Namaste everyone! Remember me from the last post? The guy who got interviewed by Ellen, on The Ellen Show? In his dreams? Yeah, that was me (if not check it out here). So today I will be talking about some sciency stuff because our DNA Robotics consortium is themed on DNA Nanotechnology. So, let’s slide along the strands of Functional DNA Nanotechnology (awkward attempt at generating humour):

A throwback?
A long time ago, in 1980, a crystallographer by the name of Nadrian Seeman, bogged down by the problems of macromolecular crystallisation, looked at DNA as a new tool to make crystals. Seeman was programming and simulating DNA structures, but there were still some problems related to branching and symmetry, and along with his students and postdocs he was trying to find ways to overcome this. One eventual evening Prof. Seeman was having beer at his university pub, when his eyes fell on a woodcut named ‘Depth’. It had nothing to do with DNA but the woodcut had flying fish arranged with periodic stability in all 4 directions. For him, this represented a 6-arm DNA junction, which got him wondering about, and he quotes, “Maybe I could use this concept to make crystals, to get crystals to self-associaterather than simply to try to crystallize them in the usual method of throwing stuff in a pot and invoking one deity after another to get the crystals.” That evening in the pub marked the beginning of a field that in the upcoming years would change our perception of DNA. Thus, Prof. Ned Seeman is credited to be the founder of DNA Nanotechnology.

(See, beer is always a good idea, now you know what to do when your experiments don’t come along)

Fast forward 26 years: On 16 March 2006, Paul Rothemund, a research professor of Bioengineering and Computation from Caltech, published a paper in Nature titled ‘Folding DNA to create nanoscale shapes and patterns’. Rothemund had developed a novel method for folding DNA in different shapes with precision of a few nanometers i.e. a thousand times thinner than our hair! The paper revolutionised the field of DNA Nanotechnology and introduced DNA Origami to the world.

Rothemund origami structures
Figure1. The first DNA Origami structures fabricated by P.Rothemund

(Rothemund, Paul WK. “Folding DNA to create nanoscale shapes and patterns.” Nature 440, 7082 (2006): 297.)

So, What is DNA Nanotechnology?
All of us know DNA as a material that stores and transmits genetic information, it encodes proteins and carries instructions for many other biological processes, but DNA Nanotechnology removes this wonder molecule from its biological context. In a generalised view, DNA Nanotechnology is the controlled manipulation of DNA at a molecular level, which is necessary for addressing the exclusive properties of DNA that set it apart from other biological molecules: the impeccable binding specificity amongst the nitrogen bases (i.e. adenine always bonds with thymine and guanine always bonds with cytosine), its high thermodynamical stability, and its ability to self-assemble.

DNA Origami is possibly the largest subplot in the DNA Nanotechnology scene, and it is quite similar to the Japanese art of paper origami, except DNA is used instead of paper (and some chemicals… and some machines). The idea is to use a long DNA strand called the scaffoldand fold it into different shapes using smaller DNA strands called staples. Using specific software, an origami shape is designed based on a scaffold strand and the software generates the required staples to fold the desired origami. The scaffold and staples are then mixed, with temperature and time being the physical parameters to be controlled, and eventually, the structures are purified and visualised using transmission electron microscopy or atomic force microscopy.

Check this out – DNA Origami Introduction Video

Why DNA Nanotechnology? And what are the applications?
Because of DNA’s very specific binding pattern, DNA strands can be designed for the bottom-up synthesis of materials in the nanometer regime. Bottom-up synthesis implies the creation of materials by starting at the atomic or molecular scale and gradually reaching the desired size, whereas the top-down approach implies breaking down of a bulky material to a smaller desired size. Synthesis at this level usually follows molecular self-assembly and fabrication of structures of a range of versatile shapes is possible because of DNA’s programmability and self-assembly attributes. DNA Nanotechnology has the conceptual basis of Programmable Matter, which simply means the ability to change physical properties upon interaction with an input or through autonomous sensing. Because DNA can be easily functionalized with small proteins and molecules and its synthesis  is both inexpensive and controllable, the field of DNA Nanotechnology is capable of transforming a lot of existing systems including drug delivery, sensing systems, and molecular electronics. The applications range far, and some research groups focus on the construction of drug delivery systems for controlled and targeted delivery, others attempt to use DNA for computation and processing, whereas yet others are exploring the use of DNA nanostructures for studying cell signalling and communication. Work is also progressing along the lines of construction of bio-inspired molecular machines, and molecular electronics, sensing and switching systems fabricated using DNA are also coming up.

The current focus of work amongst prominent research groups in the world
Prof. Ned Seeman settled with his research group at New York University. Still among the most prominent research groups in the work, his group assembles 2D and 3D DNA crystals, cubes, and octahedrons in addition to caging molecules within DNA origami structures.
Caltech houses the groups of Prof. Paul Rothemund, who works on the integration of DNA origami structures into microfabricated devices for nanoelectronics and nanophotonics, and Prof. Eric Winfree,  a computer scientist, whose research work is focussed on DNA-based computation and information processing. Another lab in the US is the lab of Prof. Shawn Douglas at UCSF, who along with
Prof. William Shih from Harvard developed the caDNAno software for rendering and designing DNA origami structures.
The Technical University of Munich harbours 2 research groups working in this discipline, the groups of Prof. Hendrik Dietz and Prof. Freidrich Simmel. In the Dietz Lab, the work is concentrated on constructing different DNA Origami structures and molecular machines, and they are also scaling up DNA Origami production. The Simmel Lab (this is where I work btw) focuses on the interaction of DNA origami structures with interfaces like membranes, particles, and droplets, and we also work on molecular motors and synthetic biology. The group of Prof. Tim Liedl is also based in Munich at the LMU. Their work is focussed on DNA-mediated self-assembly and nanoengineering.

The iNANO center at Aarhus University houses the group of Prof. Kurt Gothelf, which work on the functionalization of DNA origami structures with biomolecules like proteins and developing DNA origami structures for drug delivery. The group of Assoc. Prof. Ebbe Andersen is also based here and they create complex RNA and DNA origami structures, but they also aim at creating new visual tools and software for better communication of data.

The Högberg lab at Karolinska Instituet works on the production of DNA oligonucleotides and drug delivery using DNA nanostructures. The Ricci lab in Rome is working on building sensing and switching systems using DNA origami structures conjugated with various biomolecules. In Oxford, the group of Prof. Andrew Tuberfield focuses on the fabrication of DNA lattices, molecular motors, and 3D DNA nanostructures.
And there are many more labs around the world.

The field has developed extensively since its inception. Continous autonomous research has broadened what this field stands for and there is so much more to where it can go. Promising results obtained in upscaling the synthesis and building novel structures followed by applications in molecular electronics, medical diagnostics, environmental sensing, nanoscaled motors has piqued the interest of many scientists and it does not look to dwindle.

Further reading
If you would like to read more keep watching this space as my peers will keep posting exciting stuff, you can hit me up too, and here are some links for words right from the pros:
–  A conversation with Prof. Ned Seeman

Prof. Paul Rothemund’s awesome TED Talks

–  An insight into molecular machines and motors by Prof. Hendrik Dietz

William Shih’s insightful introductions to DNA Origami

So, that was my time, I hope I did half a decent job introducing you to this field, my friends will come in with their blog posts as well so be sure to stay with us. Until next time.

Written by Yash Bogawat, PhD student at the Technical University in Munich

Image credits for the DNA Cover
Creator: MR.Cole Photographer
Credit: Getty ImagesImage credits



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