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ACS Nano. 2019 Feb 26;13(2):2083-2093. doi: 10.1021/acsnano.8b08671. Epub 2019 Jan 24.

Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges.

Author information

1
Department of Biological Engineering , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
2
Department of Bioengineering, Microbiology and Immunology, and James H. Clark Center , Stanford University , Stanford , California 94305 , United States.
3
SLAC National Accelerator Laboratory , Stanford University , Menlo Park , California 94025 , United States.

Abstract

3D polyhedral wireframe DNA nanoparticles (DNA-NPs) fabricated using scaffolded DNA origami offer complete and independent control over NP size, structure, and asymmetric functionalization on the 10-100 nm scale. However, the complex DNA sequence design needed for the synthesis of these versatile DNA-NPs has limited their widespread use to date. While the automated sequence design algorithms DAEDALUS and vHelix-BSCOR apply to DNA-NPs synthesized using either uniformly dual or hybrid single-dual duplex edges, respectively, these DNA-NPs are relatively compliant mechanically and are therefore of limited utility for some applications. Further, these algorithms are incapable of handling DNA-NP edge designs composed of more than two duplexes, which are needed to enhance DNA-NP mechanical stiffness. As an alternative, here we introduce the scaffolded DNA origami sequence design algorithm TALOS, which is a generalized procedure for the fully automated design of wireframe 3D polyhedra composed of edges of any cross section with an even number of duplexes, and apply it to DNA-NPs composed uniformly of single honeycomb edges. We also introduce a multiway vertex design that enables the fabrication of DNA-NPs with arbitrary edge lengths and vertex angles and apply it to synthesize a highly asymmetric origami object. Sequence designs are demonstrated to fold robustly into target DNA-NP shapes with high folding efficiency and structural fidelity that is verified using single particle cryo-electron microscopy and 3D reconstruction. In order to test its generality, we apply TALOS to design an  in silico library of over 200 DNA-NPs of distinct symmetries and sizes, and for broad impact, we also provide the software as open source for the generation of custom NP designs.

KEYWORDS:

3D cryo-EM reconstruction; DNA nanotechnology; molecular dynamics; scaffolded DNA origami; six-helix bundle; wireframe origami

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