Biochemical and biophysical understanding of metal ion selectivity of DNAzymes

Hwang, Kyu Suk; Hosseinzadeh, Parisa; Lu, Yi

doi:10.1016/j.ica.2016.04.017

Cited by 86 publications

(60 citation statements)

References 121 publications

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“…A few Mg 2+ -dependent DNAzymes were isolated, but their activities were quite low 34. Many interesting progresses were made by using transition metal ions 7, 11, 35. Many DNAzymes were reported to use Zn 2+ 26, 36, UO 2 2+ 14, Cu 2+ 37, Cd 2+ 29, 38, Hg 2+ 39, and Ag + 40.…”

Section: Some Representative Dnazymesmentioning

confidence: 99%

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Theranostic DNAzymes

Zhou¹,

Ding²,

Liu³

2017

Theranostics

204

145

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DNAzymes are catalytically active DNA molecules that are obtained via in vitro selection. RNA-cleaving DNAzymes have attracted significant attention for both therapeutic and diagnostic applications due to their excellent programmability, stability, and activity. They can be designed to cleave a specific mRNA to down-regulate gene expression. At the same time, DNAzymes can sense a broad range of analytes. By combining these two functions, theranostic DNAzymes are obtained. This review summarizes the progress of DNAzyme for theranostic applications. First, in vitro selection of DNAzymes is briefly introduced, and some representative DNAzymes related to biological applications are summarized. Then, the applications of DNAzyme for RNA cleaving are reviewed. DNAzymes have been used to cleave RNA for treating various diseases, such as viral infection, cancer, inflammation and atherosclerosis. Several formulations have entered clinical trials. Next, the use of DNAzymes for detecting metal ions, small molecules and nucleic acids related to disease diagnosis is summarized. Finally, the theranostic applications of DNAzyme are reviewed. The challenges to be addressed include poor DNAzyme activity under biological conditions, mRNA accessibility, delivery, and quantification of gene expression. Possible solutions to overcome these challenges are discussed, and future directions of the field are speculated.

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Section: Some Representative Dnazymesmentioning

confidence: 99%

“…Since then, many different types of DNAzymes have been reported, catalyzing RNA/DNA cleavage, ligation, and phosphorylation, and other reactions 9, 11. Among them, RNA-cleaving DNAzymes have been extensively used as biosensors 6-9, and they can also be used as therapeutic agents, thus fitting the need of theranostics.…”

Section: Introductionmentioning

confidence: 99%

Theranostic DNAzymes

Zhou¹,

Ding²,

Liu³

2017

Theranostics

204

145

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“…To meet such a demand, we and others have taken advantage of DNAzymes or deoxyribozymes, which are DNA molecules capable of performing enzymatic reactions in presence of metal cofactors. [5] In this complementary approach to rational design of fluorescent sensors, metal-specific DNAzymes can be obtained by a combinatorial process called in vitro selection starting from a large DNA library of up to 10 15 combinations. [6] In this way, it is not necessary to have advanced knowledge to construct metal-binding site.…”

mentioning

confidence: 99%

“…The selection process allows the binding affinity and selectivity of the DNAzymes to be fine-tuned by introducing different levels of stringency. As a result, many DNAzymes with high selectivity have been obtained [5b,7] and then converted into metal sensors. [8] These sensors are playing key roles in environmental monitoring, including monitoring Pb 2+ in municipal water system in public schools in the US.…”

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confidence: 99%

Near‐Infrared Photothermally Activated DNAzyme–Gold Nanoshells for Imaging Metal Ions in Living Cells

et al. 2017

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DNAzymes have enjoyed success as metal ion sensors outside cells. Their susceptibility to metal-dependent cleavage during delivery into cells has limited their intracellular applications. To overcome this limitation, we herein report a near-infrared (NIR) photothermal activation method for controlling DNAzyme activity in living cells. The system consists of a three-stranded DNAzyme precursor (TSDP) whose hybridization prevents the DNAzyme from being active. After conjugating the TSDP onto gold nanoshells and upon NIR illumination, the increased temperature dehybridizes the TSDP to release the active DNAzyme, which then carries out metal ion-dependent cleavage, resulting in releasing the cleaved product containing a fluorophore. Using this construct, detecting Zn2+ in living HeLa cells is demonstrated. This method has expanded the DNAzyme versatility for detecting metal ions in biological systems under NIR light that exhibits lower phototoxicity and higher tissue penetration ability.

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“…For most other DNAzymes, metal specificity might not come from typical aptamer-type of metal binding. Despite extensive efforts, finding metal aptamers in most DNAzymes has been elusive (38,53,54). …”

Section: Resultsmentioning

confidence: 99%

A highly specific sodium aptamer probed by 2-aminopurine for robust Na⁺sensing

2016

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Sodium is one of the most abundant metals in the environment and in biology, playing critical ecological and physiological roles. Na+ is also the most common buffer salt for nucleic acids research, while its specific interaction with DNA has yet to be fully studied. Herein, we probe a highly selective and robust Na+ aptamer using 2-aminopurine (2AP), a fluorescent adenine analog. This aptamer has two DNA strands derived from the Ce13d DNAzyme. By introducing a 2AP at the cleavage site of the substrate strand, Na+ induces ∼40% fluorescence increase. The signaling is improved by a series of rational mutations, reaching >600% with the C10A20 double mutant. This fluorescence enhancement suggests relaxed base stacking near the 2AP label upon Na+ binding. By replacing a non-conserved adenine in the enzyme strand by 2AP, Na+-dependent fluorescence quenching is observed, suggesting that the enzyme loop folds into a more compact structure upon Na+ binding. The fluorescence changes allow for Na+ detection. With an optimized sequence, a detection limit of 0.4 mM Na+ is achieved, reaching saturated signal in less than 10 s. The sensor response is insensitive to ionic strength, which is critical for Na+ detection.

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Biochemical and biophysical understanding of metal ion selectivity of DNAzymes

Cited by 86 publications

References 121 publications

Theranostic DNAzymes

Theranostic DNAzymes

Near‐Infrared Photothermally Activated DNAzyme–Gold Nanoshells for Imaging Metal Ions in Living Cells

A highly specific sodium aptamer probed by 2-aminopurine for robust Na⁺sensing

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Biochemical and biophysical understanding of metal ion selectivity of DNAzymes

Cited by 86 publications

References 121 publications

Theranostic DNAzymes

Theranostic DNAzymes

Near‐Infrared Photothermally Activated DNAzyme–Gold Nanoshells for Imaging Metal Ions in Living Cells

A highly specific sodium aptamer probed by 2-aminopurine for robust Na+sensing

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A highly specific sodium aptamer probed by 2-aminopurine for robust Na⁺sensing