Scientists Create Single, Clonable Strand of DNA That Folds
into an Octahedron
By Jason Socrates Bardi
A group of scientists at The Scripps Research Institute
has designed, constructed, and imaged a single strand of DNA
that spontaneously folds into a highly rigid, nanoscale octahedron
that is several million times smaller than the length of a
standard ruler and about the size of several other common
biological structures, such as a small virus or a cellular
Making the octahedron from a single strand was a breakthrough.
Because of this, the structure can be amplified with the standard
tools of molecular biology and can easily be cloned, replicated,
amplified, evolved, and adapted for various applications.
This process also has the potential to be scaled up so that
large amounts of uniform DNA nanomaterials can be produced.
These octahedra are potential building blocks for future projects,
from new tools for basic biomedical science to the tiny computers
"Now we have biological control, and not just synthetic
chemical control, over the production of rigid, wireframe
DNA objects," says Research Associate William Shih of Scripps
Shih led the research, described in the latest issue of
the journal Nature, with Professor Gerald Joyce of
the Department of Molecular Biology and The Skaggs Institute
for Chemical Biology at Scripps Research.
Compartments and Scaffolds on the Nano-Scale
Similar to a piece of paper folded into an origami box,
the strand of DNA that Shih and Joyce designed folds into
a compact octahedrona structure consisting of twelve
edges, six vertices, and eight triangular faces. The structure
is about 22 nanometers in overall diameter.
These miniscule octahedral structures are the culmination
of a design process that started one day when Shih was building
a number of shapes with flexible ball and stick models in
the laboratory. This exercise attracted his attention to an
important structural principle: frames built with triangular
faces are rigid, while cubes and other frames built with non-triangular
faces are easily deformed.
Translating this principle to a scale over a million times
smaller, Shih sought to design a DNA sequence that would fold
into a triangle-faced, and therefore very rigid, object. Shih
and Joyce settled on trying to build an octahedron. Shih and
Joyce constructed a 1669-nucleotide strand of DNA that they
designed to have a number of self-complementary regions, which
would induce the strand to fold back on itself to form a sturdy
octahedron. Folding the DNA into the octahedral structures
simply required the heating and then cooling of solutions
containing the DNA, magnesium ions, and a few accessory molecules.
And, indeed, the DNA spontaneously folded into the target
The researchers used cryoelectron microscopy, in collaboration
with Research Assistant Joel Quispe of the Scripps Research
Automated Molecular Imaging Group, to take two-dimensional
snapshots of the octahedral structures. Significantly, the
structures were highly uniform in shapeuniform enough,
in fact, to allow the reconstruction of the three-dimensional
structure by computational averaging of the individual particle
Shih and Joyce note that because all twelve edges of the
octahedral structures have unique sequences, they are versatile
molecular building blocks that could potentially be used to
self-assemble complex higher-order structures.
Possible applications include using these octahedra as artificial
compartments into which proteins or other molecules could
be insertedsomething Joyce likens to a virus in reverse,
since in nature, viruses are self-assembling nanostructures
that typically have proteins on the outside and DNA or RNA
on the inside.
"With this," says Joyce, "you could in principle have DNA
on the outside and proteins on the inside."
The DNA octahedra could possibly form scaffolds that host
proteins for the purposes of x-ray crystallography, which
depends on growing well-ordered crystals composed of arrays
Another potential application is in the area of electronics
and computing. Computers, which rely on the movement and storage
of charges, can potentially be built with nano-scale transistors,
but one of the big challenges to accomplishing this is organizing
these components into integrated circuits. Structures like
the ones that Shih and Joyce have developed might someday
guide the assembly of nanoscale circuits that extend computing
performance beyond the limits set by silicon integrated circuit
The article, "A 1.7-kilobase single-stranded DNA that folds
into a nanoscale octahedron" was authored by William M. Shih,
Joel D. Quispe, and Gerald F. Joyce and appears in the February
12, 2004 issue of the journal Nature.
This work was supported by the National Aeronautics and
Space Administration, The Skaggs Institute for Research, the
National Institutes of Health through the National Center
for Research Resources, and through a Damon Runyon Cancer
Research Foundation fellowship.
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An image of a clonable DNA octahedron,
roughly the size of a small virus, visualized using cryo-electron
microscopy and single-particle reconstruction analysis. False
colors indicate relative electron density. Image
courtesy of Mike Pique.