MSGID: 1:317/3 6459cc5c   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Scientists develop gene silencing DNA enzyme that can target a single   
   molecule    
    Breakthrough holds promise for disease treatments, precision medicine   
      
      
     Date:   
         May 8, 2023   
     Source:   
         University of California - Irvine   
     Summary:   
         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   
         revolutionize the development of DNAzymes for treating cancer,   
         infectious diseases and neurological disorders.   
      
      
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   FULL STORY   
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   Researchers from the University of California, Irvine 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 revolutionize 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 percent of all human   
   cancers. A description of how the team achieved this enzyme evolution   
   was recently published in the online journal Nature Communications.   
      
   "Generating DNAzymes that can effectively function in the natural   
   conditions of cell systems has been more challenging than expected,"   
   said corresponding author John Chaput, UCI professor of pharmaceutical   
   sciences. "Our results suggest that chemical evolution could pave the   
   way for development of novel therapies for a wide range of diseases."   
   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.   
      
   "We solved that problem by re-engineering the DNAzyme using chemistry to   
   reduce its dependency on magnesium and did so in such a way that we could   
   maintain high catalytic turnover activity," Chaput said. "Ours is one of   
   the very first, if not the first, example of achieving that. The next   
   steps are to advance Dz 46 to a point that it's ready for pre-clinical   
   trials."  Team members Kim Thien Nguyen, project scientist, and Turnee   
   N. Malik, postdoctoral scholar, both from the Department of Pharmaceutical   
   Sciences, also participated in this study.   
      
   The researchers and UCI have filed provisional patent applications on   
   the chemical composition and cleavage preference of Dz 46. Chaput is a   
   consultant for drug development company 1E Therapeutics, which supported   
   this work.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Genes # Human_Biology # Gene_Therapy   
             o Mind_&_Brain   
                   # Autism # Huntington's_Disease # Disorders_and_Syndromes   
             o Plants_&_Animals   
                   # Biochemistry_Research # Biotechnology # Genetics   
       * RELATED_TERMS   
             o Telomere o Genetic_code o Chemotherapy o DNA o   
             Stem_cell_treatments o Gene o Gene_therapy o Vector_(biology)   
      
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   Story Source: Materials provided by   
   University_of_California_-_Irvine. Note: Content may be edited for style   
   and length.   
      
      
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   Journal Reference:   
      1. Kim Nguyen, Turnee N. Malik, John C. Chaput. Chemical evolution   
      of an   
         autonomous DNAzyme with allele-specific gene silencing   
         activity. Nature Communications, 2023; 14 (1) DOI:   
         10.1038/s41467-023-38100-9   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230508190607.htm   
      
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