A DNA enzyme, or DNAzyme, has been created by researchers at the University of California, Irvine. This DNA enzyme can distinguish between two RNA strands within a cell and cut the strand associated with the disease while leaving the healthy strand intact. This “quality quieting” innovation could change the improvement of DNAzymes for treating malignant growth, irresistible illnesses, and neurological issues.
DNAzymes are cleavage enzymes made from nucleic acids. The Dz 46 enzyme, developed by researchers at UCI through chemistry, targets the KRAS gene’s master regulator of cell growth and division allele-specific RNA mutation, which is present in 25% of all human cancers. In the online journal Nature Communications, a description of how the team achieved this enzyme evolution was recently published.
According to John Chaput, a UCI professor of pharmaceutical sciences and the corresponding author, “Generating DNAzymes that can effectively function in the natural conditions of cell systems has been more challenging than expected.” Our findings suggest that new treatments for a wide range of diseases could be developed through chemical evolution.
“It has proven to be harder than anticipated to produce DNAzymes that can successfully work in cell systems’ natural environments. Our findings imply that chemical evolution may open the door to the creation of innovative treatments for a variety of ailments.”
Author John Chaput, UCI professor of pharmaceutical sciences.
Quality quieting has been accessible for over 20 years and some FDA-endorsed drugs consolidate different renditions of the innovation, yet none can recognize a solitary point change in a RNA strand. The Dz 46 enzyme has the advantage of being able to identify and eliminate a particular gene mutation, providing patients with an innovative, precision medicine treatment.
The DNAzyme, named after the Greek letter omega, accelerates chemical reactions as a catalyst. The RNA target region is bound by the “arms” on the left and right. The circle ties to magnesium, overlaps, and cuts the RNA at a quite certain site. However, since DNAzymes typically rely heavily on magnesium concentrations that are outside of a human cell, creating DNAzymes with robust multiple turnover activity under physiological conditions required some ingenuity.
According to Chaput, “We solved that problem by re-engineering the DNAzyme using chemistry to reduce its dependence on magnesium, and we did so in such a way that we could maintain high catalytic turnover activity.” “We solved that problem.” Our own is one of the absolute first, if not the first, instances of accomplishing that. DZ 46 must be advanced to the point where it is ready for pre-clinical trials as the next step.
This study also included project scientist Kim Thien Nguyen and postdoctoral scholar Turnee N. Malik, both from the Department of Pharmaceutical Sciences.
The scientists and UCI have documented temporary patent applications on the synthetic organization and cleavage inclination of Dz 46. Chaput is an expert for the drug improvement organization 1E Therapeutics, which upheld this work.
More information: Kim Nguyen et al, Chemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity, Nature Communications (2023). DOI: 10.1038/s41467-023-38100-9
