Designer DNA‐Based Machines

ABSTRACT Designer DNA‐based machines represent a rapidly emerging interdisciplinary field at the intersection of bionanotechnology, mechanical engineering, and computer science and has garnered increasing attentions from both academia and industry due to their transformative potential in various applications. In this article, we review the research of DNA‐based machines, covering design, analysis, fabrication, biomedical applications, and roles in nanomanufacturing; for the future developments, we further provide perspectives across the entire pipeline from design to actuation in terms of interdisciplinary and AI empowerment. We first outline the foundational principles of DNA self‐assembly and trace the evolution of DNA‐based machines from static motifs to dynamic robots. We then critically explore the integration of mechanical design into DNA nanotechnology for engineering kinematic joints, rigid‐body, and compliant mechanisms—critical components that enable the rational construction of increasingly complex DNA machines. Thirdly, we evaluate available design and analysis tools, highlighting the shift from shape‐based to motion‐based design and the critical trade‐off between multiscale simulation accuracy and computational efficiency. We also assess the laboratory‐scale fabrication methods and biomanufacturing strategies. Finally, we highlight diverse applications of DNA‐based machines, while offering future directions, including AI‐enhanced intelligent design, predictable mechanical characterization, and the transition toward autonomous, industrial‐scale fabrication. The in‐depth integration of DNA‐based machines with mechanical science, robotics, and artificial intelligence is poised to propel their evolution and expand their transformative roles in advancing precision medicine, atomic‐scale manufacturing, and information‐bionanotechnology convergence.