RNA-cleaving DNAzymes for accurate biosensing and gene therapy

Gao, Xin; Liu, Yan; Huo, Wendi; Song, Yinglin; Yu, Chunmei; Zhang, Jinchao; Yang, Xinjian; Yi, Jin; Liang, Xing‐Jie

doi:10.1039/d3nr01482g

Cited by 4 publications

(4 citation statements)

References 196 publications

(223 reference statements)

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“…[7] DNAzymes exhibit higher chemical and thermal stability than their RNA counterparts enabling their use in biological systems. [8] In vivo sensing applications of DNAzymes typically suffer from false positive signaling, because the co-factors are present in the biological environment, so the DNAzyme activates before reaching its target site. To overcome this problem, a number of caging-decaging strategies have been developed to enable spatiotemporal control over DNAzyme activity.…”

Section: Introductionmentioning

confidence: 99%

Mechanochemical Activation of DNAzyme by Ultrasound

Rath,

Göstl,

Herrmann

2024

Advanced Science

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Controlling the activity of DNAzymes by external triggers is an important task. Here a temporal control over DNAzyme activity through a mechanochemical pathway with the help of ultrasound (US) is demonstrated. The deactivation of the DNAzyme is achieved by hybridization to a complementary strand generated through rolling circle amplification (RCA), an enzymatic polymerization process. Due to the high molar mass of the resulting polynucleic acids, shear force can be applied on the RCA strand through inertial cavitation induced by US. This exerts mechanical force and leads to the cleavage of the base pairing between RCA strand and DNAzyme, resulting in the recovery of DNAzyme activity. This is the first time that this release mechanism is applied for the activation of catalytic nucleic acids, and it has multiple advantages over other stimuli. US has higher penetration depth into tissues compared to light, and it offers a more specific stimulus than heat, which has also limited use in biological systems due to cell damage caused by hyperthermia. This approach is envisioned to improve the control over DNAzyme activity for the development of reliable and specific sensing applications.

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Section: Introductionmentioning

confidence: 99%

Mechanochemical Activation of DNAzyme by Ultrasound

Rath,

Göstl,

Herrmann

2024

Advanced Science

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“…15,16 Due to these excellent properties, DNAzyme has already been applied to gene therapy for various diseases caused by mutations in genes such as cancer, cardiovascular disease, and viral infection. 14 Among various DNAzymes, 8−17 DNAzyme and 10−23 DNAzyme are mainly used as gene-silencing agents, which catalyze the cleavage of RNA, but 8−17 DNAzyme, which is easy to make reasonable design modifications, is considered to have a higher potential. 17,18 However, despite the many advantages of DNAzyme, they exhibit low efficacy in vivo and in cells due to issues such as insufficient stability against nuclease and low intracellular delivery efficiency.…”

Section: Introductionmentioning

confidence: 99%

“…Among these, DNAzymes, unlike other agents based on protein enzymes, consist only of DNA strands and are composed of a catalytic domain that exhibits catalytic activity by binding with a cofactor metal cation and binding domains that can bind to substrate RNA. Due to these characteristics of DNAzyme, it has the advantage of having high specificity and flexibility compared to other agents. , In particular, DNAzyme has higher physiological stability than siRNA and has higher gene-silencing efficiency than ASO, which relies on the activity of endogenous RNase H . In addition, DNAzymes have advantages such as low immunogenicity, low cost, and easy functionalization. , Due to these excellent properties, DNAzyme has already been applied to gene therapy for various diseases caused by mutations in genes such as cancer, cardiovascular disease, and viral infection …”

Section: Introductionmentioning

confidence: 99%

Nanosized DNA Hydrogel Functionalized with a DNAzyme Tetrahedron for Highly Efficient Gene Silencing

Lee,

Kim,

Lee

et al. 2024

Biomacromolecules

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DNAzymes are DNA oligonucleotides that have catalytic activity without the assistance of protein enzymes. In particular, RNA-cleaving DNAzymes were considered as ideal candidates for gene therapy due to their unique characteristics. Nevertheless, efforts to use DNAzyme as a gene therapeutic agent are limited by issues such as their low physiological stability in serum and intracellular delivery efficiency. In this study, we developed a nanosized synthetic DNA hydrogel functionalized with a DNAzyme tetrahedron (TDz Dgel) to overcome these limitations. We observed remarkable improvement in the gene-silencing effect as well as intracellular uptake without the support of gene transfection reagents using TDz Dgel. The improved catalytic activity of the DNAzyme resulted from the combination of the cell-penetrating DNA tetrahedron structure and high stability of DNA hydrogel. We envision that this approach will become a convenient and efficient strategy for gene-silencing therapy using DNAzyme in the future.

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“…This process effectively downregulates VEGF expression and triggers apoptosis in tumor cells. 17 The nanoprobe not only enables selective fluorescence imaging of survivin mRNA in live cells but also accurately distinguishes tumor cells from normal cells. Additionally, it selectively induces apoptosis in tumor cells.…”

Section: Introductionmentioning

confidence: 99%