合成特定形状纳米尺度DNA结构的新方法

纳米技术的一个重要目标是复杂、三维纳米结构的可编程自我组装。以DNA为构造单元，合成方法已经发展到了可生成二维设计机构和某些三维结构的阶段。Douglas等人介绍了对脚手架式DNA折纸方法的一种优化，新方法能够生成有或多或少的任何所期望形式的三维目标，尺度达到10到100纳米，并且对各种不同的DNA螺旋之位置的控制也达到了令人印象深刻的程度。这种合成方法涉及排列成褶皱链及组装成蜂巢状三维结构的DNA螺旋。各种不同的DNA链通过磷酸基团连接在一起。这种方法能够生成组装速度慢的复杂目标，但它也为组装具有纳米尺度特征的定制器件提供了一个途径，如研究人员已经用这种方法构建出了形状像方螺帽、十字槽和线框二十面体的目标。

Nature 459, 414-418 （21 May 2009） | doi:10.1038/nature08016; Received 16 December 2008; Accepted 24 March 2009

Self-assembly of DNA into nanoscale three-dimensional shapes

Shawn M. Douglas1,2,3, Hendrik Dietz1,2, Tim Liedl1,2, Bjorn Hogberg1,2, Franziska Graf1,2,3 & William M. Shih1,2,3

Department of Cancer Biology, Dana-Farber Cancer Institute
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
Correspondence to: William M. Shih1,2,3 Correspondence and requests for materials should be addressed to W.M.S. （Email: william_shih@dfci.harvard.edu）。

Top of pageMolecular self-assembly offers a 'bottom-up' route to fabrication with subnanometre precision of complex structures from simple components. DNA has proved to be a versatile building block for programmable construction of such objects, including two-dimensional crystals, nanotubes, and three-dimensional wireframe nanopolyhedra. Templated self-assembly of DNA into custom two-dimensional shapes on the megadalton scale has been demonstrated previously with a multiple-kilobase 'scaffold strand' that is folded into a flat array of antiparallel helices by interactions with hundreds of oligonucleotide 'staple strands'. Here we extend this method to building custom three-dimensional shapes formed as pleated layers of helices constrained to a honeycomb lattice. We demonstrate the design and assembly of nanostructures approximating six shapes-monolith, square nut, railed bridge, genie bottle, stacked cross, slotted cross-with precisely controlled dimensions ranging from 10 to 100 nm. We also show hierarchical assembly of structures such as homomultimeric linear tracks and heterotrimeric wireframe icosahedra. Proper assembly requires week-long folding times and calibrated monovalent and divalent cation concentrations. We anticipate that our strategy for self-assembling custom three-dimensional shapes will provide a general route to the manufacture of sophisticated devices bearing features on the nanometre scale.