DNA origami is the nanoscale folding of
DNA to create non-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.
a well-understood material that is suitable for creating scaffolds
that hold other molecules in place or to create structures all on its
DNA origami was the cover story of Nature on March 16, 2006. Since
DNA origami has progressed past an art form and has found a
number of applications from drug delivery systems to uses as circuitry
in plasmonic devices; however, most applications remain in a concept
or testing phase.
3 Similar approaches
4 See also
The idea of using
DNA as a construction material was first introduced
in the early 1980s by Nadrian Seeman. The current method of DNA
origami was developed by
Paul Rothemund at the California Institute of
Technology, the process involves the folding of a long single strand
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
To produce a desired shape, images are drawn with a raster fill of a
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
Bottom-up self-assembly methods are considered promising alternatives
that offer cheap, parallel synthesis of nanostructures under
relatively mild conditions.
Since the creation of this method, software was developed to assist
the process using CAD software. This allows researchers to use a
computer to determine the way to create the correct staples needed to
form a certain shape. One such software called caDNAno is an open
source software for creating such structures from DNA. The use of
software has not only increased the ease of the process but has also
drastically reduced the errors made by manual calculations.
Many potential applications have been suggested in 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
DNA tube with a hinge on one side which can be clasped shut. The
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
Arizona State University
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
DNA origami inhibits lysosomal acidification,
resulting in cellular redistribution of the drug to action sites, thus
increasing the cytotoxicity against the tumor cells.
In a study conducted by a group of scientists from iNANO center and
DNA Center at Aarhus university, researchers were able to construct a
small multi-switchable 3D
DNA Box Origami. The proposed nanoparticle
was characterized by AFM, TEM and FRET. The constructed box was shown
to have a unique reclosing mechanism, which enabled it to repeatedly
open and close in response to a unique set of
DNA or RNA keys. The
authors proposed that this "
DNA device can potentially be used for a
broad range of applications such as controlling the function of single
molecules, controlled drug delivery, and molecular computing.".
Nanorobots made of
DNA origami demonstrated computing capacities and
completed pre-programmed task inside the living organism was reported
by a team of bioengineers at Wyss Institute at
Harvard University and
Institute of Nanotechnology and Advanced Materials at Bar-Ilan
University. As a proof of concept, the team injected various kinds of
nanobots (the curled
DNA encasing molecules with fluorescent markers)
into live cockroaches. By tracking the markers inside the cockroaches,
the team found the accuracy of delivery of the molecules (released by
the uncurled DNA) in target cells, the interactions among the nanobots
and the control are equivalent to a computer system. The complexity of
the logic operations, the decisions and actions, increases with the
increased number of nanobots. The team estimated that the computing
power in the cockroach can be scaled up to that of an 8-bit
DNA is folded into an octahedron and coated with a single bilayer of
phospholipid, mimicking the envelope of a virus particle. The DNA
nanoparticles, each at about the size of a virion, are able to remain
in circulation for hours after injected into mice. It also elicits
much lower immune response than the uncoated particles. It presents a
potential use in drug delivery, reported by researchers in Wyss
Institute at Harvard University.
The idea of using protein design to accomplish the same goals as DNA
origami has surfaced as well. Researchers at the National Institute of
Chemistry in Slovenia are working on using rational design of protein
folding to create structures much like those seen with
The main focus of current research in protein folding design is in the
drug delivery field, using antibodies attached to proteins as a way to
create a targeted vehicle.
^ Bai, Xiao-chen; Martin, Thomas G.; Scheres, Sjors H. W.; Dietz,
Hendrik (2012-12-04). "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. ISSN 0027-8424.
PMC 3523823 . PMID 23169645.
^ Zadegan, R.M.; Norton, M.L (2012). "Structural
From Design to Applications". Int. J. Mol. Sci. 13: 7149–7162.
doi:10.3390/ijms13067149. PMC 3397516 .
^ Nature, Volume 440 (7082) March 16, 2006
^ http://www.nature.com/news/2010/100310/full/464158a.html 'Nature,
Volume 464 March 10, 2010"
^ a b Seeman, Nadrian C. (1982-11-21). "Nucleic acid junctions and
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^ a b Rothemund, Paul W. K. (2006). "Folding
DNA to create nanoscale
shapes and patterns". Nature. 440 (7082): 297–302.
doi:10.1038/nature04586. ISSN 0028-0836.
^ a b Lin, Chenxiang; Liu, Yan; Rinker, Sherri; Yan, Hao (2006). "DNA
Tile Based Self-Assembly: Building Complex Nanoarchitectures".
ChemPhysChem. 7 (8): 1641–7. doi:10.1002/cphc.200600260.
^ Douglas, Shawn M.; Marblestone, Adam H.; Teerapittayanon, Surat;
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DNA 'organises itself' on silicon,BBC News, August 17, 2009
^ Garde, Damian (May 15, 2012). "
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^ Spickernell, Sarah (8 April 2014). "
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living cockroaches". New Scientist. Retrieved 9 June 2014.
^ Amir, Y; Ben-Ishay, E; Levner, D; Ittah, S; Abu-Horowitz, A;
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^ Gibney, Michael (23 April 2014). "
DNA nanocages that act like
viruses bypass the immune system to deliver drugs".
fiercedrugdelivery.com. Retrieved 19 June 2014.
^ Perrault, S; Shih, W (2014). "Virus-Inspired Membrane Encapsulation
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^ Peplow, Mark (28 April 2013). "Protein gets in on DNA's origami
act". Nature. doi:10.1038/nature.2013.12882.
^ Zadegan, Reza M.; Norton, Michael L. (June 2012). "Structural DNA
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