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(GIST OF SCIENCE REPORTER) UCI Scientists develop gene silencing DNA enzyme that can target a single molecule

(July-2023)

Researchers have developed a DNA enzyme or DNAzyme — that can distinguish between two RNA strands inside a cell and cut the disease-associated strand while leaving the healthy strand intact.
This breakthrough “gene silencing” technology could revolutionise the development of DNAzymes for treating cancer, infectious diseases and neurological disorders.

DNAzymes are nucleic acid enzymes that cut other molecules. Through chemistry, UCI’s team developed the Dz 46 enzyme, which specifically targets the allele-specific RNA mutation in the KRAS gene, the master regulator of cell growth and division, found in 25 per cent of all human cancers.
A description of how the team achieved this enzyme evolution was recently published in the online journal Nature Communications.
Gene silencing has been available for more than 20 years and some FDA-approved drugs incorporate various versions of the technology, but none can distinguish a single point mutation in an RNA strand.
The benefit of the Dz 46 enzyme is that it can identify and cut a specific gene mutation, offering patients an innovative, precision medicine treatment.

The DNAzyme resembles the Greek letter omega and acts as a catalyst by accelerating chemical reactions. The “arms” on the left and right bind to the target region of the RNA.
The loop binds to magnesium, and folds and cuts the RNA at a very specific site. But generating DNAzymes with robust multiple turnover activity under physiological conditions required some ingenuity, because DNAzymes are normally very dependent on concentrations of magnesium not found inside a human cell.