Guest Writer - Gastautor - Gast Schrijver

Science and Technology: Nucleic Acid Engineering


The genes in your cells are made up of deoxyribonucleic acid, or DNA: a long, stringy chemical made by fastening together a bunch of small chemical bits like railroad cars in a freight train. The DNA in your cells is actually two of these strings, running side by side. Some of the small chemical bits (called nucleotides) like to stick to certain other bits on the opposite string. DNA has a rather boring structure, but the stickiness of the nucleotides can be used to make far more interesting shapes. In fact, there's a whole field of nanotechnology investigating this, and it may even lead to an early version of molecular manufacturing.

Take a bunch of large wooden beads, some string, some magnets, and some
small patches of hook-and-loop fastener (called velcro when the lawyers aren't watching). Divide the beads into four piles. In the first pile, attach a patch of hooks to each bead. In the second pile, attach a patch of loops. In the third pile, attach a magnet to each bead with the north end facing out. And in the fourth pile, attach a magnet with the south end exposed. Now string together with a random sequence of
beads--for example

1) Hook, Loop, South, Loop, North, North, Hook.If you wanted to make another sequence stick to it, the best pattern
would be:

2) Loop, Hook, North, Hook, South, South, Loop. Any other sequence wouldn't stick as well: a pattern of:

3) North, North, North, South, North, Loop, South
would stick to either of the other strands in only two places.

Make a few dozen strings of each sequence. Now throw them all in a washing machine and turn it on. Wait a few minutes, and you should see that strings 1) and 2) are sticking together, while string 3) doesn't stick to anything. (No, I haven't tried this; but I suspect it would make a great science fair project!)

But we can do more than make the strings stick to each other: we can
make them fold back on themselves. Make a string of:
N, N, N, L, L, L, L, H, H, H, H, S, S, S and throw it in the washer on permanent press, and it should double over.

With a more complex pattern, you could make a cross:NNNN, LLLLHHHH, LNLNSHSH, SSLLNNHH, SSSS The NNNN and SSSS join, and each sequence between the commas doubles over. You get the idea: you can make a lot of different things match up by selecting a sequence from just four letter choices. Accidental
matches of one or two don't matter, because the agitation of the water will pull them apart again. But if enough of them line up, they'll usually stay stuck.

Just like the beads, there are four different kinds of nucleotides in the chain or strand of DNA. Instead of North, South, Hook, and Loop, the nucleotide chemicals are called Adenine, Thiamine, Guanine, and Cytosine, abbreviated A, T, G, and C. Like the beads, A will only stick to T, and G will only stick to C. (You may recognize these letters from the movie GATTACA.) We have machines that can make DNA strands in any desired sequence.

If you tell the machine to make sequences of ACGATCTCGATC andTGCTAGAGCTAG, and then mix them together in water with a little salt, they will pair up. If you make one strand of ACGATCTCGATCGATCGAGATCGT--the first, plus the second backward--it will double over and stick to itself. And so on. (At the molecular scale, things naturally vibrate and bump into each other all the time; you
don't need to throw them in a washing machine to mix them up.)

Chemists have created a huge menu of chemical tricks to play with DNA. They can make one batch of DNA, then make one end of it stick to plastic beads or surfaces. They can attach other molecules or nanoparticles to either end of a strand. They can cut a strand at the location of a certain sequence pattern. They can stir in other DNA sequences in any order they like, letting them attach to the strands. They can attach
additional chemicals to each nucleotide, making the DNA chain stiffer and stronger.

A DNA strand that binds to another but has an end hanging loose can be peeled away by a matching strand. This is enough to build molecular tweezers that open and close. We can watch them work by attaching molecules to the ends that only fluoresce (glow under UV light) when they're close together. A motor that goes around in circles in either direction, in controllable steps, depending on which strands are mixed in next, has also been built.

(The first URL has a neat animation of how the tweezers work.)

Remember that DNA strands can bind to themselves as well as to each other. And you can make several strands with many different sticky sequence patches to make very complex shapes. Just a few months ago, a very clever team managed to build an octahedron out of only one long strand and five short ones. The whole thing is only 22 nanometers wide--about the distance your fingernails grow in half a minute.

So far, this article has been a review of fact. This next part is speculation. If we can build a pre-designed structure, and make it move as we want, we can--in theory, and with enough engineering work--build a molecular robot. The robot would not be very strong, or very fast, and certainly not very big. But it might be able to direct the fabrication of other, more complex devices--things too complex to be built by pure
self-assembly. And there's one good thing about working with molecules:
because they are so small, you can make trillions of them for the price of one. That means that whatever they do can be done by the trillions--perhaps even fast enough to be useful for manufacturing large products such as computer chips. The products would be repetitive, but evenrepetitive chips can be quite valuable for some applications.

Individual control of adjacent robots would allow even more complex systems to be built. And with a molecular-scale DNA robot, it might be possible to guide the fabrication of smaller and stiffer structures, leading eventually to direct mechanical control of chemistry--the ultimate goal of molecular manufacturing.

This has barely scratched the surface of what's being done with DNA engineering. There's also RNA (ribonucleic acid) and PNA (peptide nucleic acid) engineering, and the use of RNA as an enzyme- or antibody-like molecular gripper. Not to mention the recent discovery of RNA interference which has medical and research uses: it can fool a cell into stopping the production of an unwanted protein, by making it think
that that protein's genes came from a virus.

Nucleic acid engineering looks like a good possibility for building a primitive variety of nanorobotics. Such products would be significantly less strong than products built of diamondoid, but are still likely to be useful for a variety of applications. If this technology is developed before diamondoid nanotech, it may provide a gentler
introduction to the power of molecular manufacturing.

Chris has studied nanotechnology and molecular manufacturing for more than a decade. After successful careers in software engineering and dyslexia correction, Chris co-founded the Center for Responsible Nanotechnology in 2002, where he is Director of Research. Chris holds an MS in Computer Science from Stanford University.

Copyright © 2004 Chris Phoenix


Chris Phoenix

CRN Director of Research