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Nano-Origami: Scientists at Scripps Research Create Single, Clonable Strand
of DNA That Folds into an Octahedron
La Jolla, CA, February 11, 2004 - 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
ribosome.
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 of tomorrow.
"Now we have biological control, and not just synthetic chemical
control, over the production of rigid, wireframe DNA objects," says Research
Associate William Shih, Ph.D., of Scripps Research.
Shih led the research, described in the latest issue of the
journal Nature, with Professor Gerald Joyce, M.D., Ph.D., 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 octahedron - a 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 structure.
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 shape - uniform enough,
in fact, to allow the reconstruction of the three-dimensional structure by computational
averaging of the individual particle images.
Potential Applications
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 inserted - something
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 of molecules.
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 technology.
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.
About The Scripps Research Institute
The Scripps Research Institute in La Jolla, California, is one of the world's
largest, private, non-profit biomedical research organizations. It stands at
the forefront of basic biomedical science that seeks to comprehend the most fundamental
processes of life. Scripps Research is internationally recognized for its research
into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune
diseases, cardiovascular diseases and synthetic vaccine development.
For more information contact:
Keith McKeown
10550 North Torrey Pines Road
La Jolla, California 92037
Tel: 858.784.8134
Fax: 858.784.8118
kmckeown@scripps.edu
Copyright © 2004 TSRI.
All rights reserved. Reproduction in whole or in part in any form or medium without express written permission of TSRI is prohibited.
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