Chemists at The University of Texas at Austin have created a molecule that’s so good at tangling itself inside the double helix of a DNA sequence that it can stay there for up to 16 days before the DNA liberates itself, much longer than any other molecule reported.
It’s an important step along the path to someday creating drugs that can go after rogue DNA directly. Such drugs would be revolutionary in the treatment of genetic diseases, cancer or retroviruses such as HIV, which incorporate viral DNA directly into the body’s DNA.
“If you think of DNA as a spiral staircase,” says Brent Iverson, professor of chemistry and chair of the department of chemistry and biochemistry, “imagine sliding something between the steps. That’s what our molecule does. It can be visualized as binding to DNA in the same way a snake might climb a ladder. It goes back and forth through the central staircase with sections of it between the steps. Once in, it takes a long time to get loose.” Iverson says the goal is to be able to directly turn on or off a particular sequence of genes.
“Take HIV, for example,” he says. “We want to be able to track it to wherever it is in the chromosome and just sit on it and keep it quiet. Right now we treat HIV at a much later stage with drugs such as the protease inhibitors, but at the end of the day, the HIV DNA is still there. This would be a way to silence that stuff at its source.” Iverson, whose results were published in September in Nature Chemistry, strongly cautions that there are numerous obstacles to overcome before such treatments could become available.
The hypothetical drug would have to be able to get into cells and hunt down a long and specific DNA sequence in the right region of our genome. It would have to be able to bind to that sequence and stay there long enough to be therapeutically meaningful.