RNA-Cleaving DNA Enzymes and Their Potential Therapeutic Applications as Antibacterial and Antiviral Agents

Abstract

DNA catalysts are synthetic single-stranded DNA molecules that have been identified by in vitro selection from random sequence DNA pools. The most prominent representatives of DNA catalysts (also known as DNA enzymes, deoxyribozymes, or DNAzymes) catalyze the site-specific cleavage of RNA substrates. Two distinct groups of RNA-cleaving DNA enzymes are the 10-23 and 8-17 enzymes. A typical RNA-cleaving DNA enzyme consists of a catalytic core and two short binding arms which form Watson–Crick base pairs with the RNA targets. RNA cleavage is usually achieved with the assistance of metal ions such as Mg2+, Ca2+, Mn2+, Pb2+, or Zn2+, but several chemically modified DNA enzymes can cleave RNA in the absence of divalent metal ions. A number of studies have shown the use of 10-23 DNA enzymes for modest downregulation of therapeutically relevant RNA targets in cultured cells and in whole mammals. Here we focus on mechanistic aspects of RNA-cleaving DNA enzymes and their potential to silence therapeutically appealing viral and bacterial gene targets. We also discuss delivery options and challenges involved in DNA enzyme-based therapeutic strategies.