Cloaked DNA devices evade the body’s immune system

Researchers from Harvard University's Wyss Institute for Biologically Inspired Engineering have developed a cloaked DNA nanodevice capable of evading the body's immune defenses. The design was inspired by real world viruses and could be used to diagnose cancer and better target treatments to specific areas of tissue.

The researchers used a method known as "DNA origami" to construct the nanoscale device. This method involves folding a long strand of DNA into three-dimensional shapes and programming them to carry molecular instructions to specific cells. In 2012, researchers from Wyss demonstrated the potential of this approach by constructing a barrel-shaped robotic device, loading it with an antibody and programming it to hone in on leukemia and lymphoma cells. Once located, the antibody activated the cells' "suicide switch," causing them to self-destruct through what is known as apoptosis.

While this delivery mechanism could prove useful in treating a variety of diseases, one significant obstacle is that in testing, the nanorobots are quickly digested after being injected into the bloodstream of mice. This led the researchers at Wyss to explore how they could prevent the particles from being chewed up before performing their task.

"We suspected that a virus-like envelope around our particles could solve our problem," says Wyss Institute Core Faculty member and lead author of the study, William Shih, Ph.D.

The team set about replicating a type of virus that protects its genome using a solid protein casing and layer of oily coating. Within this coating is a double layer of phospholipid, a lipid containing phosphate that helps viruses to evade the immune system.

An enveloped virus (left) coats itself with lipid as part of its life cycle. New lipid-coated DNA nanodevices (right) closely resemble those viruses and evade the immune defenses of mice (Image: Steven Perrault/Harvard's Wyss Institute)

In testing the resilience of the nanodevices in the body, the team loaded them with fluorescent dye and injected them into mice, some with the phospholipid coating and some without. The uncoated devices were quickly broken down, with whole-body imaging revealing a concentrated glow in the bladder. Those receiving the coated version showed a full-bodied glow, indicating that the devices remained in the bloodstream for hours after being injected.

The team also observed a link between the presence of the coated nanodevices in the bloodstream and activation of the immune system. Two particular immune-activating molecules were found to be 100-fold lower in mice administered the coated devices as opposed to those given the uncoated versions.

Such manipulation of the immune system could prove beneficial for treating certain conditions, such as activating the immune system to fight cancer cells or conversely, suppressing it to allow transplanted tissue to become established. Despite these potential applications, the researchers are mindful of the potential for adverse effects.

"Activating the immune response could be useful clinically or it might be something to avoid," says Steve Perrault, Ph.D., a Wyss Institute Technology Development fellow. "The main point is that we can control it."

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Cloaked DNA devices evade the body's immune system