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

Journal Article · · ACS Nano

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. Furthermore, 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.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-76SF00515; CCF-1564025; SC0016353; N000141210621; N000141612953; N000141512830; N000141310664; CMMI-1334109; P41GM103832
OSTI ID:
1507153
Journal Information:
ACS Nano, Vol. 13, Issue 2; ISSN 1936-0851
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 59 works
Citation information provided by
Web of Science

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Cited By (5)

The Topology of Scaffold Routings on Non-Spherical Mesh Wireframes text January 2020
ENSnano: A 3D Modeling Software for DNA Nanostructures text January 2021
Custom-Size, Functional, and Durable DNA Origami with Design-Specific Scaffolds journal April 2019
Automated sequence design of 2D wireframe DNA origami with honeycomb edges journal November 2019
DNA origami protection and molecular interfacing through engineered sequence-defined peptoids journal March 2020

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