Controlled assembly of exogenous DNA-based materials in living cells

The self-assembly of artificial structures within living cells provides valuable insights into cellular mechanisms and control of cellular functions, thereby contributing to advancements in biomedicine and synthetic biology. To precisely control the intracellular assembly process, exogenous active substances have been introduced, which respond to the natural intracellular environments. Deoxyribonucleic acid (DNA) is a versatile biological macromolecule that has great potential as a building block to construct biomaterials in addition to as a genetic material. Through rational sequence design, DNA molecules can form a variety of functional structures, enabling precise and efficient intracellular assembly. These properties greatly enrich the forms of intracellular assembly and expand the applications of DNA molecules. In this review, we summarize the controlled assembly of exogenous DNA-based materials under various stimulating conditions. We highlight three main applications of intracellular assembly of exogenous DNA materials. First, DNA materials interact with intracellular molecules to alter the natural intracellular environment and influence cell behavior and fate. Second, DNA materials form assemblies that affect subcellular structures and interfere with cellular functions. Third, DNA functional modules enable precise diagnosis and treatment of cancers by recognizing intracellular molecules for efficient tumor detection, precise imaging, and controlled drug delivery. From assembly mechanisms to biological effects, this review comprehensively summarizes the dynamic and controlled assembly of exogenous DNA-based materials in living cells and envisages the challenges and future research prospects in this field.