DNAzymes: Selected for Applications

Abstract

DNA‐based enzymes, also known as deoxyribozymes or DNAzymes, are single‐stranded DNA molecules with catalytic activity. DNAzymes do not exist in nature but can be isolated from random‐sequence DNA pools using in vitro selection. To date, many DNAzymes that collectively catalyze a diverse range of chemical transformations have been reported. Here, examples of new DNAzymes engineered to mimic some intriguing functions of naturally occurring protein‐based enzymes are discussed. This is followed by discussions of recent examples of a particular class of DNAzymes, known as “RNA‐cleaving DNAzymes”, that have been derived specifically so that their activity is strictly dependent on a given chemical or biological stimulus. Some unique ways to employ ligand‐responsive DNAzymes for the design of bioanalytical assays and biosensors are then highlighted. Being DNA molecules, DNAzymes have proven to be entirely compatible with DNA amplification. Several approaches are then discussed, which relay the activity of an analyte‐activated DNAzyme into the production of massive amounts of DNA amplicons, via “rolling circle amplification”, in biosensing applications designed to deliver very high levels of detection sensitivity.

A DNA‐Mediated Chemically Induced Dimerization (D‐CID) Nanodevice for Nongenetic Receptor Engineering To Control Cell Behavior

“…Aside from aptamers, DNAzymes also display recognition functions through their cofactor‐responsive catalytic activity. However, their application in manipulating cell receptors remains unexplored. By replacing r with an DNAzyme, we extended the responsiveness of D‐CID to more chemical substance classes, such as amino acids (e.g., l ‐histidine) and ions (e.g., Zn 2+ ).…”

A DNA‐Mediated Chemically Induced Dimerization (D‐CID) Nanodevice for Nongenetic Receptor Engineering To Control Cell Behavior

“…Herein, we present anew nongenetic approach to regulate receptor dimerization and control cell behavior using aDNAmediated CID (D-CID) nanodevice.C ompared with canonical CID approaches requiring chimeric receptors, [6] D-CID uses DNA-based nanodevices to act on endogenous receptors,t riggering DNAs trand displacement for receptor dimerization. Owing to the versatile modalities of functional DNAs (e.g., aptamers and DNAzymes), [8] the rational moduluar design of D-CID can be applied to various smallmolecular cues,p roviding excellent flexibility for receptor activation. Furthermore,the multi-input properties of D-CID allows for manipulating the behavior of multiple cell populations simultaneously in ap redictable and designable manner,e nabling spatial and temporal control of desired cell behavior in complex cell mixtures.W eb elieve that the proposed D-CID nanodevice will have broad applicability in cell therapy and regenerative medicine.…”

Tailored Transition‐Metal Coordination Environments in Imidazole‐Modified DNA G‐Quadruplexes

“…The simple phosphoramidite-based approachw ill allow for the expansion of the family of DNAzymesw ith members showingu nprecedented functionality. [21] Our concept even allows to introducea na dditional level of complexity by mixingd ifferent types of ligands, such as carboxylate or thiol groups,w ith the herein presentedi midazole moieties, to create nonstatistical heteroleptic environments, a challenge that we are currently pursuing.…”