Someday, popping a pill after you've become sick may seem like a thing of the past. Scientists have just genetically retooled human cells to act as micro disease sentries and drug factories inside the body. The cells constantly monitor for a specific disease and then produce anti-inflammatory drugs at the moment they're needed.

We can enable the body to prevent diseases and design a world of new molecular prosthetics

For the new research that appears this week in the journal Science Translational Medicine, the disease in question was psoriasis, a little-understood genetic ailment in which the immune system attacks healthy skin cells, causing itchy, scaly patches. In a remarkable feat of genetic engineering, a team of bioengineers led by Martin Fussenegger at the Swiss Federal Institute of Technology reprogrammed living cells to identify these psoriasis flareups and manufacture a suite of therapeutic drugs in response. When implanted into mice with psoriasis, these cells effectively halted the autoimmune disease in its tracks, allowing skin to re-heal.

"Our cells have been engineered to sense two input signals that are characteristic [of an] immune system ramping up [to fight] a psoriasis flare-up. When that's been detected by these designer cells, they mount an immediate reaction by delivering [anti-inflammatory drugs], as if the flare-up had not even developed," Fussenegger says.

Cell Sentries

Fussenegger's re-engineered human cells are called cytokine converters. To make them, the researchers first fitted cells with two new types of chemical receptors on their surface. These extra receptors allowed the cells to identify when a pair of specific proteins was floating around them. Those proteins, called tumor necrosis factor (TNF) and interleukin-22 (IL-22). individually play vital roles in the immune system, but when found together, they are known to be the hallmark of a psoriasis flare-up.

Schematic of the AND-gate-specific cytokine converter–based psoriasis treatment. Schukur et al., Science Translational Medicine (2015)

Next, Fussenegger programmed the cells so that if they identified both of these molecules at the same time, they would respond by crafting a pair of anti-inflammatory molecules, called IL4 and IL10, and flood the bloodstream with them. Previous studies had already identified the IL4 and IL10 molecules as effective medicines at halting and healing bouts of acute psoriasis.

For Fussenegger's mice, a single injection of the altered human cells could keep psoriasis at bay for weeks. In effect, Fussenegger's cells acted like ever-watchful sentinels, constantly monitoring for the right time to apply their medicines.

The Future of Medicine

You may be wondering, why bother with these genetically engineered cells when you can treat patents directly with IL4 and IL10? "That's been tested in clinical trials, but the issue is these molecules degrade in the bloodstream far, far too quickly. You essentially would have to constantly inject them into a patient for the desired effect," Fussenegger says.

While Fussenegger and his colleagues have yet to start human trials, preliminary research found that their synthetic cells act almost identically while in human blood. In fact, Fussenegger believes that not too far in the future, researchers will be able to use this type of research as the basis of a gene therapy. It would work like this: A doctor could take a cell sample directly from a patient with psoriasis, genetically alter those cells in the lab just like Fussenegger showed today, and inject the new cells into a patch under the skin, where they could immediately get to work and be ready whenever needed.

"We're designing cells that bring new functions and control opportunities into the body. I think the question is not whether we implement this type of technology, but when we will implement it," says Fussenegger. "With this type of technology we can enable the body to prevent diseases and design a world of new molecular prosthetics. Yes, I believe this is part of the future of medicine."

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