RNA‐Cleaving DNAzyme‐Based Amplification Strategies for Biosensing and Therapy

Abstract

Since their first discovery in 1994, DNAzymes have been extensively applied in biosensing and therapy that act as recognition elements and signal generators with the outstanding properties of good stability, simple synthesis, and high sensitivity. One subset, RNA‐cleaving DNAzymes, is widely employed for diverse applications, including as reporters capable of transmitting detectable signals. In this review, the recent advances of RNA‐cleaving DNAzyme‐based amplification strategies in scaled‐up biosensing are focused, the application in diagnosis and disease treatment are also discussed. Two major types of RNA‐cleaving DNAzyme‐based amplification strategies are highlighted, namely direct response amplification strategies and combinational response amplification strategies. The direct response amplification strategies refer to those based on novel designed single‐stranded DNAzyme, and the combinational response amplification strategies mainly include two‐part assembled DNAzyme, cascade reactions, CHA/HCR/RCA, DNA walker, CRISPR‐Cas12a and aptamer. Finally, the current status of DNAzymes, the challenges, and the prospects of DNAzyme‐based biosensors are presented.

Tunable metal–organic frameworks assist in catalyzing DNAzymes with amplification platforms for biomedical applications

“…14,15 Currently, numerous Dzs are being developed through the SELEX strategy, such as Dzs for RNA sequence-specific cutting and RNA-cutting Dzs for detection of breast cancer cells. With the accomplishments of the SELEX strategy based on the enormous potential of Dzs in molecular sensing detection, 7,15,16 cell imaging, 8,14,17 cancer treatment [18][19][20] and more, Dzs will likely find applications in more fields.…”

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

“…5,6 However, compared to DNA gene therapeutic agents, RNA is less stable and exhibits lower enzymatic degradation resistance. 7 Finding stable DNA gene therapeutic agents with the same function as siRNA is thus critical to resolving the above issues. 8 DNAzymes with RNA cleavage ability have garnered a great deal of attention in recent years.…”

“…Studies have shown that B-cell lymphoma 2 (Bcl-2) and Survivin (Svv) mRNAs are overexpressed in RB cells, suggesting that these two mRNAs might be promising therapeutic targets. , In particular, the eye offers certain anatomical advantages as a target tissue, which is conducive to the development of multifunctional diagnostic nanocontrast agents combining anti-RB gene therapeutic agents with multimodal imaging technology. Currently, the agents mainly used for RB gene therapy are small interfering RNA (siRNA). , However, compared to DNA gene therapeutic agents, RNA is less stable and exhibits lower enzymatic degradation resistance . Finding stable DNA gene therapeutic agents with the same function as siRNA is thus critical to resolving the above issues .…”

Bioorthogonal Activation of RCA-Based Amplifiable DNAzymes in Bimetallic NMOF for Precise Gene/Chemo-Dynamic Combination Therapy

“…In the era of precision cancer therapy, precise initiation and efficient treatment are crucial issues to ensure satisfactory efficacy, which remains challenging in biomedicine. , Gene therapy, which can modulate disease-related proteins to continuously inhibit tumor proliferation and metastasis at the root, is considered the ultimate panacea for cancer treatment. , Among various gene drugs such as antisense oligonucleotides (ASOs), small interfering RNA (siRNA), , and clustered regularly interspersed short palindromic repeats (CRISPRs), , etc. , DNAzyme has received special attention owing to its flexible design and enzyme-like activity, which enables it to specifically recognize and continuously cleave target genes. − However, the current DNAzyme-based gene therapy faces several limitations: (a) low transfection efficiency and insufficient cofactor supply, , (b) poor specificity causing adverse reactions, , and (c) inadequate effects of monotherapy. − …”