DNAzymes have been recognized as potent therapeutic agents for gene therapy, while their inefficient intracellular delivery and insufficient cofactor supply precludes their practical biological applications.M etal-organic frameworks (MOFs) have emerged as promising drug carriers without in-depth consideration of their disassembled ingredients.Herein, we report aself-sufficient MOF-based chlorin e6modified DNAzyme (Ce6-DNAzyme) therapeutic nanosystem for combined gene therapyand photodynamic therapy(PDT). The ZIF-8 nanoparticles (NPs) could efficiently deliver the therapeutic DNAzyme without degradation into cancer cells. The pH-responsive ZIF-8 NPs disassemble with the concomitant release of the guest DNAzyme payloads and the host Zn 2+ ions that serve,respectively,asmessenger RNA-targeting agent and required DNAzyme cofactors for activating gene therapy. The auxiliary photosensitizer Ce6 could produce reactive oxygen species (ROS) and provide afluorescence signal for the imaging-guided gene therapy/PDT.
G-quadruplex (G4) is an important type of nucleic acid secondary structure. An abundance of potential G4-forming sites have been shown to exist in genomes, leading to increasing interest in this research field. G4 motifs are thought to be involved in the regulation of diverse biological processes and to interact with various protein factors. Because of their important regulatory functions, G4s could have a variety of applications, the most meaningful of which is the role of G4s as potential targets of antitumor therapies. Here, we focus on the regulatory functions of G4s in tumor-related gene regulation and the use of G4s in the design of antitumor therapies, including relatively recently reported G4-related binding proteins, regulatory mechanisms, and G4-ligand designs. We also introduce G4 probes for the identification of G4 structure formation in live cells. Finally, we describe some challenges in this field and the new G4-related research field.
The epigenetic modification of nucleic acids represents one of the most significant areas of study in the field of nucleic acids because it makes gene regulation more complex and heredity more complicated, thus indicating its profound impact on aspects of heredity, growth, and diseases. The recent characterization of epigenetic modifications of DNA and RNA using chemical labelling strategies has promoted the discovery of these modifications, and the newly developed single-base or single-cell resolution mapping strategies have enabled large-scale epigenetic studies in eukaryotes. Due to these technological breakthroughs, several new epigenetic marks have been discovered that have greatly extended the scope and impact of epigenetic modifications in nucleic acids over the past few years. Because epigenetics is reversible and susceptible to environmental factors, it could potentially be a promising direction for clinical medicine research. In this review, we have comprehensively discussed how these epigenetic marks are involved in disease, including the pathogenesis, prevention, diagnosis and treatment of disease. These findings have revealed that the epigenetic modification of nucleic acids has considerable significance in various areas from methodology to clinical medicine and even in biomedical applications.
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