Self-Assembly of Geometry-Based DNA Origami-Histone Protein Hybrid Nanostructures for Constructing Rationally-Designed Higher-Order Structures

The emergence of hybrid DNA-protein hybrid nanostructures in recent years has expanded the application of DNA nanotechnology. Previous studies reported the integration of proteins into DNA nanostructures by sequence-dependent interactions or chemical modifications of DNA, which limit the design flexibility of hybrid nanostructures. Here we report the construction of sequence-independent geometry-based DNA-protein hybrid nanostructures using the self-assembly of single-stranded (ss) DNA and histone proteins. We demonstrate that nucleosome-like ssDNA-histone complexes are integrated into various shapes of DNA origami at specific predefined locations. We further show the possibility of using these hybrid nanostructures as the building blocks for designing more complex nanostructures. Our finding would facilitate the development of geometry-based sequence-independent predesigned DNA-protein hybrid nanostructures for more flexible and straightforward construction of higher-order structures.