Prototype DNA Enzyme Drug Stops Cancer Growth

While enzymes are usually proteins, a team of researchers has used a novel DNA enzyme (DNAzyme) to inhibit the c-Jun transcription factor, a principal regulator of inflammation and cancer cell growth.

A DNAzyme is a DNA molecule with a catalytic action. These substances are also referred to as deoxyribozymes, DNA enzymes, and catalytic DNA. DNAzymes are associated with gene replication only, and they exist only in the laboratory, but there they are very powerful research tools. DNAzymes were first used in lead-ion dependent RNA cleaving. In the 10 or so years since, many other DNAzymes have been created, each with a specific action. DNA ligases are particularly interesting because they are exceptionally chemoselective when applied to RNA branching reactions, with each ligase adhering to only one specific branch. DNAzymes are also used as metal biosensors, detecting heavy metals completely organically.


Investigators at the University of New South Wales (Sydney, AU; www.unsw.ed.au) used the DNAzyme Dz13 to inhibit c-Jun expression in squamous cell carcinoma (SCC) cells. They found that Dz13 inhibited SCC proliferation and suppressed solid SCC tumor growth and tumor angiogenesis in severe combined immunodeficient mice. Dz13 also suppressed the expression of vascular endothelial growth factor and fibroblast growth factor-2 in the tumors. These findings were reported in the June 19, 2006, online edition of Oncogene.


In a second paper published in the July 2006 issue of Nature Biotechnology, inhibition of c-Jun by Dz13 was shown to reduce joint swelling, inflammatory cell infiltration, and bone erosion in a mouse model of rheumatoid arthritis.

"C-Jun is an important disease-causing gene,” said senior author Dr. Levon Khachigian, professor of molecular biology at the University of New South Wales. "It stands out because we do not see much of it in normal tissue, but it is highly expressed in diseased blood vessels, eyes, lungs, joints, and in the gut--in any number of areas involving inflammation and aggressive vascular growth. Our experimental drug, Dz13, is like a secret agent that finds its target, c-Jun, within the cell and destroys it. Conventional anti-inflammatory drugs are associated with a whole host of side effects. Our therapeutic may potentially avert some of these.”




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University of New South Wales