DNA origami

DNA origami object from viral DNA visualized by electron microscopy.Bai, X. -C.; Martin, T. G.; Scheres, S. H. W.; Dietz, H. (2012). "Cryo-EM structure of a 3D DNA-origami object". Proceedings of the National Academy of Sciences 109 (49): 20012–20017. doi:10.1073/pnas.1215713109. PMID 23169645. . The map is at the top and atomic model of the DNA colored below. Deposited in EMDB EMD-2210

DNA origami is the nanoscale folding of DNA to create arbitrary two and three dimensional shapes at the nanoscale. The specificity of the interactions between complementary base pairs make DNA a useful construction material, through design of its base sequences.

Method

Developed by Paul Rothemund at the California Institute of Technology, the process involves the folding of a long single strand of viral DNA aided by multiple smaller "staple" strands. These shorter strands bind the longer in various places, resulting in various shapes, including a smiley face and a coarse map of China and the Americas, along with many three-dimensional structures such as cubes.

To produce a desired shape, images are drawn with a raster fill of a single long DNA molecule. This design is then fed into a computer program that calculates the placement of individual staple strands. Each staple binds to a specific region of the DNA template, and thus due to Watson-Crick base pairing, the necessary sequences of all staple strands are known and displayed. The DNA is mixed, then heated and cooled. As the DNA cools, the various staples pull the long strand into the desired shape. Designs are directly observable via several methods, including Electron Microscopy, atomic force microscopy, or fluorescence microscopy when DNA is coupled to fluorescent materials.

Bottom-up self assembly methods are considered promising alternatives that offer cheap, parallel synthesis of nanostructures under relatively mild conditions.

Applications and studies

Many potential applications have been suggested in the literature, including enzyme immobilization, drug carry capsules, and nanotechnological self-assembly of materials. Though DNA is not the natural choice for building active structures for nanorobotic applications, due to its lack of structural and catalytic versatility, several papers have examined the possibility of molecular walkers on origami and switches for algorithmic computing. The followings list some of the reported applications conducted in the laboratories with clinical potential.

• Researchers at the Harvard University Wyss Institute reported the self-assembling and self-destructing drug delivery vessels using the DNA origami in the lab tests. The DNA nanorobot they created is an open DNA tube with a hinge on one side which can be clasped shut. The drug filled DNA tube is held shut by DNA aptamer, configured to identify and seek certain diseased related protein. Once the origami nanobots get to the infected cells, the aptamers break apart and release the drug. The first disease model the researchers used was leukemia and lymphoma.

• Researchers in the National Center for Nanoscience and Technology in Beijing and Arizona State University reported a DNA origami delivery vehicle for Doxorubicin, a well-known anti-cancer drug. The drug was non-covalently attached to DNA origami nanostructures through intercalation and a high drug load was achieved. The DNA-Doxorubicin complex was taken up by human breast adenocarcinoma cancer cells (MCF-7) via cellular internalization with much higher efficiency than doxorubicin in free form. The enhancement of cell killing activity was observed not only in regular MCF-7, more importantly, also in doxorubicin-resistant cells. The scientists theorized that the doxorubicin-loaded DNA origami inhibits lysosomal acidification, resulting in cellular redistribution of the drug to action sites, thus increasing the cytotoxicity against the tumor cells.

Impact

DNA origami was the cover story of Nature on March 16, 2006.

See also

• DNA nanotechnology
• Molecular self-assembly
• Folding@home