Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses

Potaczek, Daniel P.; Unger, Sebastian D.; Zhang, Nan; Τaka, Styliani; Michel, Sven; Akdağ, Nesibe; Feng, Lan; Helfer, Markus; Hudemann, Christoph; Eickmann, Markus; Skevaki, Chrysanthi; Megremis, Spyridon; Sadewasser, Anne; Alhamwe, Bilal Alashkar; Alhamdan, Fahd; Akdiş, Mübeccel; Edwards, Michael R.; Johnston, Sebastian L.; Becker, Stephan; Bachert, Claus; Papadopoulos, Nikolaos G.; Garn, Holger; Renz, Harald

doi:10.1016/j.jaci.2018.07.026

Cited by 24 publications

(20 citation statements)

References 71 publications

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“…These observations suggest a less efficient structural organisation of the virome-related microbiome meta-community in asthma, Networks of viral-viral and viral-bacterial co-occurrence were significantly loosened, suggesting that microbial communities may be less resilient in asthma. Viral dysbiosis therefore appears to be not only a key characteristic of asthma pathophysiology, but one that may be amenable to intervention [39][40][41] .…”

Section: Dysbiotic Structure Of the Asthmatic Viromementioning

confidence: 99%

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Megremis

Constantinides

Xepapadaki

et al. 2020

Preprint

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Asthma development and persistence is tightly linked to respiratory viruses. Viral presence is usually interrogated with targeted approaches during periods of disease activity and/or infections, thus neglecting viral occurrence during steady states. We investigate the virome in the upper respiratory system of healthy and asthmatic preschool children during asymptomatic/non-infection periods using metagenomics. Children with asthma have a characteristically dysbiotic virome that correlates to disease severity and control. The major component of dysbiosis is bacteriophage deficiency, while eukaryotic viral presence is increased. At the metacommunity level, differential virus species co-occurrence patterns suggest a decrease of the microbiota community resilience in asthma. Viral dysbiosis is therefore a key characteristic of asthma pathophysiology.

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Section: Dysbiotic Structure Of the Asthmatic Viromementioning

confidence: 99%

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Megremis

Constantinides

Xepapadaki

et al. 2020

Preprint

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“…Effective screening systems are needed. Potaczek and colleagues screened 226 candidate 10-23 DNAzymes targeting human rhinovirus RNA, which resulted in two lead candidates after optimization of binding arm length possessing significant cleavage and antiviral efficacy (21). The recent development of high-throughput kinetic assays may provide a less costly and more efficient way of selecting candidate DNAzyme sequences and mRNA target sites, albeit in single turnover rather than multiple turnover kinetics (22).…”

Section: Further Perspectivesmentioning

confidence: 99%

“…1, 4), rendering the DNAzyme unable to cleave but remaining identical to the test DNAzyme in all other respects (20). Another way is to test for TLR9/NF-kB activation alongside reference oligonucleotides (21). Such "off-target" effects should not be confused with DNAzymes targeting master regulators, such as transcription factors, where that DNAzyme would also be expected to affect other genes reliant on the targeted factor.…”

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confidence: 99%

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Deoxyribozymes as Catalytic Nanotherapeutic Agents

Khachigian

2019

Cancer Research

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RNA-cleaving deoxyribozymes (DNAzymes) are synthetic single-stranded DNA-based catalytic molecules that can be engineered to bind to and cleave target mRNA at predetermined sites. These have been used as therapeutic agents in a range of preclinical cancer models and have entered clinical trials in Europe, China, and Australia. This review surveys regulatory insights into mechanisms of disease brought about by use of catalytic DNA in vitro and in vivo, including recent uses as nanosensors, nanoflowers, and nanosponges, and the emerging role of adaptive immunity underlying DNAzyme inhibition of cancer growth. DNAzymes represent a promising new class of nucleic acid-based therapeutics in cancer. This article discusses mechanistic and therapeutic insights brought about by DNAzyme use as nanotools and reagents in a range of basic science, experimental therapeutic and clinical applications. Current limitations and future perspectives are also discussed.

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“…These DNAzymes have been identified to catalyze many chemical reactions, including RNA cleavage, oxidative or hydrolytic DNA cleavage, DNA/RNA ligation, and DNA phosphorylation [4,5]. These features have been successfully applied in various biomedical applications both in vitro [7][8][9] and in vivo [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

RNA-Cleaving DNAzymes: Old Catalysts with New Tricks for Intracellular and In Vivo Applications

Zhang

2018

Catalysts

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DNAzymes are catalytically active DNA molecules that are normally isolated through in vitro selection methods, among which RNA-cleaving DNAzymes that catalyze the cleavage of a single RNA linkage embedded within a DNA strand are the most studied group of this DNA enzyme family. Recent advances in DNA nanotechnology and engineering have generated many RNA-cleaving DNAzymes with unique recognition and catalytic properties. Over the past decade, numerous RNA-cleaving, DNAzymes-based functional probes have been introduced into many research areas, such as in vitro diagnostics, intracellular imaging, and in vivo therapeutics. This review focus on the fundamental insight into RNA-Cleaving DNAzymes and technical tricks for their intracellular and in vivo applications, highlighting the recent progress in the clinical trial of RNA-Cleaving DNAzymes with selected examples. The challenges and opportunities for the future translation of RNA-cleaving DNAzymes for biomedicine are also discussed.

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Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses

Abstract: Effective and specific management of RV infections with Dua-01-L12R9 might be useful in preventing asthma exacerbations, which should be verified by clinical trials.

Cited by 24 publications

References 71 publications

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Deoxyribozymes as Catalytic Nanotherapeutic Agents

RNA-Cleaving DNAzymes: Old Catalysts with New Tricks for Intracellular and In Vivo Applications

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