期刊
ACS NANO
卷 13, 期 2, 页码 2083-2093出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b08671
关键词
DNA nanotechnology; scaffolded DNA origami; wireframe origami; six-helix bundle; 3D cryo-EM reconstruction; molecular dynamics
类别
资金
- National Science Foundation [CCF-1564025, CMMI-1334109]
- Office of Naval Research [N000141310664, N000141512830, N000141612953, N000141210621]
- Department of Energy Office of Science, Office of Basic Energy Sciences [DE-SC0016353]
- National Institutes of Health [P41GM103832]
- U.S. Department of Energy (DOE) [DE-SC0016353] Funding Source: U.S. Department of Energy (DOE)
- U.S. Department of Defense (DOD) [N000141612953, N000141512830] Funding Source: U.S. Department of Defense (DOD)
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 there fore 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.
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