DNAzymes in biological detection and gene therapy

Abstract

Catalytic DNA molecules (DNAzymes), produced through the systematic evolution of ligands by exponential enrichment (SELEX) process, are synthetic, single-stranded DNA molecules that either have catalytic abilities or can perform specific reactions. Among these DNAzymes, RNA-cleaving DNAzymes are the ones that can cleave RNAs at specific sites with the help of cofactors. The cofactors contains heavy metal ions (eg., Pb2+, Mg2+, Cu2+), small molecules (eg., ATP, L-histidine, Vc), bacteria (eg., Escherichia coli ) and so on. Based on the particular property, the RNA-cleaving DNAzymes are particularly promising for creating methods that can detect a wide variety of targets. For example, scientists have successfully found the Pb2+ DNAzyme, Cu2+ DNAzyme, UO22+ DNAzyme and some other specific metal ions.based DNAzymes. These DNAzymes have a high recognition specificity for the metal ions. Only when the specific metal ions existed, can the catalytic activity be performed. Besides, and the size of the catalytic activity is closely related to the concentration of metal ions. Therefore, these DNAzymes can be used to detect heavy metal ions. Similarly, the DNAzymes have been used to detect the ATP, L-histidine and Escherichia coli. What should be mentioned is that natural DNAzymes are generally D-type nucleic acids, which can be easily degraded by proteinase in physiological fluid. Therefore, in order to extend the applications of DNAzymes, emphasis has been placed on improving the selectivity and stability of DNAzymes. Based on the principle of enantiomer of nucleic acid, non-natural L-type nucleic acids have been used to prepare DNAzymes. L-type DNAzymes have similar thermal stability to D-DNAzymes, they also have better biostability and are ideal materials for constructing biosensors for complex system detection. Furthermore, based on the property of cleaving RNAs at specific sites, the DNAzymes can not only be used to detection, but also can be used to inactivate target cellular mRNA, which can be further applied in the treatment of multiple clinical disease. However, in fact, the gene therapy of DNAzymes in tumor and pathogenic microorganisms is only active in the scientific research stage, there is still a long way to realize the real clinical applications. The most prominent problem is the delivery problems, that is, how to choose a safe, efficient and specific guiding carrier to deliver DNAzyme to the target gene. In recent years, the rise of nanomedicine has brought new opportunities for gene therapy. The use of nano-sized materials to construct the drug delivery system can effectively deliver genetic drugs to tumor tissues. Nano drug carrier is an effective means to improve drug bioavailability, enhance drug stability and improve drug targeted therapy. In this review, we summarized the researches on DNAzyme-based metal ion sensors and gene treatment, and in the basis, we also outlook the possibility that whether the DNAzymes can be efficiently used to specifically detect the targets in vivo , as well as their applications of diseases therapy.