Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges
Name
Automated_Sequence_Design_of_3D_Polyhedral_Wirefra-1.pdf
Description
Accepted version
Size
1.23 MB
Format
Adobe PDF
Checksum (MD5)
c88bf4c89bb81ba3531c906690ae2256
Author(s)
Jun, Hyungmin
Shepherd, Tyson R
Zhang, Kaiming
Bricker, William P
Bathe, Mark
Date Issued
February 2019
Journal
ACS nano
Publisher
American Chemical Society (ACS)
Citation
Jun, Hyungmin et al. “Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges.” ACS nano 13 (2019): 2083-2093 © 2019 The Author(s)
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/ACSNANO.8B08671
