Abstract

DNA nanostructures with increasing complexity have showcased the power of programmable self-assembly from DNA strands. At the nascent stage of the field, a variety of small branched objects consisting of a few DNA strands were created. Since then, a quantum leap of complexity has been achieved by a scaffolded ‘origami’ approach and a scaffold-free approach using single-stranded tiles/bricks—creating fully addressable two-dimensional and three-dimensional DNA nanostructures designed on densely packed lattices. Recently, wireframe architectures have been applied to the DNA origami method to construct complex structures. Here, revisiting the original wireframe framework entirely made of short synthetic strands, we demonstrate a design paradigm that circumvents the sophisticated routing and size limitations intrinsic to the scaffold strand in DNA origami. Under this highly versatile self-assembly framework, we produce a myriad of wireframe structures, including 2D arrays, tubes, polyhedra, and multi-layer 3D arrays.

Highlights

  • DNA nanostructures with increasing complexity have showcased the power of programmable self-assembly from DNA strands

  • Despite scaffold-free assembly’s capacity to employ up to 33,000 distinct strands[21] as compared to DNA origami’s 1600 distinct strands[22], complex wireframe architectures have not been fully demonstrated with the scaffold-free approach[23,24,25,26,27,28,29,30,31,32,33]

  • A typical process in designing a wireframe structure from short synthetic strands is straightforward[35], and it is pipelined as: (1) rendering a specific 2D or 3D geometry (Fig. 1a) as a node-edge network with DNA junctions of different numbers of arms as nodes and DNA duplexes of variable lengths as edges (Fig. 1b), (2) segmenting edges to complementary domains to ensure that corresponding strands with multiple domains satisfy synthesis and self-assembly requirements (Fig. 1c), and (3) populating strands with sequences to meet certain sequence generation criteria[36] (Fig. 1d)

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Summary

Introduction

DNA nanostructures with increasing complexity have showcased the power of programmable self-assembly from DNA strands. Revisiting the original wireframe framework entirely made of short synthetic strands, we demonstrate a design paradigm that circumvents the sophisticated routing and size limitations intrinsic to the scaffold strand in DNA origami. Under this highly versatile selfassembly framework, we produce a myriad of wireframe structures, including 2D arrays, tubes, polyhedra, and multi-layer 3D arrays. The advantages of using a scaffold-free approach to assemble complex wireframe structures entirely out of short DNA strands are clear: the design process would be streamlined without having to route a long scaffold, and structure size would no longer be constrained by scaffold length. A reincarnation of the original blueprint of DNA nanotechnology, our findings in this study redefine the feasibility of using flexible components to self-assemble DNA nanostructures in an adaptive fashion

Methods
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