期刊
NATURE
卷 552, 期 7683, 页码 72-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature24648
关键词
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资金
- Office of Naval Research grants [N000141010827, N000141310593, N000141410610, N000141612182, N000141612410]
- Army Research Office grant [W911NF1210238]
- National Science Foundation [CCF-1054898, CCF-1162459, CCF-1317291, CMMI-1333215, CMMI-1334109, CMMI-1344915]
- Air Force Office of Scientific Research grant [AFA9550-15- 1-0514]
- National Institute of Health [1DP2OD007292, 1R01EB018659, 167814]
- Emory Biomedical Engineering Department Startup Fund
- Emory Winship Cancer Institute Billi and Bernie Marcus Research Award
- Winship Cancer Institute from American Cancer Society [IRG-14-188-0]
- National Science Foundation CAREER Award [DMR-1654485]
- French National Research Agency [ANR-16- CE09-0004-01, ANR-15-CE09-0003-02, ANR-10-INBS-05]
- NSF graduate research fellowship
- German National Academic Foundation
- German Academic Exchange Service
- International Max Planck Research School for Molecular and Cellular Life Sciences (IMPRS-LS)
- U.S. Department of Defense (DOD) [N000141612410, W911NF1210238, N000141612182] Funding Source: U.S. Department of Defense (DOD)
- Directorate For Engineering
- Div Of Civil, Mechanical, & Manufact Inn [1344915] Funding Source: National Science Foundation
- Div Of Civil, Mechanical, & Manufact Inn
- Directorate For Engineering [1333215] Funding Source: National Science Foundation
- Agence Nationale de la Recherche (ANR) [ANR-16-CE09-0004] Funding Source: Agence Nationale de la Recherche (ANR)
Nucleic acids (DNA and RNA) are widely used to construct nanometre-scale structures with ever increasing complexity(1-14), with possible application in fields such as structural biology, biophysics, synthetic biology and photonics. The nanostructures are formed through one-pot self-assembly, with early kilodalton-scale examples containing typically tens of unique DNA strands. The introduction of DNA origami(4), which uses many staple strands to fold one long scaffold strand into a desired structure, has provided access to megadalton-scale nanostructures that contain hundreds of unique DNA strands(6,7,10-14). Even larger DNA origami structures are possible(15,16), but manufacturing and manipulating an increasingly long scaffold strand remains a challenge. An alternative and more readily scalable approach involves the assembly of DNA bricks, which each consist of four short binding domains arranged so that the bricks can interlock(8,9). This approach does not require a scaffold; instead, the short DNA brick strands self-assemble according to specific inter-brick interactions. First-generation bricks used to create three-dimensional structures are 32 nucleotides long, consisting of four eight-nucleotide binding domains. Protocols have been designed to direct the assembly of hundreds of distinct bricks into well formed structures, but attempts to create larger structures have encountered practical challenges and had limited success(9). Here we show that DNA bricks with longer, 13-nucleotide binding domains make it possible to self-assemble 0.1-1-gigadalton, three-dimensional nanostructures from tens of thousands of unique components, including a 0.5-gigadalton cuboid containing about 30,000 unique bricks and a 1-gigadalton rotationally symmetric tetramer. We also assembled a cuboid that contains around 10,000 bricks and about 20,000 uniquely addressable, 13-base-pair 'voxels' that serves as a molecular canvas for three-dimensional sculpting. Complex, user-prescribed, three-dimensional cavities can be produced within this molecular canvas, enabling the creation of shapes such as letters, a helicoid and a teddy bear. We anticipate that with further optimization of structure design, strand synthesis and assembly procedure even larger structures could be accessible, which could be useful for applications such as positioning functional components.
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