nanostructures; and molecular machines and computing systems.

Investigators from the University of New South Wales (Sydney, Australia) took advantage of DNA's structural stability and catalytic activity while designing a drug directed at the c-Jun gene. This gene is only poorly expressed in normal cardiac muscle but is induced within 24 hours of heart attack or perfusion treatment. The protein produced by c-Jun acts to provoke inflammation of heart tissue and triggers apoptosis of heart muscle cells.

In the July 17, 2009, online edition of the journal Arteriosclerosis, Thrombosis and Vascular Biology, the investigators reported that the DNAzyme Dz13 specifically targeted and neutralized the c-Jun gene. The drug prevented proinflammatory immune cells from infiltrating into injured heart tissue and protected the heart cells from apoptosis. Dz13 also improved heart function without influencing myocardial vascularity or fibrosis.

"While this drug does not prevent the heart attack, it does reduce the damaging effects of the blockage on the heart once it has happened,” said senior author Dr. Levon Khachigian, professor of vascular research at the University of New South Wales. "It is a targeted therapy that can be used to complement other procedures and improve chances of a normal recovery. We have been able to develop a drug to silence a disease-triggering gene. The drug improves heart function, regardless of whether it is administered at the time of the heart attack, or at the time of the revascularization process.”

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University of New South Wales