Molecular micromanagement: DNA nanotechnology establishes spatio-temporal control for precision medicine

Current advances in DNA nanotechnology pinpoint exciting perspectives for the design of customized, patient-specific treatments. This advance is made possible by the exceptionally high precision and specificity that are typical for DNA base pairing on the one hand and our growing ability to harness those features in synthetic, DNA-based constructs on the other hand. Modern medicine may soon benefit from recent developments in this field, especially regarding the targeted delivery of drugs and the rational interference of synthetic DNA strands with cellular oligonucleotides. In this Review, we summarize selected examples from the area of DNA nanotechnology, where the development of precisely controlled, advanced functional mechanisms was achieved. To demonstrate the high versatility of these rationally designed structures, we categorize the dynamic DNA-based materials suggested for precision medicine according to four fundamental tasks: "hold & release," "heal," "detect & measure," as well as "guide & direct." In all the biomedical applications we highlight, DNA strands not only constitute structural building blocks but allow for creating stimuli-responsive objects, serve as an active cargo, or act as molecular control/guidance tools. Moreover, we discuss several issues that need to be considered when DNA-based structures are designed for applications in the field of precision medicine. Even though the majority of DNA-based objects have not been used in clinical settings yet, recent progress regarding the stability, specificity, and control over the dynamic behavior of synthetic DNA structures has advanced greatly. Thus, medical applications of those nanoscopic objects should be feasible in the near future.