DNA nanotechnology in therapeutic modulation and bio-inspired systems for precision medicine

Abstract

Nucleic acid nanotechnology, particularly DNA-based nanostructures, is fundamentally reshaping the paradigms of drug delivery and therapeutics, by leveraging their high programmability, precise self-assembly capabilities, and superior biocompatibility. Beyond constructing static frameworks with prescribed dimensions and geometries, such as tetrahedral DNA nanostructures (TDNs), DNA origami, and spherical nucleic acids (SNAs), these molecular entities can be engineered via dynamic sequence design to facilitate intelligent responsiveness to environmental stimuli [1, 2]. Such molecular-level engineering versatility positions DNA nanostructures as a pivotal conduit bridging fundamental biological insights and clinical precision medicine. As the field matures, DNA nanotechnology is demonstrating transformative potential in cancer immunotherapy, the modulation of intercellular communication, and the construction of engineered biomodels. Leveraging its digital programmability, it has evolved from simple carrier development into a sophisticated molecular engineering platform, enabling the quantitative modulation of complex biological processes with single-nucleotide precision. By utilizing DNA nanostructures as “molecular calipers”, researchers employ Watson-Crick base-pairing principles to precisely define the inter-binding site distances (e.g., 18–20 nm) [3, 4]. This allows for perfect topological matching