Recent advances of DNAzyme-based nanotherapeutic platform in cancer gene therapy

Huo, Wendi; Li, Xiaona; Wang, Bei; Zhang, Haoran; Zhang, Jinchao; Yang, Xinjian; Jin, Y.

doi:10.1007/s41048-020-00123-w

Cited by 27 publications

(24 citation statements)

References 58 publications

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“…Currently, DNAzymes are not found in nature but are generated using in vitro selection strategies (SELEX) [ 83 ]. DNAzymes that cleave RNAs are the most well studied type of DNAzymes in cancer research due to their potential to silence genes [ 84 ]. 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 ].…”

Section: Types Of Oligonucleotide Therapeuticsmentioning

confidence: 99%

“…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 ]. DNAzymes also face the challenge of nuclease degradation.…”

Section: Types Of Oligonucleotide Therapeuticsmentioning

confidence: 99%

“…Efficient cellular delivery is another barrier for the application of DNAzymes and nanocarriers such as lipid nanoparticles and cationic polymers can improve uptake [ 88 ]. Despite promising outcomes in vitro and in animal models, only one clinical trial has been completed for DNAzymes in oncology thus far [ 84 ].…”

Section: Types Of Oligonucleotide Therapeuticsmentioning

confidence: 99%

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Recent Advances in Oligonucleotide Therapeutics in Oncology

Xiong

Veedu

Diermeier

2021

IJMS

119

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%

Section: Types Of Oligonucleotide Therapeuticsmentioning

confidence: 99%

Section: Types Of Oligonucleotide Therapeuticsmentioning

confidence: 99%

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Recent Advances in Oligonucleotide Therapeutics in Oncology

Xiong

Veedu

Diermeier

2021

IJMS

119

103

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“…Since then, several DNAzymes have been synthesized, targeting various genes leading to cancer onset and progression [9]. Mainly, RNA-cleaving DNAzymes have been broadly investigated due to their potential to downregulate the target protein by cleaving corresponding mRNA [11]. Although DNAzymes possess high stability and selectivity than ribozymes, the therapeutic applications are limited by the inept delivery to intracellular targets [4].…”

Section: Introductionmentioning

confidence: 99%

DNAzymes, Novel Therapeutic Agents in Cancer Therapy: A Review of Concepts to Applications

Thomas

Gaminda

Jayasinghe

et al. 2021

Journal of Nucleic Acids

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The past few decades have witnessed a rapid evolution in cancer drug research which is aimed at developing active biological interventions to regulate cancer-specific molecular targets. Nucleic acid-based therapeutics, including ribozymes, antisense oligonucleotides, small interference RNA (siRNA), aptamer, and DNAzymes, have emerged as promising candidates regulating cancer-specific genes at either the transcriptional or posttranscriptional level. Gene-specific catalytic DNA molecules, or DNAzymes, have shown promise as a therapeutic intervention against cancer in various in vitro and in vivo models, expediting towards clinical applications. DNAzymes are single-stranded catalytic DNA that has not been observed in nature, and they are synthesized through in vitro selection processes from a large pool of random DNA libraries. The intrinsic properties of DNAzymes like small molecular weight, higher stability, excellent programmability, diversity, and low cost have brought them to the forefront of the nucleic acid-based therapeutic arsenal available for cancers. In recent years, considerable efforts have been undertaken to assess a variety of DNAzymes against different cancers. However, their therapeutic application is constrained by the low delivery efficiency, cellular uptake, and target detection within the tumour microenvironment. Thus, there is a pursuit to identify efficient delivery methods in vivo before the full potential of DNAzymes in cancer therapy is realized. In this light, a review of the recent advances in the use of DNAzymes against cancers in preclinical and clinical settings is valuable to understand its potential as effective cancer therapy. We have thus sought to firstly provide a brief overview of construction and recent improvements in the design of DNAzymes. Secondly, this review stipulates the efficacy, safety, and tolerability of DNAzymes developed against major hallmarks of cancers tested in preclinical and clinical settings. Lastly, the recent advances in DNAzyme delivery systems along with the challenges and prospects for the clinical application of DNAzymes as cancer therapy are also discussed.

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“…Comparing with traditional siRNA-based gene silencing strategy, cAD holds high stability in vivo and can be spontaneously uptaken by tumor cells, due to the circular structure and functional aptamer sequence 17 . Besides, DNAzyme are catalytic nucleic acids that can mimic the function of endonucleases for cleavage of speci c mRNA with multiple turnovers, which may be more effective for PD-L1 gene silencing on a per molecule basis 18,19 . However, DNAzymes always need su cient ion cofactor supply for activation, which just can be solved by our "Ca 2+ interference" strategy 20,21 .…”

Section: Introductionmentioning

confidence: 99%

Bioactive nanoparticles for boosting tumor immunotherapy via Ca2+ interference mediate TME reprogramming and PD-L1 depletion

Shi¹,

An²,

Zhang³

et al. 2021

Preprint

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The efficacy of antitumor immunotherapy is often limited by the highly tumor immunosuppressive microenvironment (TME). Here, a previously unknown strategy is proposed to synergize the “Ca2+ interference” mediate TME reprogramming and Ca2+-activating PD-L1 depletion for immunotherapy. We discovered that calcium containing nanoparticles could induce significant “Ca2+ interference” effect and simultaneously resetting tumor-associated macrophages toward M1 phenotype and promoting in situ antigen release. Making them as powerful immunostimulants for TME reprogramming without notable toxicity. Meanwhile, we designed a circular aptamer-DNAzyme conjugate (cAD) with tumor-targeting ability and its catalytic shear activity can be specifically activated by Ca2+, which reduces potential autoimmune disorders of PD-L1 antibody. By simple integrating the ultra-high pH sensitive calcium peroxide nanoparticles with cAD into one nanosystem, we demonstrate the nanosystem not only arrests primary tumor progression, but also prevents lung metastasis. In addition, it offers a long-term immunological memory function, which can protect against tumor rechallenge. Therefore, this work provided an alternative strategy for boosting tumor immunotherapy.

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Recent advances of DNAzyme-based nanotherapeutic platform in cancer gene therapy

Cited by 27 publications

References 58 publications

Recent Advances in Oligonucleotide Therapeutics in Oncology

Recent Advances in Oligonucleotide Therapeutics in Oncology

DNAzymes, Novel Therapeutic Agents in Cancer Therapy: A Review of Concepts to Applications

Bioactive nanoparticles for boosting tumor immunotherapy via Ca2+ interference mediate TME reprogramming and PD-L1 depletion

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