"Imagine having a cathedral with all its pieces on the floor, and having all those bricks assemble into a defined structure - this is the kind of idea we can truly foresee with nucleic acids, to assemble these complex structures with molecules," said biochemist and biophysicist Luc Jaeger at the University of California, Santa Barbara.

DNA molecules are best known for carrying the genetic instructions for all organisms, but 25 years ago nucleic-acid-nanotechnology pioneer Ned Seeman of New York University began envisioning another realm of applications for them - as construction blocks, perhaps even in machines.

The result: "DNA machines have been built, as a route to nanorobotics," Seeman told UPI's Nano World. "Nanofacturing of new and revolutionary materials is going to result from some of these devices."

At times, a normally double-stranded DNA molecule can unzip a bit and form a branched version of itself. Seeman foresaw it was possible to weave these branches into three-dimensional structures capable of self-assembly.

To explain, a strand of DNA is made of four bases known, respectively, as A, T, C or G. Each base pairs up with another in a very specific way - A only pairs up with T, and C only pairs up with G, for example. This means any sequence of bases - say ATCG - will only pair up with its complementary sequence - in this case, TAGC.

By synthesizing a double-stranded DNA molecule and unzipping it partially, its branches will stick automatically with complementary sequences on other branched DNA - like a molecular jigsaw puzzle. Mix DNA molecules together the right way and they should assemble into useful structures.

Modern technology allows laboratories to synthesize long strands of DNA at will in any sequence. This means nucleic acids potentially can hold a tremendous amount of information. In turn, scientists in theory can weave extraordinarily complex structures from DNA.

"We can basically create matter that is intimately programmable," Jaeger said.

In addition, nucleic acids "are a really nice material to connect molecules onto, metallic nanoparticles, carbon nanotubes," said chemist Hao Yan of Arizona State University in Tempe.

"Imagine 100 different molecules able to assemble into these intricate architectures, each positioned in an exquisite fashion, each able to be functionalized a different way. You can have this intricate control of the arrangement of matter," Jaeger said.

"If you try to build, say, a box from inorganic stuff, its corners are going to be basically identical. But with DNA, you can have goody type one in corner one, and goody type two in corner two," Seeman said. "You can have all these different functions together."

Nucleic-acid nanotechnology could help organize electronics components together in as soon as "maybe five years," Seeman predicted. "Molecular electronics should be smaller and faster as a consequence of nucleic-acid nanotech."

In time, the hope is to improve nucleic-acid nanotechnology to arrange organic molecules as well. Crystals of DNA could cage molecules that normally do not form into crystals on their own, allowing, for example, X-ray techniques to image their molecular structures - something of critical importance in drug design and other research.

Yan's team is working on a self-assembled DNA array for extraordinarily rapid gene sequencing.

"Imagine having a 1-centimeter array having 1 billion sequencers," he said.

Creating scaffolds for inorganic electronic components or organic molecules comprise in principle the same process, but Seeman cautioned although electronics components such as metal nanoparticles could be 2 nanometers or 3 nanometers wide - or billionths of a meter - the organic molecules researchers would like to encase in DNA crystals are roughly one-tenth of that size.

"The criteria there are more stringent," he said.

Scientists already are creating devices from nucleic acids. In the Dec. 17 issue of the journal Science, Seeman and colleagues revealed they created a device from DNA that mimics the ribosome - the protein factory of the cell - for potential use in developing new synthetic fibers. In the future, they foresee nucleic-acid devices with DNA strands that move in space working as nanorobots.

"Imagine if you have self-assembled arrays from DNA and incorporate robots into them, you can have them all working together, for instance, in a device that could control medical reactions in the body," Yan told Nano World.

"You wouldn't have these DNA robots just running around, but rather as components in nanofactories the same way that on a larger scale you (use) robots to make cars," Seeman clarified.

"Of course, you still need to figure out how to incorporate these self-assembled arrays and nanorobots together," Yan added. "That's a challenging problem."

Nucleic-acid nanotechnology faces a number of other challenges. Scientists largely have conquered the problem of organizing DNA in two dimensions, but moving up to three dimensions remains difficult. DNA also possesses an electrical charge, which can be troublesome when attempting to build nano-sized scaffolds for electronics.

Aside from DNA, scientists are investigating other nucleic acids for use in nanotechnology. For instance, PNA, or peptide nucleic acids, which are designed to mimic DNA, could prove more chemically robust. They also do not possess that troubling charge DNA does. Other nucleic acids include TNA, which uses the sugar threose instead of DNA's deoxyribose.

Jaeger is experimenting with RNA, which in cells helps create proteins. RNA in certain ways is less chemically stable than DNA, but "it has a natural characteristic to be much richer in diversity of these exquisite structures," Jaeger said.

Another potential molecule of interest is LNA, or locked nucleic acids, which mimic RNA instead of DNA.

A critical factor in developing killer applications for nucleic-acid nanotechnology is a method to correct for assembly errors.

"So far, self-assembly happens in the tube, and there are defects in the superstructure when making them. If we move to replicating in large quantities, we have to have error correction, just as in cells in the body," Yan said.

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