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. Shih1,2,3Department of Cancer Biology, Dana-Farber Cancer InstituteDepartment 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.