For their second trick, the researchers introduced a single base-pair mismatch into the DNA so that, for example, a C was paired up with an A (rather than its normal partner, G). This tweak boosted the molecule’s resistance some 300-fold, probably because it distorts the double helical structure. They could do this easily by connecting only one of DNA’s two strands into the circuit. The second strand - which can either be a perfect match to the first or contain a mismatch - can lift on or off.
Showing the electrical effect of such sequence mismatch and enzyme cutting is the real strength of the experiments, says Danny Porath, of Hebrew University, in Jerusalem, Israel, who has also measured current through DNA. “They play with the parameters and show that conductivity of DNA clearly depends on them, and that’s beautiful,” he says.
Nuckolls is now working to exploit this discovery to detect single nucleotide polymorphisms (SNPs), the one-letter variations in DNA that are linked to, for example, susceptibility to Alzheimer’s, diabetes, and many other major diseases. Nuckolls hopes that his method can be used to identify SNPs more rapidly and with greater sensitivity than existing methods. In such a device, a reference strand of DNA is wired into the circuit and other strands allowed to pair up with it. If the second strand carries a different base at the position of the SNP, this would be enough to trigger a change in the current through a nanoscale circuit, just as the base-pair mismatch did. Nuckolls says that he is already working with electrical engineers to create a sensor that can slot into existing semiconductor chips, making it cheap and readily available. “It’s one of our big focuses, and we’re pretty close,” he says.
The team is likely to have competition. Late last year, a group led by Wonbong Choi, of Florida International University, in Miami, reported that it had strung 80 base pairs of DNA between two carbon nanotubes and sent current through the DNA. Choi says that he is working to create a sensor that can rapidly reveal the presence of specific genetic sequences–such as the avian influenza virus–by looking at changes in current through the tiny circuit.
Barton, meanwhile, is intent on finding out whether the conductivity of DNA serves any biological purpose in the cell. She has evidence that proteins bound to DNA may detect DNA damage by changes in its electrical properties, perhaps triggering repair of the damage. “We think it’s something nature takes advantage of,” she says. “It’s a radical idea, but I think as we get more and more evidence, the case will be built.”