DNAzymeBuilder, a web application for <i>in situ</i> generation of RNA/DNA-cleaving deoxyribozymes

Mohammadi-Arani, Razieh; Javadi‐Zarnaghi, Fatemeh; Boccaletto, Pietro; Bujnicki, Janusz M.; Ponce-Salvatierra, Almudena

doi:10.1093/nar/gkac269

Cited by 8 publications

(6 citation statements)

References 44 publications

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“…Even though the results of the developed Dz activity were not presented, the described approach might become useful in designing therapeutic Dz agents. Most recently, Mohammadi-Arani et al published a web application for the design of RNA-and DNA-cleaving Dz, named DNAzymeBuilder [159]. The algorithm uses an internal database and provides as and outcome a list of Dz sequences to carry out the cleavage reaction, optimal reaction conditions, the expected yield, and the reaction products.…”

Section: Computational Selection Of Rz and Dz Sequencesmentioning

confidence: 99%

Specificity of oligonucleotide gene therapy (OGT) agents

Nedorezova¹,

Dubovichenko²,

Belyaeva³

et al. 2022

Theranostics

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Oligonucleotide gene therapy (OGT) agents (e. g. antisense, deoxyribozymes, siRNA and CRISPR/Cas) are promising therapeutic tools. Despite extensive efforts, only few OGT drugs have been approved for clinical use. Besides the problem of efficient delivery to targeted cells, hybridization specificity is a potential limitation of OGT agents. To ensure tight binding, a typical OGT agent hybridizes to the stretch of 15-25 nucleotides of a unique targeted sequence. However, hybrids of such lengths tolerate one or more mismatches under physiological conditions, the problem known as the affinity/specificity dilemma. Here, we assess the scale of this problem by analyzing OGT hybridization-dependent off-target effects (HD OTE) in vitro , in animal models and clinical studies. All OGT agents except deoxyribozymes exhibit HD OTE in vitro , with most thorough evidence of poor specificity reported for siRNA and CRISPR/Cas9. Notably, siRNA suppress non-targeted genes due to (1) the partial complementarity to mRNA 3'-untranslated regions (3'-UTR), and (2) the antisense activity of the sense strand. CRISPR/Cas9 system can cause hundreds of non-intended dsDNA breaks due to low specificity of the guide RNA, which can limit therapeutic applications of CRISPR/Cas9 by ex-vivo formats. Contribution of this effects to the observed in vivo toxicity of OGT agents is unclear and requires further investigation. Locked or peptide nucleic acids improve OGT nuclease resistance but not specificity. Approaches that use RNA marker dependent (conditional) activation of OGT agents may improve specificity but require additional validation in cell culture and in vivo .

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Section: Computational Selection Of Rz and Dz Sequencesmentioning

confidence: 99%

Specificity of oligonucleotide gene therapy (OGT) agents

Nedorezova¹,

Dubovichenko²,

Belyaeva³

et al. 2022

Theranostics

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“…Most of the circuits are programmed based on slight adjustments of several existing typical reactions. There is an urgent need to develop software that assists the design of reaction sequences, such as DNAzymeBuilder, which has been established for generation of RNA/DNA cleaving DNAzyme, which can quickly and automatically assemble DNAzymes instead of manual work [84] . DNAzyme‐based chemiluminescence and CRET systems are difficult to be efficiently transported into cells for long‐term detection and imaging.…”

Section: Discussionmentioning

confidence: 99%

Integration of Isothermal Enzyme‐Free Nucleic Acid Circuits for High‐Performance Biosensing Applications

Wang,

Shang,

Zhao

et al. 2023

ChemPlusChem

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The isothermal enzyme‐free nucleic acid amplification method plays an indispensable role in biosensing by virtue of its simple, robust, and highly efficient properties without the assistance of temperature cycling or/and enzymatic biocatalysis. Until to now, enzyme‐free nucleic acid amplification has been extensively utilized for biological assays and has achieved the highly sensitive detection of various biological targets, including DNAs, RNAs, small molecules, proteins, and even cells. In this review, the mechanisms of entropy‐driven reaction, hybridization chain reaction, catalytic hairpin assembly and DNAzyme were concisely described and their recent application as biosensors was comprehensively summarized. Furthermore, the current problems and the developments of these DNA circuits were also discussed.

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“…The selection methods should be developed into a quick, high throughput screen. Fortunately, a web, DNAzymeBuilder, has been established for generation of RNA/DNA cleaving DNAzyme, which can quickly and automatically assemble DNAzymes instead of manual work [106] . Accordingly, it is an urgent need to enhance the stability of DNAzymes and substrates by chemical modification or other carriers and design highly efficient screening means for the further development of DNAzyme‐based biomedical applications.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Stimuli‐Responsive RNA‐Cleaving DNAzyme for Biomedical Application

et al. 2022

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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.

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DNAzymeBuilder, a web application for in situ generation of RNA/DNA-cleaving deoxyribozymes

Cited by 8 publications

References 44 publications

Specificity of oligonucleotide gene therapy (OGT) agents

Specificity of oligonucleotide gene therapy (OGT) agents

Integration of Isothermal Enzyme‐Free Nucleic Acid Circuits for High‐Performance Biosensing Applications

Stimuli‐Responsive RNA‐Cleaving DNAzyme for Biomedical Application

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