Abstract

Scaffolded DNA origami enables the bottom-up fabrication of diverse DNA nanostructures by designing hundreds of staple strands, comprised of complementary sequences to the specific binding locations of a scaffold strand. Despite its exceptionally high design flexibility, poor reusability of staples has been one of the major hurdles to fabricate assorted DNA constructs in an effective way. Here we provide a rational module-based design approach to create distinct bent shapes with controllable geometries and flexibilities from a single, reference set of staples. By revising the staple connectivity within the desired module, we can control the location, stiffness, and included angle of hinges precisely, enabling the construction of dozens of single- or multiple-hinge structures with the replacement of staple strands up to 12.8% only. Our design approach, combined with computational shape prediction and analysis, can provide a versatile and cost-effective procedure in the design of DNA origami shapes with stiffness-tunable units.

Highlights

  • To make them, the scaffold pathway, determined by the crosssection shape of DNA bundles and the layout of scaffold crossovers, is a primary design parameter

  • A disadvantage of this approach is that a designer has to replace a large number of staple strands when the design is in need of revision even slightly, because the modification of the pre-determined scaffold pathway induces the sequence alteration of related staples even though they remained at the same position in the structure

  • Our modular design method starts from partitioning the structure by drawing a periodic scaffold path filling the cross-section

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Summary

Introduction

The scaffold pathway, determined by the crosssection shape of DNA bundles and the layout of scaffold crossovers, is a primary design parameter. When the structure had an adjuster strand solely without any hinge module in the body, most structures formed aggregates rather than remained as a monomer The reference structure, consisting of 180 unique staple strands, was folded into a straight bundle as it did not have any hinge and a 504 nucleotide (nt)-long dsDNA adjuster (Supplementary Fig. 6).

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