Three-Dimensional Structures Self-Assembled from DNA Bricks

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Science (Impact Factor: 33.61). 11/2012; 338(6111):1177-83. DOI: 10.1126/science.1227268
Source: PubMed


We describe a simple and robust method to construct complex three-dimensional (3D) structures by using short synthetic DNA strands that we call "DNA bricks." In one-step annealing reactions, bricks with hundreds of distinct sequences self-assemble into prescribed 3D shapes. Each 32-nucleotide brick is a modular component; it binds to four local neighbors and can be removed or added independently. Each 8-base pair interaction between bricks defines a voxel with dimensions of 2.5 by 2.5 by 2.7 nanometers, and a master brick collection defines a "molecular canvas" with dimensions of 10 by 10 by 10 voxels. By selecting subsets of bricks from this canvas, we constructed a panel of 102 distinct shapes exhibiting sophisticated surface features, as well as intricate interior cavities and tunnels.

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Available from: Yonggang Ke, Apr 11, 2014
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    • "The use of DNA structures in biological and biomedical studies is particularly promising due to a number of advantages: DNA structures can be modified with a plethora of (bio)chemical moieties with nanoscale precision [7], there is full control over stoichiometry [8] [9], they are non-cytotoxic [10] [11], they can survive in cell media, blood serum and cultured cells for extended periods of time [12e14] and they can be used as carriers for immune-stimulatory motifs including unmethylated CpG sequences [10] [15]. Particularly the recently introduced DNA tile-assembly method [16] [17] could foster biomedical applications, as the tile-assembly method is extremely versatile, easy to apply, results in high yields of folded structures, and different than in DNA origami applications, no virus-derived scaffold is needed for assembly of DNA nanotubes. Unmethylated CpG sequences have immunogenic properties and are used as adjuvant in vaccination [18] or to overcome tumorassociated immunosuppression [19]. "
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    ABSTRACT: DNA-based nanoconstructs possess great potential for biomedical applications. However, the in vivo behavior of such constructs at the microscopic tissue/cell level as well as their inflammatory potential is largely unknown. Unmethylated CpG sequences of DNA are recognized by Toll-like receptor 9 (TLR9), and thus initiate an innate immune response. In this study, we investigated the use of DNA-based nanotubes as carrier systems for CpG delivery and their effect on immune cells in vivo and in real time. DNA nanotubes were microinjected into skeletal muscle of anesthetized mice. Using in vivo microscopy, we observed that the DNA tubes were internalized within minutes by tissue-resident macrophages and localized in their endosomes. Only microinjection of CpG-decorated DNA nanotubes but not of plain DNA nanotubes or CpG oligonucleotides induced a significant recruitment of leukocytes into the muscle tissue as well as activation of the NF-ĸB pathway in surrounding cells. These results suggest that DNA nanotubes are promising delivery vehicles to target tissue macrophages, whereupon the immunogenic potential depends on the decoration with CpG oligonucleotides. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 06/2015; 53. DOI:10.1016/j.biomaterials.2015.02.099 · 8.56 Impact Factor
    • "The DNA double helix is stabilized by hydrogen bonds formed by complementary nucleotide bases and by the stacking of adjacent bases [2]. The remarkable specificity and robustness of these assemblies has inspired the engineering of several sophisticated structures, through single-stranded DNA self-assembly [3] [4]. Cell membranes are mainly composed of phospholipids, which self-assemble into lipid bilayers. "
    Current Organic Chemistry 06/2015; 19(999):1-1. DOI:10.2174/1385272819666150608220036 · 2.16 Impact Factor
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    • "This technique has paved the way for an efficient, simple and systematic approach to self assembly. Following the method of DNA tiles, Ke et al. extended the idea to DNA bricks [1], which allows the construction of 3D shapes. "
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    ABSTRACT: DNA self-assembly is a robust and programmable approach for building structures at nanoscale. Researchers around the world have proposed and implemented different techniques to build two dimensional and three dimensional nano structures. One such technique involves the implementation of DNA Bricks proposed by Ke et al., 2012 to create complex three-dimensional (3D) structures. Modeling these DNA nano structures can prove to be a cumbersome and tedious task. Exploiting the programmability of base-pairing to produce self-assembling custom shapes, we present a software suite 3DNA, which can be used for modeling, editing and visualizing such complex structures. 3DNA is an open source software which works on the simple and modular self assembly of DNA Bricks, offering a more intuitive better approach for constructing 3D shapes. Apart from modeling and envisaging shapes through a simple graphical user interface, 3DNA also supports an integrated random sequence generator that generates DNA sequences corresponding to the designed model. The software is available at
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