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RNA origami is a framework for the modular design of nanoscaffolds that can be folded from a single strand of RNA and used to organize molecular components with nanoscale precision. The design of genetically expressible RNA origami, which must fold cotranscriptionally, requires modelling and design tools that simultaneously consider thermodynamics, the folding pathway, sequence constraints and pseudoknot optimization. Here, we describe RNA Origami Automated Design software (ROAD), which builds origami models from a library of structural modules, identifies potential folding barriers and designs optimized sequences. Using ROAD, we extend the scale and functional diversity of RNA scaffolds, creating 32 designs of up to 2,360 nucleotides, five that scaffold two proteins, and seven that scaffold two small molecules at precise distances. Micrographic and chromatographic comparisons of optimized and non-optimized structures validate that our principles for strand routing and sequence design substantially improve yield. By providing efficient design of RNA origami, ROAD may simplify the construction of custom RNA scaffolds for nanomedicine and synthetic biology. 

DNA origami is a modular platform for the combination of molecular and colloidal components to create optical, electronic, and biological devices. Integration of such nanoscale devices with microfabricated connectors and circuits is challenging: Large numbers of freely diffusing devices must be fixed at desired locations with desired alignment. We present a DNA origami molecule whose energy landscape on lithographic binding sites has a unique maximum. This property enabled device alignment within 3.2° on silica surfaces. Orientation was absolute (all degrees of freedom were specified) and arbitrary (the orientation of every molecule was independently specified). The use of orientation to optimize device performance was shown by aligning fluorescent emission dipoles within microfabricated optical cavities. Large-scale integration was demonstrated with an array of 3456 DNA origami with 12 distinct orientations that indicated the polarization of excitation light.

 

Over the last decade, DNA origami has matured into one of the most powerful bottom-up nanofabrication techniques. It enables both the fabrication of nanoparticles of arbitrary two-dimensional or three-dimensional shapes, and the spatial organization of any DNA-linked nanomaterial, such as carbon nanotubes, quantum dots, or proteins at ∼5-nm resolution. While widely used within the DNA nanotechnology community, DNA origami has yet to be broadly applied in materials science and device physics, which now rely primarily on top-down nanofabrication. In this article, we first introduce DNA origami as a modular breadboard for nanomaterials and then present a brief survey of recent results demonstrating the unique capabilities created by the combination of DNA origami with existing top-down techniques. Emphasis is given to the open challenges associated with each method, and we suggest potential next steps drawing inspiration from recent work in materials science and device physics. Finally, we discuss some near-term applications made possible by the marriage of DNA origami and top-down nanofabrication. 

DNA nanotechnology is a materials design paradigm in which synthetic nucleic acids are used to program the structure and dynamics of nanometer-scale devices and materials. Driven by the convergence of decreasing DNA synthesis costs, advanced yet easy-to-use computational design and analysis tools, and, most importantly, a myriad of innovative studies demonstrating DNA’s extraordinary power to organize functional materials, DNA nanotechnology is spreading into diverse areas of traditional materials science. To further promote the integration of DNA nanotechnology into materials science, this issue of MRS Bulletin provides an overview of the unique capabilities offered by DNA nanotechnology, a set of practical techniques that make it accessible to a broad audience, and a vision for its future applications, described by international leaders in the field.