DNAzymes: Expanding the Potential of Nucleic Acid Therapeutics

Abstract

Nucleic acids drugs have been proven in the clinic as a powerful modality to treat inherited and acquired diseases. However, key challenges including drug stability, renal clearance, cellular uptake, and movement across biological barriers (foremost the blood–brain barrier) limit the translation and clinical efficacy of nucleic acid–based therapies, both systemically and in the central nervous system. In this study we provide an overview of an emerging class of nucleic acid therapeutic, called DNAzymes. In particular, we review the use of chemical modifications and carrier molecules for the stabilization and/or delivery of DNAzymes in cell and animal models. Although this review focuses on DNAzymes, the strategies described are broadly applicable to most nucleic acid technologies. This review should serve as a general guide for selecting chemical modifications to improve the therapeutic performance of DNAzymes.

Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics

“…The catalytic activity of DNAzyme is highly dependent on the high concentration of DNAzyme cofactors (Figure A,B). Nevertheless, the intracellular Mg 2+ concentration (approximately 0.50 mM) is insufficient to support effective DNAzyme cleavage. , Fittingly, the alternative Mn 2+ also revealed substantially great catalytic efficacy (Figure C,D). The two DNAzymes were annealed with an excess of their corresponding substrate sequence.…”

Multivalent DNAzyme agents for cleaving folded RNA

“…When OGT agents act in the intracellular environment, their concentrations are poorly controlled because of inefficient delivery, poor exosomal escape, and nuclease degradation ( 15 , 16 ). Therefore, OGT agents active at low concentrations are preferable.…”

“…Dz are known to be the most selective OGT agents: no hybridization-dependent off-target activity has been reported for Dz agents so far ( 14 ). Several Dz agents were tested in phase II of clinical trials ( 15–17 ).…”

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

“…Dzs are single-stranded DNA molecules with catalytic functions that provide perspectives in the diagnosis and therapy of diseases. 9–11 Their chemical stability, cost-effective synthesis, and compatibility with biological systems make them superior to traditional hybridization probes. DNAzymes excel in structural predictability and modification, allowing the development of cost-efficient detection assays free from reliance on expensive proteins.…”