Stimuli‐Responsive RNA‐Cleaving DNAzyme for Biomedical Application

Abstract

Analysis & Sensing www.analysis-sensing.org Review doi.org/10.1002/anse.202200065DNAzymes are synthetic deoxynucleotide oligomers with catalytic properties selected through in vitro systematic evolution of ligands by exponential enrichment (SELEX) technique. RNAcleaving DNAzymes have attracted increasing attentions in bioanalysis and biomedical applications due to their simple synthesis and modification, stable structure, and high catalytic activity. Especially, their different modes of activity regulation enable their extensive theranostic development. This review introduces the in vitro selection of DNAzymes and some typical ones, followed by the description of various stimuli-responsive regulation strategies on DNAzyme activity, including metal ion cofactors, small molecules, protease, light, and heat. Then the recent advances of DNAzyme-based biosensors, therapeutic applications, cell-cell interaction regulation, and logic operation are summarized. At last, the current challenges and possible development of DNAzyme-based biosensors are discussed.

DNA response element-based smart drug delivery systems for precise drug release

“…Owing to the high catalytic activity and structural identification of DNAzymes, DNAzyme-based DDSs have been widely applied to gene therapy or combined gene therapy by specifically cleaving target mRNA and inhibiting the expression of the corresponding protein. Nevertheless, their low effectiveness in vivo, [96][97][98] arising from low delivery efficiency, instability, and the lack of sufficient cofactors, hinders the development of DNAzymes for clinical application. To address this issue, more attention should be paid to developing DDSs to enhance their cellular uptake, modifications to improve their stability, and smart systems to generate sufficient cofactors in situ.…”

“…To address this issue, more attention should be paid to developing DDSs to enhance their cellular uptake, modifications to improve their stability, and smart systems to generate sufficient cofactors in situ. [96][97][98]…”

Nucleic Acids Enabled‐Interfacial Engineering for Biomarker Sensing with Distance Constraint Effects

“…Until now, diverse functions of DNAzymes have been discovered, ranging from DNA and RNA cleavage, DNA phosphorylation, porphyrin metallotransferase, DNA kinase, to DNA capping. [83] Among them, two classes of DNAzyme have been used extensively in the detection of biomarkers: RNA-cleaving DNAzymes (RCDs) and peroxidase mimicking DNAzymes (PMDs). [84,85] RCDs can promote the sitespecific cleavage reaction of an RNA dinucleotide junction, generating two cleavage fragments; PMDs can coordinate with hemin to oxidase substrates, producing colorimetric and chemiluminescent signals when hydrogen peroxide exists.…”