On this page you will find some notes on key advances in the field of structural DNA nanotechnology that are directly related to the research that is done in this lab. Of course, there is a lot more exciting research on DNA and its potential in engineering or computation going on all over the world that is not mentioned here. Insight on the virtues of DNA for engineering is provided by an instructive article by Ned Seeman that is linked below. Links to other research groups working in the field are provided at the bottom of this page.
Nanotechnology and the Double Helix:
How it all started.
Ned Seeman, now at New York University, pioneered the field of structural DNA nanotechnology when he realized in 1979 that covalent phosphate linkages that connect two DNA duplex strands upon homologous recombination during cell division (so-called Holliday junctions) and that usually freely slide along the two connected DNA double helices can be immobilized and thus be used to create a spatially fixed connection between the two DNA duplex molecules - such feat is an elementary requirement for all kind of construction! He wrote an overview article on this and other discoveries that he made and how they started an entire new field of applied science that deals with building things using DNA as construction material. The article also illustrates in detail why DNA is a promising engineering material.
Article and artwork © 2004 Scientific American Inc. There are also a number of comprehensive reviews authored by N Seeman. One of them can be found here: NC Seeman: 'DNA in a material world' NATURE 2003, vol 421 p427
In 2006, Paul Rothemund invented a novel method termed 'scaffolded DNA origami' that builds in part on William Shih's earlier work on 'single-stranded DNA origami'. Paul's new method did not only take the objects that could by then be engineered with DNA to an unprecedented level of complexity and size, but also the many different two-dimensional shapes that he was able to build (such as 100-nanometer-wide smiley-faces) inspired people from many different fields - even artists! Scaffolded DNA origami has conceptual similarities to protein folding: It relies on folding a long 'backbone' DNA molecule into a desired shape by introducing interactions between different segments of the backbone molecule. These interactions are expressed by a set of short single stranded 'staple' DNA molecules that are added to the backbone molecule. Paul's method removed with a bang technical difficulties such as tedious purification requirements and stoichiometry issues that long troubled researchers in the field of DNA-based nanotechnology. Above is a video showing Paul explaining his method.
Warps and Wefts: DNA Origami now in 3D!
Immediately after Paul Rothemund published his new method in 2006, a number of research groups directed their efforts towards extending Paul Rothemund's scaffolded DNA origami method to creating three-dimensional nanoscale shapes. Among them was a team from the Danish Center for DNA Nanotechnology at Aarhus University, as well as Hao Yan's Group from Arizona State University, and also a team headed by William Shih at Harvard Medical School, which HD joined in early 2007.
Hao Yan and his students published soon their first three-dimensional DNA origami shape, a tetrahedron (Ke et al, JACS 2009), while the Danish team came up with a DNA box with a switchable lid (Anderson et al, NATURE 2009). Meanwhile, in the Shih Lab, we were still soldiering on a general route towards engineering of custom three-dimensional shapes constructed from DNA, which eventually got published as well. (see the original articles: 1, 2 and published research).
The volume of space accessible by our initial methods was confined to a honeycomb-raster pattern and it was discrete, meaning that addressable coordinates are individual bases on DNA double-helices that are arranged on the raster pattern. Soon after we also discovered methods how to build curved and twisted shapes, thereby breaking down the limits of the rasterization and discretization. Thus, in principle, one would be able now to direct individual atoms in nucleic acid molecules to desired positions in space with near-atomic resolution - if it were not for a number of lingering issues such as prevailing folding defects, somewhat unclear DNA materials properties, and unsatisfactorily rigidity that will have to be addressed in the future (see also our current directions).
Read the feature on DNA Origami in the Wall Street Journal.
'Self-assembly of DNA into nanoscale three-dimensional shapes' NATURE 2009
Computer-Aided Design for DNA origami
Shawn Douglas, back then one of the members of the original Shih-lab origami team, and coworkers made a great contribution when they cast all the architectural rules that we found necessary so far for designing DNA origami objects into an open-source platform-independent software called caDNAno. It is really easy to use and makes designing DNA objects significantly less error-prone, faster, and much more fun! Download it from http://cadnano.org. Shawn also provides a number of tutorials that will help you getting started.
There are other software packages around, notably SARSE, developed by Ebbe S. Andersen in Aarhus, and NanoEngineer from NanoRex, Inc. that offer a good deal of related functionalities.
However, a challenge for the future remains to develop software for computer-aided engineering, i.e. tools that allow you finding optimal solutions to a given 'nano'-engineering task.