RNA–DNA Hybrid Nanoshape Synthesis by Facile Module Exchange

The preparation of nucleic acid nanostructures has relied predominantly on procedures of additive fabrication in which complex architectures are assembled by concerted self-assembly and sequential addition of building blocks. We had previously established RNA–DNA hybrid nanoshapes with modular architectures that enable multistep synthetic approaches inspired by organic molecular synthesis where additive and transformative steps are used to prepare complex molecular architectures. We report the establishment of module replacement and strand exchange as synthetic transformations in nucleic acid hybrid nanoshapes, which are enabled by minimally destabilizing sequence elements such as a single unpaired overhang nucleotide or a mismatch base pair. Module exchange facilitated by thermodynamic lability triggers adds a powerful transformative approach to the repertoire of additive and transformative synthetic methods for the preparation of complex composite materials.