# 3D DNA Nanostructures: The Nanoscale Architect
###### Abstract  
Structural DNA nanotechnology is a pioneering biotechnology that presents the opportunity to engineer DNA-based hardware that will mediate a profound interface to the nanoscale. To date, an enormous library of shaped 3D DNA nanostructures have been designed and assembled. Moreover, recent research has demonstrated DNA nanostructures that are not only static but can exhibit specific dynamic motion. DNA nanostructures have thus garnered significant research interest as a template for pursuing shape and motion-dependent nanoscale phenomena. Potential applications have been explored in many interdisciplinary areas spanning medicine, biosensing, nanofabrication, plasmonics, single-molecule chemistry, and facilitating biophysical studies. In this review, we begin with a brief overview of general and versatile design techniques for 3D DNA nanostructures as well as some techniques and studies that have focused on improving the stability of DNA nanostructures in diverse environments, which is pivotal for its reliable utilization in downstream applications. Our main focus will be to compile a wide body of existing research on applications of 3D DNA nanostructures that demonstrably rely on the versatility of their mechanical design. Furthermore, we frame reviewed applications into three primary categories, namely encapsulation, surface templating, and nanomechanics, that we propose to be archetypal shape- or motion-related functions of DNA nanostructures found in nanoscience applications. Our intent is to identify core concepts that may define and motivate specific directions of progress in this field as we conclude the review with some perspectives on the future. structural DNA nanotechnology; DNA origami; DNA-template synthesis; nanomechanics; drug delivery; nanofabrication +
Footnote †: 2021: 11, 2624. [[https://doi.org/10.3390/app1106264](https://doi.org/10.3390/app1106264)]([https://doi.org/10.3390/app1106264](https://doi.org/10.3390/app1106264))
its simplicity and functional generality; prescriptive design of the Watson-Crick bonding reactions of only DNA reagents yields a vast complexity of computational and structural architectures. Furthermore, DNA is biocompatible, soluble, and its chemistry is amenable to the attachment of functional groups consisting of various other organic and inorganic materials. The prospect of free-form structural self-assembly is enticing, and fundamentals of geometric design in DNA nanotechnology have also inspired the same principles to be investigated for RNA [4] or proteins [5; 6] as the base material. **Organization of Review:** This review focuses on structural DNA nanotechnology, that is, the subfield concerned with the design and operation of self-assembled nanoparticles composed primarily of DNA, or _DNA nanostructures_. The goal of the review is to corroborate the significance of the exact mechanical design of DNA nanostructures and their properties, such as shape, stiffness, elasticity, and actuation, towards deliberate physical control of nanoscale phenomena. This review will first recall various techniques that exist for designing static 3D DNA nanostructures for specific geometric categories, and we stress the importance of software packages for their design and simulation. We will also discuss emerging techniques for composing static components into dynamic mechanical assemblies. Next, we summarize several studies on the stability of DNA nanostructures that, in practice, is necessary knowledge to reliably utilize the aforementioned DNA nanostructures in their downstream applications. Finally, we devote a significant portion of this review on the discussion of applications, divided into three categories, namely encapsulation, surface templating, and nanomechanics, and we propose that each identifies a common, archetypal function of 3D DNA nanostructures present in nanoscience applications (Figure 1).