Importance of DNA nanotechnology for DNA methyltransferases in biosensing assays.

DNA methylation is the process by which specific bases on a DNA sequence acquire methyl groups under the catalytic action of DNA methyltransferases (DNMT). Abnormal changes in the function of DNMT are important markers for cancers and other diseases; therefore, the detection of DNMT and the selection of its inhibitors are critical to biomedical research and clinical practice. DNA molecules can undergo intermolecular assembly to produce functional aggregates because of their inherently stable physical and chemical properties and unique structures. Conventional DNMT detection methods are cumbersome and complicated processes; therefore, it is necessary to develop biosensing technology based on the assembly of DNA nanostructures to achieve rapid analysis, simple operation, and high sensitivity. The design of the relevant program has been employed in life science, anticancer drug screening, and clinical diagnostics. In this review, we explore how DNA assembly, including 2D techniques like hybridization chain reaction (HCR), rolling circle amplification (RCA), catalytic hairpin assembly (CHA), and exponential isothermal amplified strand displacement reaction (EXPAR), as well as 3D structures such as DNA tetrahedra, G-quadruplexes, DNA hydrogels, and DNA origami, enhances DNMT detection. We highlight the benefits of these DNA nanostructure-based biosensing technologies for clinical use and critically examine the challenges of standardizing these methods. We aim to provide reference values for the application of these techniques in DNMT analysis and early cancer diagnosis and treatment, and to alert researchers to challenges in clinical application.