DNA-tangling molecule could revolutionize treatments for cancer and HIV

Some of the most deadly human diseases work by worming their way inside your DNA, attaching themselves to the cell's chromosomes. This makes them almost impossible to remove. But a new molecule designed to bamboozle rogue DNA could change everything.

The HIV virus is a good example of how cells can be damaged at the DNA level. Once the virus binds itself to a cell, it injects RNA and the enzymes necessary to create double-stranded DNA, which can then be integrated into one of the chromosomes of the host cell. This parasitic DNA can then lie dormant until it's ready to start building new viruses, creating an almost impregnable beachhead inside the body to continue the infection process.

DNA-tangling molecule could revolutionize treatments for cancer and HIV

Researchers at the University of Texas, led by chemistry professor Brent Iverson, wanted to beat the rogue DNA at its own game. So they've started working on molecules that can bind with specific DNA so that that part of the double helix becomes tangled, making it unable to carry out any genetic functions. Their molecule, which has been given the rather nifty name of "threading tetra-intercalator", can silence a strand of DNA for up to 16 days, before the helix finally untwists itself. You can see a diagram of how the molecule works on the left.

This breakthrough opens up the possibility of drug treatments specifically targeted to keep the rogue DNA created by HIV, cancer, and other genetic diseases silenced, potentially on a permanent basis. That particular application is still a ways off, but this result suggests it's a very real possibility. In a statement, Iverson explains how the molecule works:

"If you think of DNA as a spiral staircase, 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. Our off-rate under the conditions we used is the slowest we know of by a wide margin. Take HIV, for example. 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."

Fellow researcher Amy Rhoden-Smith provides some more technical details on how the base molecule, naphthalenetetracarboxylic diimide (NDI), can be adapted to silence the desired strain of rogue DNA. Basically, it's the molecular equivalent of building with Lego:

"It's pretty simple for us to make. We are able to grow the chain of NDIs from special resin beads. We run reactions right on the beads, attach pieces in the proper order and keep growing the molecules until we are ready to cleave them off. It's mostly automated at this point. "The larger molecule is composed of little pieces that bind to short segments of DNA, kind of like the way Legos fit together," she says. "The little pieces can bind different sequences, and we can put them together in different ways. We can put the Legos in a different arrangement. Then we scan for sequences that they'll bind."

Via Nature Chemistry. Top image by zentilia, via Shutterstock. Diagram by Brent Iverson.