Engineered 3D DNA Crystals: A Molecular Design Perspective

Abstract Recent advances in biomolecular self‐assembly have transformed material science, enabling the creation of novel materials with unparalleled precision and functionality. Among these innovations, 3D DNA crystals have emerged as a distinctive class of macroscopic materials, engineered through the bottom‐up approach by DNA self‐assembly. These structures uniquely combine precise molecular ordering with high programmability, establishing their importance in advanced material design. This review delves into the molecular design of engineered 3D DNA crystals, classifying current crystal structures based on “crystal bond orientations” and examining key aspects of in‐silico molecular design, self‐assembly, and crystal modifications. The functionalization of 3D DNA crystals for applications in crystallization scaffolding, biocatalysis, biosensing, electrical and optical devices, as well as in the emerging fields of DNA computing and data storage are explored. Finally, the ongoing challenges are addressed and future directions to advance the field of engineered 3D DNA crystals are proposed.