DNA Nanobots Can Fool the Immune System by Disguising Themselves as Viruses

Scientists took a cue from the one of the most efficient genetic-code delivery systems in history or biology.

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Apr 23 2014, 8:27pm

Sometimes to help the body, you have to fool the body, which is why researchers from Harvard's Wyss Institute of Biologically Inspired Engineering modeled their latest DNA nanodevice after those great immune-system evaders, viruses.

The whole project, outlined in a new paper published at ACS Nano, is pretty bizarre and cool—back in February 2012, researchers at Wyss announced that they had developed a robotic device fashioned out of DNA. They described how one day the tiny devices could be used for targeting specific, undesirable cells within the body.

The DNAbots were shaped like an open barrel whose two halves are closed by a hinge. When the barrel rolls across, say, a leukemia or lymphoma cell, the special DNA latches could recognize the cell-surface proteins, and the two halves of the barrel could swing open to deliver the DNAbot's payload, which could include molecules with encoded instructions that would interact with specific cell surface signaling receptors, all to give the cells the order to self-destruct. That's the idea, anyway.

The approach was already modeled on the seek-and-destroy methods of our body's own white blood cells. However, rather than being flattered by the mimicry, the immune system reacted to the DNA bots in a pretty hostile manner when they were injected into mice. When researchers covered the bots in fluorescent dye and injected them into the rodents' bloodstreams, the bots showed up glowing in their bladders pretty quickly. They were getting caught, filtered, and marked for expulsion.

"That led us to ask, 'How could we protect our particles from getting chewed up?'" according to Wyss Institute Core Faculty member, William Shih.

 

The solution was to model the DNA bots after something that had more experience fooling the immune system. So the white blood cell-inspired DNA nanodevices got a virus-inspired cloaking device. They enclosed the nanodevices in a solid protein case. The researchers then made tiny DNA handles upon which they could hang lipids to create an oily coating like the kind that viruses use to evade the immune system. The result was a very virus-like DNAbot.

Image: Steven Perrault/Harvard's Wyss Institute

When the coated nanodevices were injected into mice, their whole little bodies were glowing for hours, indicating that the nanodevices were sticking around as long as effective drugs do.

DNA is a natural biocompatible and biodegradable material, which gives DNA nanotechnology a widely recognized potential as a delivery mechanism for drugs and molecular signals. Researchers are learning how to better program DNA-based nanodevices that could one day help the body more effectively fight disease. There's something almost poetic about how a nanodevice mimics its target in order to more effectively fight it. It's maybe not as viscerally thrilling as a cheetah-robot running faster than Usain Bolt, but it's also not as unnerving as one modeled after a blue sea slug.

Credit: Steven Perrault/Harvard's Wyss Institute