Challenges and opportunities for structural DNA nanotechnology

Andre V. Pinheiro, Dongran Han, William M. Shih, Hao Yan
2011 Nature Nanotechnology  
NATURE NANOTECHNOLOGY | ADVANCE ONLINE PUBLICATION | 1 T he field of structural DNA nanotechnology can be traced back to the words written by Nadrian Seeman in 1982: "It is possible to generate sequences of oligomeric nucleic acids which will preferentially associate to form migrationally immobile junctions, rather than linear duplexes, as they usually do. " 1 Seeman had wanted to organize proteins in three-dimensional (3D) crystals so that he could study
more » ... r structure with X-ray crystallography. Three decades later the field has outgrown its roots in protein crystallography and delivered numerous advances in the control of matter on the nanoscale (Fig. 1) . The history and state of the art in structural DNA nanotechnology have been widely reviewed 2-7 . Here, instead, we seek to stimulate discussions about the future of the field. Research in structural DNA nanotechnology began with the construction of relatively flexible branched junction structures 8 and topological structures 9-16 , progressing to the fabrication of crossover DNA tiles with greater rigidity. These tiles could be used to assemble higher-order periodic and aperiodic lattices 17-30 , and nanotubes 31-37 . A landmark of periodic DNA structure assembly was achieved by Seeman and co-workers 38 in 2009 with the formation of 3D DNA crystals from tensegrity triangles 39 that diffract X-rays to 4 Å resolution. One of the most important development in structural DNA nanotechnology since the introduction of the crossover tile has been the use of a 'scaffold' DNA strand for the assembly of aperiodic structures. It had been previously demonstrated that a long single-stranded DNA chain could be used to organize doublecrossover tiles into barcode-patterned lattices 40 , and that a 1.7-kb single-stranded DNA chain could serve as a scaffold for the assembly of a 3D wire-frame octahedron 41 . The breakthrough came with the concept of 'DNA origami' , where a long scaffold strand (singlestranded DNA from the M13 phage genome, ~7,429 nucleotides long) was folded with the help of hundreds of short 'staple' strands into defined two-dimensional (2D) shapes 42 . The scaffold is thought to corral the component strands in a way that leads to high effective concentrations and proper stoichiometry, so that even unpurified oligonucleotides can be used to produce well-formed 2D structures in near-quantitative yields. DNA origami structures can also be used as molecular pegboards with a resolution of 4-6 nm, and they DNA molecules have been used to build a variety of nanoscale structures and devices over the past 30 years, and potential applications have begun to emerge. But the development of more advanced structures and applications will require a number of issues to be addressed, the most significant of which are the high cost of DNA and the high error rate of self-assembly. Here we examine the technical challenges in the field of structural DNA nanotechnology and outline some of the promising applications that could be developed if these hurdles can be overcome. In particular, we highlight the potential use of DNA nanostructures in molecular and cellular biophysics, as biomimetic systems, in energy transfer and photonics, and in diagnostics and therapeutics for human health.
doi:10.1038/nnano.2011.187 pmid:22056726 pmcid:PMC3334823 fatcat:meoagmjsw5hflco6hhtq2iyqxy