We recently discussed how DNA construction, also known as “DNA origami” can be used to build all kinds of nano-scale structures whose folded shape is determined by the DNA sequence. Now in Science we see a report from George Church’s lab of a cancer-detecting nanorobot made from DNA origami. This is the first I’ve seen of a nanorobot that could actually do the kinds of things seen in Brain Plague and The Highest Frontier.
The nanorobot–made out of self-folded DNA–consists of a hinged box that shuts to form a container with a hexagonal cross-section. Within the box is a protein payload (lavender), in this case a protein that fluoresces once exposed. But the box is “locked” shut by two locks, consisting of “aptamers,” short DNA chains (blue) that can recognize specific molecules on the surface of a cell. When the lid shuts, each aptamer clamp “locks” it by base-pairing with a complementary chain (orange). So the box has two “locks,” either of which keeps it shut.
But each aptamer also can bind to a specific cell-surface protein found on a cancer cell. Different cancer cells have different combinations of cell-surface proteins, so a detector needs to “read” their combination.
How does the “logic” work? Each of the two aptamers on the box recognizes a different protein (the “key” to the aptamer “lock”). The aptamer-complement bond can open briefly in solution, in equilibrium. When the open aptamer binds the “key” protein, it gets stuck (thermodynamically) and no longer comes off to join its complement on the box. If (and only if) the cancer cell possesses both types of protein, then both aptamer locks will stay open simultaneously. The box then flies open and exposes its fluorescent reporter. Finally, it binds to an anti-cancer acting cell such as a natural killer cell.
The nanorobots can distinguish among six different types of cancer cell. Pretty impressive. It reminds me of a plastic computer I built back in fourth grade, which could count from 0 to 7. That was quite a while ago. Imagine what these nanorobots will be up to half a century from now.