The Evolution of Nucleic Acid Nanotechnology: From DNA Assembly to DNA‐Encoded Library

Deoxyribonucleic acid (DNA), a fundamental biomacromolecule in living organisms, serves as the carrier of genetic information. Beyond its role in encoding biological functions, DNA's inherent ability to hybridize through base pairing has opened new avenues for its application in biological sciences. This review introduces DNA nanotechnology and DNA-encoded library (DEL), and highlights their shared design principles related to DNA assembly. First, a foundational overview of structural DNA nanotechnology, including its design strategies and historical development is provided. Subsequently, various approaches are examined to dynamic DNA nanotechnology, from strand displacement reactions to DNA-templated polymer synthesis. Second, how the principle of DNA assembly has facilitated the development of diverse formats of self-assembly-based DEL synthesis, DNA-template reactions (DTS), and DNA template-mediated proximity induction effects are examined. These advancements are all underpinned by the unique property of DNA assembly. Finally, this review summarizes the common principles shared by DNA nanotechnology and DEL in terms of methodology and design. Additionally, the potential synergies are explored between these two technologies, envisioning future applications where they can be combined to create more versatile and exquisite functionalities.