Chemical and structural modification of RNA-cleaving DNAzymes for efficient biosensing and biomedical applications

Wang, Qing; Wang, Zeyue; He, Yuqiu; Xiong, Bin; Li, Yingfu; Wang, Fuan

doi:10.1016/j.trac.2022.116910

Cited by 14 publications

(6 citation statements)

References 145 publications

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“…14 Although RNA-cleaving DNAzymes have been revealed to be promising tools for sensing extensive analytes, the lack of metal cofactors is an important challenge for intracellular analysis. 55 Technically, intrinsic intracellular cofactors are not sufficient for the efficient formation of the catalytic structural domain for the cleavage of substrates. It has been shown that metal cofactor-doped nanoparticles can be used to activate DNAzymes and increase their intracellular catalytic activity.…”

Section: Dnazyme-based Biosensingmentioning

confidence: 99%

RNA-cleaving DNAzymes for accurate biosensing and gene therapy

Gao¹,

Liu²,

Huo³

et al. 2023

Nanoscale

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Section: Dnazyme-based Biosensingmentioning

confidence: 99%

RNA-cleaving DNAzymes for accurate biosensing and gene therapy

Gao¹,

Liu²,

Huo³

et al. 2023

Nanoscale

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“…To overcome this problem, a number of caging-decaging strategies have been developed to enable spatiotemporal control over DNAzyme activity. [9,10] These involve the modification of the DNAzyme with a functional group that impedes the catalytic activity and can be cleaved off through an external stimulus. This concept has been realized using light, [11,12] heat, [13,14] enzymes, [15] and reactive oxygen species.…”

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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“…As a proof of concept, DNA units containing metal ion-responsive DNAzyme strands have been incorporated into the active layer of the bilayer hydrogel films to demonstrate the feasibility of the biosensing platform in detecting specific ions (Scheme B). Discovered through in vitro selection processes, DNAzymes capable of catalyzing reactions in the presence of specific cofactors offer many advantages for sensing applications, such as lower cost and higher stability than protein enzymes. − Specifically, Pb 2+ -responsive DNAzyme (GR5) and UO 2 2+ -responsive DNAzyme (39E), which can cleave RNA base-containing substrate strands in the presence of specific target ions, have been chosen as exemplary systems. − Thus, a DNA unit consisting of a DNAzyme strand and a DNA substrate strand was incorporated into the active layer of the bilayer hydrogel film. The introduction of negatively charged DNA units into the active layer imparts a nondiffusible net negative charge to the polymer network, and the internal electrostatic repulsive forces between DNA units and the high osmotic pressure induced by the rich counterions drive the swelling of the active layer to a relatively larger volume than the passive layer, resulting in the formation of a curved geometry of the bilayer film.…”

Section: Introductionmentioning

confidence: 99%

Smart Free-Standing Bilayer Polyacrylamide/DNA Hybrid Hydrogel Film-Based Sensing System Using Changes in Bending Angles as a Visual Signal Readout

Yin,

Zhang,

Liang

et al. 2024

Anal. Chem.

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Stimuli-responsive DNA hydrogels have shown great potential in sensing applications due to their attractive properties such as programmable target responsiveness, excellent biocompatibility, and biodegradability. In contrast to the extensively developed DNA hydrogel sensing systems based on the stimuli-responsive hydrogel-to-solution phase transition of the hydrogel matrix, the quantitative sensing application of DNA hydrogels exhibiting smart shape deformations has rarely been explored. Moreover, bulk DNA hydrogel-based sensing systems also suffer from high material cost and slow response. Herein, free-standing bilayer polyacrylamide/DNA hybrid hydrogel films with programmable responsive properties directed by the sequence of functional DNA units have been constructed. Compared with bulk DNA hydrogels, these DNA hydrogel films with a thickness at the micrometer scale not only greatly reduce the consumption of DNA materials but also facilitate the mass transfer of biomacromolecular substances within the hydrogel network, thus favoring their sensing applications. Therefore, a target-responsive smart DNA hydrogel film-based sensor system is further demonstrated based on the large amplitude macroscopic shape deformation of the film as a visual signal readout. As a proof of concept, Pb 2+ or UO 2 2+ ion-responsive DNA units were introduced into the active layer of the bilayer hydrogel films. In the presence of Pb 2+ or UO 2 2+ ions, the occurrence of a cleavage reaction within the DNA units leads to the release of DNA segments from the hydrogel film, inducing a dramatic shape deformation of the film, and thus sensing of Pb 2+ or UO 2 2+ ions with high specificity is achieved based on measuring the bending angle changes of these smart free-standing films. These smart DNA hydrogel film sensors with target-programmable responsiveness, simple operation, and ease of storage may hold promise for future rapid on-site testing applications.

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Chemical and structural modification of RNA-cleaving DNAzymes for efficient biosensing and biomedical applications

Cited by 14 publications

References 145 publications

RNA-cleaving DNAzymes for accurate biosensing and gene therapy

RNA-cleaving DNAzymes for accurate biosensing and gene therapy

Mechanochemical Activation of DNAzyme by Ultrasound

Smart Free-Standing Bilayer Polyacrylamide/DNA Hybrid Hydrogel Film-Based Sensing System Using Changes in Bending Angles as a Visual Signal Readout

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