DNA nanotechnology

Chemistry
A. Paul Alivisatos
Samsung Distinguished Professor of Nanoscience and Nanotechnology, and Professor of Chemistry and Materials Science & Engineering, and Director of Lawrence Berkeley National Laboratory, University of California, Berkeley, Berkeley, California USA
Chad A. Mirkin
George B. Rathmann Professor of Chemistry, Northwestern University, Evanston, Illinois, USA
Nadrian C. Seeman
Margaret and Herman Sokol Professor of Chemistry, New York University, New York, NY USA

Alivisatos, Mirkin, and Seeman are suggested as possible Nobel Prize winners “for contributions to DNA nanotechnology”

Colloids have been used for centuries as pigments. The ruby color of stained glass, for example, comes from colloidal particles of gold. We now know that the behavior of such materials is due to their being nanosized clusters of metal atoms. Formerly they had relatively few scientific uses. Although used as high-contrast stains for electron microscopy, they attracted little interest from chemists, mainly because they were not molecules as such. Today, they are a hot topic, and their combination with DNA has been particularly fruitful. DNA is nature’s most important and complex molecule, and coupling it to metal nanoparticles has yielded remarkable results. This area is now termed DNA nanotechnology, and three chemists have been responsible for its innovation: Alivisatos, Mirkin, and Seeman.

Alivisatos is a world expert on the chemistry of nanoscale crystals; one of his papers (Science, 271: 933-937, 1996) has been cited 6,400 times. He is also an expert on how these can be applied, for example as biological markers (e.g., Science, 281: 2013-6, 1998; a paper cited 4,400 times). His use of DNA in this area has shown how versatile DNA really can be. He has used it to direct crystal growth and create new materials, as in Nature, 382: 609-11, 1996, and even to measure nanoscale distances (see Nature Nanotechnology, 1: 47-52, 2006).

Chad Mirkin has published 11 research papers that have each been cited more than 1,000 times. His most-cited report, with nearly 3, 000 citations, concerns a method of using DNA to assemble nanoparticles into larger and more useful materials (Nature, 382: 607-9, 1996). The method involves DNA oligonucleotides to which are attached sulfur (SH) groups that attract and bond gold atoms. In a recent paper he has shown that it is possible to dissolve away the gold to produce spherical nucleic acids with interesting properties (see J. Am. Chem. Soc., 134: 1376-91, 2012). Another key paper, in Science (289: 1757-60, 2000; cited 1,500 times), concerns the analysis of combinatorial DNA arrays using nanoparticle probes.

Nadrian Seeman brought DNA and nanotechnology together in a most productive manner. One of his reports, from Nature (394: 539-44, 1998; now cited nearly 1,200 times), describes the design and self-assembly of two-dimensional DNA crystals, a process enabling the creation of specific repeating units on the nanoscale which are analyzable by atomic force microscopy. An early paper, entitled “Synthesis from DNA of a molecule with the connectivity of a cube” also appeared in Nature (350: 631-3, 1991) and hinted at what was to come, although he says that he was alerted to the possibility of constructing three-dimensional DNA lattices ten years earlier and speculated on this in a paper submitted to the Journal of Theoretical Biology (99: 237-47) in 1982.


Commentary on the Chemistry Laureates by John Emsley, Chemistry correspondent, ScienceWatch. Dr. Emsley is based at the Department of Chemistry, University of Cambridge, UK.

Interview with A. Paul Alivisatos, Samsung Distinguished Professor of Nanoscience and Nanotechnology, Professor of Chemistry and Materials Science & Engineering, and Director of Lawrence Berkeley National Laboratory, University of California Berkeley.

For contributions to DNA nanotechnology

A. Paul AlivisatosQPlease provide a brief overview of your field of research.

AMy coworkers and I are engaged in the study of colloidal inorganic nanocrystals. These small crystals have unusual properties that depend strongly on their size and shape. We have developed new methods for preparing these nanocrystals, and we have investigated their structural, optical, and electrical properties. In addition, we have developed their applications in biological imaging and renewable energy.

QWhat led you to focus in this area?

AThis area of research is situated between chemistry and physics. It also lies between basic and applied research, requiring a careful interplay of the two. It is an area with enormous opportunity, and it appeals to me because it is such a rich and diverse topic.

QWhat did you want to accomplish when you began your research?

AI wanted to be able to understand how the properties of a solid evolve from when it is comprised of just a few atoms, to the point where it is so large that it is not practical to count the atoms anymore.

QWhat notable problems, challenges, or obstacles did you face? Conversely, have there been particular sources of enjoyment, satisfaction, or pride?

AIn the early years of this work, it was very difficult to make high-quality nanocrystals of uniform size. It is amazing to me to see how easy this is to do now and to see just how widespread the study of nanocrystals has become. I believe nanocrystals are well on the way to becoming a fundamental building block of materials chemistry and one day will be as widely used as polymers are today.

QHow would you assess the importance and influence of your work?

AI think it is better for me to let others do that.

QHas this research found wider application outside of academia, such as in political or policy areas? If so, how is such development likely to continue?

ANanocrystal quantum dots are widely used as luminescent labels in biomedicine and are now being used in displays and televisions.

Interview with Nadrian Seeman, Margaret and Herman Sokol Professor of Chemistry, New York University.

For contributions to DNA nanotechnology

Nadrian C. SeemanQPlease provide a brief overview of your field of research.

A My field of research is DNA nanotechnology. I founded this field in a bar in Albany, New York, in 1980, where I had gone to think about 6-arm DNA branched junctions. While thinking about them, I suddenly thought about Escher's woodcut, 'Depth', which consists of a crystalline arrangement of fish with top, right, bottom and left fins, in addition to their heads and tails. I realized that the fish were topologically isomorphous with 6-arm junctions, and that if 6-arm (or other) junctions could be held together by DNA sticky ends, they could be self-assembled into crystalline arrangements hosting other macromolecules, thereby defeating the crystallization problem of macromolecular crystallography. Over the years, we have built objects, crystalline lattices (so far without guests) and nanomechanical devices. DNA is also the best possible synthon for topological species, such as knots, catenanes and other links, all of which we have explored. We have built a nanoscale assembly line from DNA, and we have organized other species like nanoparticles and amyloid fibrils. Our focus has been particularly on the highest quality structural species, but others have developed larger objects from 'DNA origami' [Paul Rothemund], and large numbers of small strands [Peng Yin]; the criteria for these constructs is lower than for the crystalline materials that we self-assemble. DNA nanotechnology also has appiications in DNA-based computation, starting with algorithmic assembly [first suggested by Erik Winfree].

QWhat led you to focus in this area?

AThe field combined everything that I liked: Crystallography, symmetry, topology, geometry, nucleic acids, information, 3D thinking and analysis, and it gave me an outlet for my creative urges.

Q What did you want to accomplish when you began your research?

A I wanted to solve the crystallization problem of macromolecular crystallography; I was terrible at crystallizing things, and wanted a way to obviate the trial-and-error aspects of the activity.

QWhat notable problems, challenges, or obstacles did you face? Conversely, have there been particular sources of enjoyment, satisfaction, or pride?

AOur biggest problem has been producing crystals of adequate resolution. We keep working to improve the 3-4 Å resolution of the crystals that we are able to self-assemble. Of course the first object (a catenane with the connectivity of a cube), the first 2D crystalline array, the first DNA-based nanomechanical devices, the construction of Borromean rings, and the first 3D crystalline arrays were particularly satisfying.

QHow would you assess the importance and influence of your work?

Q We have been the first group to use molecular information to self-assemble materials. We were alone in the field for about 20 years, but now there are probably more than 100 laboratories doing something based on using DNA information to control and organize the structure of matter, at least on the nanometer scale.

QHas this research found wider application in industrial or commercial areas? If so, what are some possible future developments?

A People [including our laboratory] are trying to apply DNA nanotechnology to building crystals so that we can look at drug leads interacting with receptors, to organize nanoelectronics, to build self-replicating materials, to calibrate modern X-ray optics, to examine the recognition of DNA-DNA recognition in the cell, and to build therapeutic systems. So far I am unaware of any companies marketing anything based on our work.

Q Is there anything else you’d like to share about your work or this field of study?

A It's been a lot of fun building a career based on exploiting the things in science that I find the most beautiful and exciting. There have been a lot of difficulties and frustrations, but I can't think of a better way to have spent my life.