Stephen Levy

April 23, 2014

3 Min Read
DNA Nanodevices Sneak Past Mouse Immune Systems

nano DNA

A natural virus (left) and a lipid-coated DNA nanodevice (right) created by the researchers. (Courtesy Steven Perrault/Harvard's Wyss Institute)

Scientists at Harvard's Wyss Institute for Biologically Inspired Engineering have built the first DNA nanodevices that survive the body's immune system.

This is significant because, although researchers have known for some time that it's possible to use DNA as a building block to make nanodevices that can target pathogens, getting those structures past the body's natural defenses has been a problem.

In "Virus-Inspired Membrane Encapsulation of DNA Nanostructures To Achieve In Vivo Stability," published in the ACS Nano journal, the research team describes how they engineered a coating that essentially renders their DNA nanodevices invisible to the body's immune system.

The research team was led by Wyss Institute Core Faculty member William Shih, PhD, associate professor of biological chemistry and molecular pharmacology at Harvard Medical School, associate professor of cancer biology at the Dana-Farber Cancer Institute, and the paper's senior author. "We're mimicking virus functionality to eventually build therapeutics that specifically target cells," Shih told ScienceDaily.

To build their stealth nanodevice, the scientists used DNA origami techniques that Shih had previously helped pioneer. A long strand of DNA was programmed to fold into a virus-sized octahedron, then loaded with fluorescent dye so it could be tracked within the mouse's body.

In mice that received the uncoated octahedron nanodevices, just the bladder glowed. This meant that the animals had broken down the DNA quickly and the remainder was ready to be excreted.

"We suspected that a virus-like envelope around our particles could solve our problem," Shih said. That envelope, the researchers theorized, might help the DNA to evade the immune system.

Then Steve Perrault, PhD, a Wyss Institute Technology Development fellow and the paper's lead author, built handles onto the octahedrons on which to hang lipids. Those handles directed the assembly of a single bilayer membrane of a phospholipid encapsulating the octahedron.

Refresh your medical device industry knowledge at MD&M East, June 9-12, 2014 in New York City.

When they were injected with the new coated nanodevices, the whole bodies of the mice glowed for hours. This showed that nanodevices remained in the bloodstream as long as an actual drug might. The researchers also found that the coated devices were not triggering an immune response. Levels of two immune-activating molecules were at least 100 times lower in mice treated with coated nanodevices than in those that got uncoated nanodevices, they reported

"Activating the immune response could be useful clinically or it might be something to avoid," Perrault said. "The main point is that we can control it."

Stephen Levy is a contributor to Qmed and MPMN.

Sign up for the QMED & MD+DI Daily newsletter.

You May Also Like