Mansuri, AbdulkhalikAbdulkhalikMansuriJoshi, HetviHetviJoshiKumar, AshutoshAshutoshKumarBhatia, DhirajDhirajBhatia2026-03-182026-03-182026-06-013050-723510.1016/j.nxbio.2026.100019https://repository.iitgn.ac.in/handle/IITG2025/34873The latest developments in DNA nanotechnology have provided new opportunities in immunotherapy and cell engineering through the advancement of exact, biocompatible, and programmable controlling of cell activity. DNA structures have a non-genetic, modular, and reversible platform for changing immune cells, cell membranes, and signaling pathways, as opposed to traditional genetic tools such as viral vectors or CRISPR-based approaches. Some of the applications are DNA origami, hydrogels, tetrahedral frameworks, and spherical nucleic acids which provide spatially regulated ligand presentation, accurate molecule delivery at nanoscale, and receptor clustering. These structures may modify immune cell function, boost T-cell activation, and mix immunomodulatory agents or antigens for targeted therapy. Moreover, DNA nanopores and logic-gated circuits indicate possible application in biosensing, and intelligent therapeutic responses, as well as, cell communication. But despite these improvements, critical translational challenges, e.g., in vivo stability, immunogenicity, manufacturing on a large scale, reproducibility, regulatory standardization among others, still have to be addressed before it can be widely used in clinics. Thus, DNA nanotechnology has been acknowledged as a revolutionary approach to the development of new immunotherapies and regenerative treatments, which are safer, more adaptable and variable than the existing molecular mechanismsen-USTetrahedral DNA nanostructuresCell engineeringTargeted drug deliveryImmunotherapyTranslational challengesArticle