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Nanorobot Detects Cancer

February 26, 2012


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.

  1. February 27, 2012 3:24 pm

    Cheering and chilling both–Greg Bear’s “Blood Music” comes to mind–and a few other sf writers that don’t share your gentle approach to the wild and woolly future, Joan. And I can’t help but notice that your big leap forward in nanotech is not in Materials or Computers, but in DNA–absolutely the most dangerous thing to muck with–not that the anticancer-apps that you describe sound all that dangerous (tho how would I know?) but your analogy about the Plastic PC that counts to 7 (well-done! to your fourth grade self, by the way.) is pretty scary.
    I’ve experienced sci-fi stories that look at DNA from the context of communication and memory storage, from the context of conscious control of DNA, from the context of hacker ‘viruses’ that infect our minds, rather than our bodies, and on and on. Just the sheer variety of nightmare scenarios on the subject tells me that it’s real-world affects will both benefit and potentially destroy civilization–not saying there’s anything wrong with it, mind you, it’s just a little scary…

    • February 27, 2012 8:54 pm

      Not sure “gentle” applies–the microbes in Brain Plague turn people into vampires, or worse.
      The PC viruses so far have caused more of an IT headache than anything. One thing to remember, in classic biology theory the “parasites” have to consume a small fraction of the overall resources, otherwise their host or prey goes extinct and the parasite with them. So I think it’s reasonable to expect that nanorobots will always depend on a supply of healthy hosts.

  2. February 27, 2012 8:53 pm

    Neat! Of course, the price per dose will have to come down a bit to get from cool to useful. Medicines like would probably be in the $100,000 per dose range, at a guess.

    • February 27, 2012 8:57 pm

      Well that’s how the human genome started out (millions of $$ for the first one) but now it’s down to $1,000.

      The neat thing about DNA origami is that you can do it all, in principle, with (1) a simple program to predict the sequence; (2) a DNA synthesizer. Of course, human development and testing is expensive, but eventually this kind of tech has the potential to be super cheap.

  3. Alex Tolley permalink
    February 28, 2012 10:19 am

    While the technology is very neat, I don’t see it as being more than a demonstration of the technology. (Whenever fancy technology is offered up, it is pressed into some humanitarian role, even if unsuitable for the task).

    As heteromeles says, the price per dose is likely to be very high. Thhe reason should be clear – the manufacturing complexity and quality control will be very problematic.

    I also see practical problems.

    1. What happens to the bot that attaches to one target only? Does it just sit on teh site indefinitely – inert, or is it a time bomb waiting to go off when the second lock is broken?

    2. Is foreign DNA not going to invoke an immune response in the patient as it circulates in the blood stream?

    3. Is the DNA container resistant to biological degradation as it seeks out targets? What sort of damage can it sustain without releasing its payload and yet still function at the target site?

    4. How will it penetrate solid tumors?

    There must be a lot of problems that I haven’t covered that would make this an unlikely therapeutic approach.

    • February 28, 2012 10:40 am

      You’re right there are problems–though not so much more than for drugs we take regularly. Cancer and AIDS drugs have all sorts of serious complications.

      With respect to your good questions, as far as I can tell (the paper authors would know better):

      (1) The bot that attaches one target does nothing.

      (2) Immune response to DNA is unlikely, because our bodies have to accept all kinds of DNA sequences within our cells. There is a serious disorder, lupus, in which DNA may induce antibodies.

      (3) DNA containers are highly stable, because of the double helix. The cytosines do degrade to uracil; not sure of the time scale. That’s unlikely to undo the helical part.

      (4) The bot can penetrate anywhere blood cells can go; it’s very tiny, about the size of a ribosome. The cases shown in the article were mostly blood cell cancers. However, tumor blood vessels are leaky, so I would guess that penetration is possible.

      • Alex Tolley permalink
        February 28, 2012 11:57 am

        The bot that attaches one target does nothing.
        So it just sits on the cell surface inert, indefinitely? I find that hard to believe. More likely it degrades and releases its drug payload at some time in the future. If you used te technology for different cancers, wouldn’t you end up with lots of “inert” bots holding a payload that just get released when the local cell dies?

        Immune response to DNA is unlikely, because our bodies have to accept all kinds of DNA sequences within our cells
        That might imply that viruses do not need a protein coat to wrap their DNA/RNA. We could test this very simply by injecting naked DNA into a test mammal and see what happens. This reference suggests cells can destroy foreign DNA within them and I suspect that similar mechanisms do this for foreign DNA outside of cells.

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