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DNA origami technique enables the building of virus-sized structures

13.12.2017


Using the DNA origami technology, Hendrik Dietz - TUM-IAS Carl von Linde Senior Fellow and Professor of Biomolecular Nanotechnology at TUM - has been building nanometer-scale objects for several years. Now Dietz and his team have not only broken out of the nanometer realm to build larger objects, but have also significantly reduced the production costs, thereby opening a whole new frontier for the technology.

Viruses encapsulate their genetic material in a shell comprising a series of identical protein building blocks. One example is the hepatitis B virus capsule, which comprises 180 identical subunits - a typical case of “prefabricated” construction often used in nature. The team led by Hendrik Dietz has now transferred these viral construction principles to DNA origami technology, enabling them to design and build structures on the scale of viruses and cell organelles. The technology builds on a long single strand that is appended to a double-stranded structure using short staple sequences. “The double-stranded structure is energetically sufficiently stable so that we can force the single strand into almost any shape using appropriately chosen counterparts,” explains Hendrik Dietz.

Whereas previously the size of the objects remained in the nanometer realm, the team now describes how larger structures can be built using prefabricated parts. For this purpose they first created V-shaped nano-objects which have shape-complementary binding sites on their sides, allowing them to autonomously attach to each other while floating in a solution. Depending on the opening angle, they form “gears” with controlled number of spokes. To further exploit the construction principle, the team created new building blocks that had “glue joints” not only on the sides, but also slightly weaker ones on the top and bottom. This allows the “nano-gears” to form long tubes using the additional docking sites in a second step. “At lengths of one micrometer and a diameter of several hundred nanometers, these tubes have reached the size of some bacteria,” explains Hendrik Dietz.

To date, manufacturing processes have limited the scope of application to those requiring only small amounts of material since the short staple strands must be chemically produced base by base. Therefore the team around Hendrik Dietz refined so-called DNA enzymes, a discovery stemming from synthetic biotechnology. These are DNA strands that break apart at specific positions when exposed to a high concentration of zinc ions. They joined the short staple sequences to a long strand using two modified DNA enzymes each. Dietz explains the key feature of the process as follows: “Once precisely assembled with a specific base sequence, these combined strands can be reproduced in a biotechnological process, as with single strands of bacteriophage DNA”. Both the main strand and the secondary strand, comprising DNA enzymes and the staple sequences, were successfully produced using a high cell density process with bacteria. The process is scalable and thus amenable to high volume production of the main strands and staples.

You can find the full press release here.

Publications:

K. F. Wagenbauer, C. Sigl, H. Dietz. “Gigadalton-scale shape-programmable DNA assemblies”, Nature (2017); DOI: 10.1038/nature24651

F. Praetorius, B. Kick, K. L. Behler, M. N. Honemann, D. Weuster-Botz, H. Dietz. “Biotechnological mass production of DNA origami”, Nature (2017); DOI: 10.1038/nature24650