Once the researchers had synthesized stable, super-sized nucleotides, they used commercially available equipment to link them together into DNA sequences. Natural DNA needs approximately 10.5 paired nucleotide “steps” to make one full rotation in the double helix. The enlarged bases increase the diameter of the helix, which needs more such steps as a result. Being larger, the molecular structure offers increased stability; while natural DNA in Kool’s lab fell apart at 21C, xDNA remained intact up to 56C. Kool’s research “shows that the double helical structure of [natural] DNA does not have to be the only one,” says Danith Ly, an assistant chemistry professor at Carnegie Mellon University and an expert in developing chemical tools for studying genomics and proteomics.Kool’s ultimate quest for a tailor-made genetic system is a tall order-and not one to be rushed, says Ly: “In order for a biological function to exist independent of anything, it needs proteins, lipids, enzymes-all sorts of things. For us to do it in the next hundred years might be possible, but it would be difficult.” And before that, Kool must create expanded versions of the G and C bases, which will likely be comparable in difficulty to his work on xA and xT.
Science fiction scenarios of designer genes aside, Kool believes xDNA has practical implication in diagnostics-particularly in improving the existing medical procedures that detect health conditions based on the structure of a person’s DNA. Clinicians looking for particular DNA or RNA in a person take a tissue sample and introduce an artificial DNA strand that will bond to that material. Techniques that wash away everything but bound pairs containing the artificial DNA allow labs to readily search what is left. “If it doesn’t bind properly, you know that it either a mutation or the [sought] DNA isn’t there,” says Paul Billings, vice president and national director of genetics and genomics at Laboratory Corporation of America, a diagnostics testing company in Burlington, NC.
Because xDNA bonds more strongly than regular DNA, it would be more resilient in this testing process. Moreover, its natural fluorescence could act as a beacon, making detection easier. Even after the technique was more than a lab curiosity, however, its diagnostic utility would have to be demonstrated in the field. “First of all, you have to prove that it gets into the cells and behaves in other ways as other DNA,” Billings says. “Second, you have to prove that it’s better than other methods.” There are well-established methods that work now, and no evidence yet that the binding and fluorescent properties of xDNA would be a clear improvement.
Furthermore, the fluorescent characteristics of xDNA would likely need adjusting, says Ly. According to the paper by Kool’s team, the molecule lit up when illuminated by ultraviolet light with a wavelength of about 390 nanometers. “Tissues do not absorb very well at these wavelengths,” Ly notes, suggesting that for diagnostics use, the base would have to be adjusted to respond to light that was closer to the red end of the spectrum. But, according to Kool, this would not necessarily pose a significant problem in examinations of sufficiently thin slices of tissue. In fact, xDNA nucleotides may even change their fluorescent color or intensity when bonding to natural DNA or RNA-a phenomenon that would add more possible tools to the diagnostics kit. Call it a big light for medical workers.