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

Abstract

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.

Gene and Photothermal Combination Therapy: Principle, Materials, and Amplified Anticancer Intervention

“…[ 99 ] As an emerging nucleic acid‐based therapeutic agent against cancer, DNAzymes offer several advantages such as small molecular weight, good serum stability, high specificity and reactivity, and low cost. [ 100 ] Although DNAzymes are primarily used to silence genes involved in cell proliferation, migration, and carcinogenesis, [ 101 ] they can also be utilized to disrupt HSP production for mild‐temperature PTT.…”

Towards the development of a DNA automaton: modular RNA-cleaving deoxyribozyme logic gates regulated by miRNAs

“…The catalytic capabilities of deoxyribozymes (Dzs) enable them to perform specific reactions under controlled conditions, making them ideal candidates for targeted gene regulation. 7,8 By harnessing the power of DNA computation, therapeutic interventions can be tailored to individual genetic profiles, ushering in an era of personalized medicine with enhanced efficacy and reduced side effects. Dzs are single-stranded DNA molecules with catalytic functions that provide perspectives in the diagnosis and therapy of diseases.…”

The recent advancements in the early detection of cancer biomarkers by DNAzyme-assisted aptasensors

“…DNAzyme contains a central catalytic zone that is surrounded by two-sided recognition arms. The longer recognizing more robust arm binds to its substrate via DNAzyme’s Watson-Crick base-pairing [ 20 ]. In this approach, the unique sequence of recognition arms defines the specificity of the DNAzyme and stabilizes the DNAzyme’s catalytic core, allowing the hydrolysis event to take place [ 17 , 19 ].…”

“…In this approach, the unique sequence of recognition arms defines the specificity of the DNAzyme and stabilizes the DNAzyme’s catalytic core, allowing the hydrolysis event to take place [ 17 , 19 ]. The most common forms of DNAzyme are 8–17 and 10–23 DNAzyme, which may break practically any phosphodiester link between unpaired purines and paired pyrimidines [ 20 , 21 ]. DNAzyme may successfully cut off the target mRNA in the presence of particular metal ions including Mg 2+ , Pb 2+ , Mn 2+ , Cu 2+ , and Na + by catalyzing the hydrolysis of the target RNA’s phosphodiester [ 20 , 22 ].…”

“…The most common forms of DNAzyme are 8–17 and 10–23 DNAzyme, which may break practically any phosphodiester link between unpaired purines and paired pyrimidines [ 20 , 21 ]. DNAzyme may successfully cut off the target mRNA in the presence of particular metal ions including Mg 2+ , Pb 2+ , Mn 2+ , Cu 2+ , and Na + by catalyzing the hydrolysis of the target RNA’s phosphodiester [ 20 , 22 ]. Therefore, DNAzyme might become a promising revolutionary gene therapy strategy and a powerful tool for the fabrication of biosensing platforms for cancer diagnosis.…”