Designer 3D-DNA nanodevices: Structures, functions, and cellular applications

The field of DNA nanotechnology has diverged into various areas of applications ranging from computing, photonics, biosensing to in vivo bioimaging and therapeutic delivery, to name a few. In the beginning, most of the work was focused on the structural aspects of DNA nanotechnology involving designing structurally complex structures using DNA as a structural component. More recently, the focus has been diverted into biologically oriented DNA nanotechnology, which seeks to explore the functionalities of combinatorial DNA devices in various biological systems. DNA nanocages realized till date have proven to be versatile structures owing to their inherent biocompatibility and chemical flexibility that allows ease of functionalization with different biological or chemical moieties, high programmability, and high stability, leading to enhanced biological uptake and targeting as compared to similar other biological scaffolds like proteins, lipids, carbohydrates, synthetic polymers, etc. Owing to these properties, TDNs exhibits optimistic potential for different biomedical applications leading to their clinical applications. In this chapter, we discuss different classes of 3D DNA nanodevices and the methods for synthesizing DNA nanostructures. We further discuss different techniques to characterize them in bulk and at single-molecule resolution, followed by the protocol for their cellular uptake and imaging. We finally conclude with a short perspective on future modifications of DNA nanodevices to maximize their potential for biomedical and clinical applications.