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

Zhang, Jing Jing

doi:10.3390/catal8110550

Cited by 42 publications

(31 citation statements)

References 106 publications

(133 reference statements)

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“…These RNA-cleavage DNAzymes consist of a catalytic core and two arms, which bind and recognize specific RNA sequence through Watson–Crick base pairing [ 85 ]. Two widely studied DNAzymes are 10-23 DNAzymes and 8-17 DNAzymes [ 86 ]. The efficiency of the RNA cleavage relies on the metal ion in the core [ 84 ].…”

Section: Types Of Oligonucleotide Therapeuticsmentioning

confidence: 99%

Recent Advances in Oligonucleotide Therapeutics in Oncology

Xiong

Veedu

Diermeier

2021

IJMS

129

103

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Cancer is one of the leading causes of death worldwide. Conventional therapies, including surgery, radiation, and chemotherapy have achieved increased survival rates for many types of cancer over the past decades. However, cancer recurrence and/or metastasis to distant organs remain major challenges, resulting in a large, unmet clinical need. Oligonucleotide therapeutics, which include antisense oligonucleotides, small interfering RNAs, and aptamers, show promising clinical outcomes for disease indications such as Duchenne muscular dystrophy, familial amyloid neuropathies, and macular degeneration. While no approved oligonucleotide drug currently exists for any type of cancer, results obtained in preclinical studies and clinical trials are encouraging. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in oncology, review current clinical trials, and discuss associated challenges.

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Section: Types Of Oligonucleotide Therapeuticsmentioning

confidence: 99%

Recent Advances in Oligonucleotide Therapeutics in Oncology

Xiong

Veedu

Diermeier

2021

IJMS

129

103

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“…Despite these advantages, their instability in biological media, targeted delivery and low efficiency of cellular uptake remain the major challenges for employing DNAzymes as potent therapeutics. [14][15][16][17] The hydrophobic nature of cell membranes prevents the highly hydrophilic DNAzymes from crossing the membranes to enter cells. Efforts using cationic molecules, 18 nanomaterials [19][20][21][22][23][24] and liposomes 25,26 as carriers to ferry DNAzymes into cells have been extensively reported.…”

Section: Introductionmentioning

confidence: 99%

Targeted and direct intracellular delivery of native DNAzymes enables highly specific gene silencing

Yang

Zhou

et al. 2020

Chem. Sci.

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“…Among these FNA‐based nanosystems, the functions of FNAs can be categorized into two types: diagnostic function and therapeutic function. For the diagnostic function, the FNAs serve either as the biorecognition ligands for direct sensing and imaging of the specific targets, or as the biocatalysts to produce signal amplification for indirect sensing and imaging of other targets of interest . On the other hand, for the therapeutic function, the FNAs could be directly used as the therapeutic drugs for some diseases or serve as the host of other therapeutic reagents, including anticancer drugs, miRNAs, and siRNAs.…”

Section: Introductionmentioning

confidence: 99%

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

Zhang

Lan

2019

Adv Healthcare Materials

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equally exciting and perhaps more challenging field of application is toward their in vivo applications, including living animals and human bodies, in diverse areas, [2] such as sensing, drug delivery, medical imaging, and cancer therapy. However, most of these nanomaterials lack selectivity toward targets of interests. Therefore, to employ these nanomaterials for a wider range of in vivo applications, various molecular engineering approaches have been employed to obtained nanomaterials functionalized with biomolecules to enable selective targeting. [3][4][5] Among these biomolecules, functional nucleic acids, or FNAs, have shown the most promise.FNAs are DNA or RNA molecules that can interact with or bind to a specific analyte, resulting in a conformational change and/or a catalytic reaction. [6] As their names suggested, ribozymes and deoxyribozymes (called DNAzyme hereafter) can act as enzymes in the presence of cofactors to catalyze various reactions, including cleavage and ligation of RNA/DNA, and phosphorylation and peroxidation of DNA. On the other hand, riboswitches and DNA aptamers are antibody-like receptors that can bind target molecules with high affinity and selectivity. Furthermore, the binding abilities of riboswitches and aptamers can be combined with the enzymatic function of ribozymes or DNAzymes to form aptazymes so that the binding of targets can inhibit or enhance the catalytic activities. These nucleic acids, including DNAzymes, aptamers, and aptazymes, are collectively known as FNAs to emphasize their functions beyond the traditional genetic storage and transformations roles for DNA and RNA. Unlike DNA and RNA inside biological systems, FNAs are isolated via a combinatorial technique known as in vitro selection, or a process also known as systematic evolution of ligands by exponential enrichment (SELEX). The discovery of new functions of nucleic acids has not only resulted in major advances in the fields of molecular biology and biochemistry, but also revolutionized sensors designs for both in vitro and in vivo applications. [7,8] Over the past decade, numerous FNA-based nanomaterials have been developed. [9][10][11][12] Among these FNA-based nanosystems, the functions of FNAs can be categorized into two types: diagnostic function and therapeutic function. For the diagnostic function, the FNAs serve either as the biorecognition ligands for direct sensing and imaging of the Recent advances in nanotechnology and engineering have generated many nanomaterials with unique physical and chemical properties. Over the past decade, numerous nanomaterials are introduced into many research areas, such as sensors for environmental monitoring, food safety, point-ofcare diagnostics, and as transducers for solar energy transfer. Meanwhile, functional nucleic acids (FNAs), including nucleic acid enzymes, aptamers, and aptazymes, have attracted major attention from the biomedical community due to their unique target recognition and catalytic properties. Benefiting from the recent progress of molecular engine...

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

Cited by 42 publications

References 106 publications

Recent Advances in Oligonucleotide Therapeutics in Oncology

Recent Advances in Oligonucleotide Therapeutics in Oncology

Targeted and direct intracellular delivery of native DNAzymes enables highly specific gene silencing

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

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