Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges
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 DN...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125281 |
| _version_ | 1826213484381077504 |
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| author | Jun, Hyungmin Shepherd, Tyson R Zhang, Kaiming Bricker, William P Bathe, Mark |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Jun, Hyungmin Shepherd, Tyson R Zhang, Kaiming Bricker, William P Bathe, Mark |
| author_sort | Jun, Hyungmin |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:50:16Z |
| format | Article |
| id | mit-1721.1/125281 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:50:16Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1252812022-10-02T04:26:49Z Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges Jun, Hyungmin Shepherd, Tyson R Zhang, Kaiming Bricker, William P Bathe, Mark Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering 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. National Science Foundation (U.S.) (Grant CCF-1564024) National Science Foundation (U.S.) (Grant CMMI-1334109) United States. Office of Naval Research (Grant N000141210621) United States. Office of Naval Research (Grant N000141612953) United States. Department of Energy. Office of Basic Energy Sciences (Grant DE-SC0016353) National Institutes of Health (U.S.) (Grant P41GM103832) United States. Office of Naval Research (Grant N000141612953) United States. Office of Naval Research (Grant N000141310664) United States. Office of Naval Research (Grant N000141512830) 2020-05-18T14:08:22Z 2020-05-18T14:08:22Z 2019-02 2020-03-04T16:39:45Z Article http://purl.org/eprint/type/JournalArticle 1936-0851 https://hdl.handle.net/1721.1/125281 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) en 10.1021/ACSNANO.8B08671 ACS nano 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. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Jun, Hyungmin Shepherd, Tyson R Zhang, Kaiming Bricker, William P Bathe, Mark Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges |
| title | Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges |
| title_full | Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges |
| title_fullStr | Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges |
| title_full_unstemmed | Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges |
| title_short | Automated Sequence Design of 3D Polyhedral Wireframe DNA Origami with Honeycomb Edges |
| title_sort | automated sequence design of 3d polyhedral wireframe dna origami with honeycomb edges |
| url | https://hdl.handle.net/1721.1/125281 |
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