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Science. 2016 Jun 24;352(6293):1534. doi: 10.1126/science.aaf4388. Epub 2016 May 26.

Designer nanoscale DNA assemblies programmed from the top down.

Author information

1
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
4
School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA. Biodesign Center for Molecular Design and Biomimetics (at the Biodesign Institute) at Arizona State University, Tempe, AZ 85287, USA.
5
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. mark.bathe@mit.edu.

Abstract

Scaffolded DNA origami is a versatile means of synthesizing complex molecular architectures. However, the approach is limited by the need to forward-design specific Watson-Crick base pairing manually for any given target structure. Here, we report a general, top-down strategy to design nearly arbitrary DNA architectures autonomously based only on target shape. Objects are represented as closed surfaces rendered as polyhedral networks of parallel DNA duplexes, which enables complete DNA scaffold routing with a spanning tree algorithm. The asymmetric polymerase chain reaction is applied to produce stable, monodisperse assemblies with custom scaffold length and sequence that are verified structurally in three dimensions to be high fidelity by single-particle cryo-electron microscopy. Their long-term stability in serum and low-salt buffer confirms their utility for biological as well as nonbiological applications.

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PMID:
27229143
PMCID:
PMC5111087
DOI:
10.1126/science.aaf4388
[Indexed for MEDLINE]
Free PMC Article

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