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RNA-cleaving DNAzymes as a diagnostic and therapeutic agent against antimicrobial resistant bacteria

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Abstract

The development of nucleic-acid-based antimicrobials such as RNA-cleaving DNAzyme (RCD), a short catalytically active nucleic acid, is a promising alternative to the current antibiotics. The current rapid spread of antimicrobial resistance (AMR) in bacteria renders some antibiotics useless against bacterial infection, thus creating the need for alternative antimicrobials such as DNAzymes. This review summarizes recent advances in the use of RCD as a diagnostic and therapeutic agent against AMR. Firstly, the recent diagnostic application of RCD for the detection of bacterial cells and the associated resistant gene(s) is discussed. The next section summarises the therapeutic application of RCD in AMR bacterial infections which includes direct targeting of the resistant genes and indirect targeting of AMR-associated genes. Finally, this review extends the discussion to challenges of utilizing RCD in real-life applications, and the potential of combining both diagnostic and therapeutic applications of RCD into a single agent as a theranostic agent.

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Abbreviations

AMR:

Antimicrobial resistance

ASO:

Antisense oligonucleotides

CEM:

Crude extracellular matrix

CR:

Carbapenem-resistant

ESBL:

Extended-spectrum beta-lactamases

F/Q:

Fluorophore/quencher

G4:

G-quadruplexes

MDR:

Multidrug-resistant

MNAzyme:

Multicomponent nucleic acid enzyme

MRSA:

Methicillin-resistant Staphylococcus aureus

NGS:

Next generation sequencing

PCR:

Polymerase chain reaction

RCD:

RNA-cleaving DNAzyme

RFD:

RNA-cleaving fluorescent DNAzymes

SELEX:

Systematic evolution of ligands by exponential enrichment

SNPs:

Single nucleotide polymorphisms

VRE:

Vancomycin-resistant enterococci

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Funding

This work was supported by the Tropical Medicine and Biology Multidisciplinary Platform and School of Science, Monash University Malaysia.

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Authors

Contributions

WBC, JAB and AD wrote the manuscript. HST conceptualize the paper, supervised the project and reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hock Siew Tan.

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The authors have no competing interests to declare.

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Not applicable.

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Communicated by Michael Polymenis.

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Wong, B.C., Abu Bakar, J., Dhanoa, A. et al. RNA-cleaving DNAzymes as a diagnostic and therapeutic agent against antimicrobial resistant bacteria. Curr Genet 68, 27–38 (2022). https://doi.org/10.1007/s00294-021-01212-0

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  • DOI: https://doi.org/10.1007/s00294-021-01212-0

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