Exploring the Potential of Three‐Dimensional DNA Crystals in Nanotechnology: Design, Optimization, and Applications

Abstract

DNA has been used as a robust material for the building of a variety of nanoscale structures and devices owing to its unique properties. Structural DNA nanotechnology has reported a wide range of applications including computing, photonics, synthetic biology, biosensing, bioimaging, and therapeutic delivery, among others. Nevertheless, the foundational goal of structural DNA nanotechnology is exploiting DNA molecules to build three‐dimensional crystals as periodic molecular scaffolds to precisely align, obtain, or collect desired guest molecules. Over the past 30 years, a series of 3D DNA crystals have been rationally designed and developed. This review aims to showcase various 3D DNA crystals, their design, optimization, applications, and the crystallization conditions utilized. Additionally, the history of nucleic acid crystallography and potential future directions for 3D DNA crystals in the era of nanotechnology are discussed.

Controlling the Crystal Growth of DNA Molecules via Strategic Chemical Modifications

“…Further, the new insights into the strength of these interactions provide versatile tools for fine‐tuning crystallization behaviour and controlling crystal morphology. Last but not least, our discovery opens up a promising avenue for controling the self‐assembly of structural DNA nanotechnology [16] . In detail, the 2’‐O‐methylation of DNA can expedite self‐assembly kinetics, whereas PS modification leads to slower self‐assembly kinetics compared to unmodified DNA.…”

“…Last but not least, our discovery opens up a promising avenue for controling the selfassembly of structural DNA nanotechnology. [16] In detail, the 2'-O-methylation of DNA can expedite self-assembly kinetics, whereas PS modification leads to slower self-assembly kinetics compared to unmodified DNA. Therefore, the hierarchical and preferential assembly in the design of DNA nanostructures can be achieved through these strategic chemical modifications.…”

Importance of DNA nanotechnology for DNA methyltransferases in biosensing assays

“…Their high stability ensures the reliability and durability of the DNA nanostructures for various biomedical applications (Table 1). Thus, the rapid development of DNA nanotechnology has led to a wide range of applications of DNA nanomaterials in biomedical fields, including sensing, 66 diagnostics, therapeutics, and imaging, as functional carriers for drug delivery and nucleic acid detection. 67 In diagnostics, DNA nanomaterials provide a platform for detecting highly specific biomarkers.…”

Tuning Chemical DNA Ligation within DNA Crystals and Protein–DNA Cocrystals

“…Crystals made from protein and DNA are versatile materials that precisely order molecules, self-assemble, and have tunable growth. − Porous crystals have been shown to act as molecular sieves − and to host molecules for structure determination, − enhance enzymatic activity, , and information storage via synthetic DNA sequences . Engineered crystals with DNA building blocks, from pure DNA crystals , to hybrid protein–DNA crystals, have been designed to serve as scaffolds for DNA-binding molecules. − However, the broad utility of crystals held together by DNA is restricted by their ability to survive in varied solution conditions.…”