Chemically Conjugated Branched Staples for Super-DNA Origami

DNA origami, comprising a long folded DNA scaffold and hundreds of linear DNA staple strands, has been developed to construct various sophisticated structures, smart devices, and drug delivery systems. However, the size and diversity of DNA origami are usually constrained by the length of DNA scaffolds themselves. Herein, we report a new paradigm of scaling up DNA origami assembly by introducing a novel branched staple concept. Owing to their covalent characteristics, the chemically conjugated branched DNA staples we describe here can be directly added to a typical DNA origami assembly system to obtain super-DNA origami with a predefined number of origami tiles in one pot. Compared with the traditional two-step coassembly system (yields <10%), a much greater yield (>80%) was achieved using this one-pot strategy. The diverse superhybrid DNA origami with the combination of different origami tiles can be also efficiently obtained by the hybrid branched staples. Furthermore, the branched staples can be successfully employed as the effective molecular glues to stabilize micrometer-scale, super-DNA origami arrays (e.g., 10 x 10 array of square origami) in high yields, paving the way to bridge the nanoscale precision of DNA origami with the micrometer-scale device engineering. This rationally developed assembly strategy for super-DNA origami based on chemically conjugated branched staples presents a new avenue for the development of multifunctional DNA origami-based materials.