Nav: Home

Implant acts as a countermeasure

December 16, 2015

ETH Professor Martin Fussenegger calls them molecular prosthetics: cells with specially developed gene circuits that can be implanted into an organism, where they take over metabolic functions that the organism cannot perform itself. Fussenegger and his team at ETH Zurich's Department of Biosystems Science and Engineering in Basel have now succeeded in developing a molecular prosthesis of this kind where the functions are far more complex than before. The prosthesis is tailored to the treatment of psoriasis, a complex and chronic inflammatory disease of the skin.

Gene circuits created in the past typically monitored only whether a metabolic molecule A was present in their environment; if so, they produced a metabolic molecule X as a response. The new, more complex circuit can detect two molecules, A and B, simultaneously, and only if both are present does it produce the molecules X and Y. "We have used cellular components to build an AND logic gate, as is familiar in electronics and without which computers could not function," says Fussenegger. When researchers implanted a circuit with an AND gate of this kind into mice, the circuit was able to successfully suppress phases of psoriasis in the mouse model.

The new molecular prosthesis uses the language by which immune cells in the body communicate with one another: the language of the numerous messenger molecules that the immune cells can both produce and detect.

Prosthesis supports the immune system

The different cells of the immune system are involved in two ways during a psoriasis phase: first, they are responsible for triggering an inflammatory response by increasing the production of various messengers, including those referred to as TNF and IL-22. Second, at a later point, they produce a series of messengers that cause the inflammation to fade away again, among them IL-4 and IL-10.

The circuit developed by the ETH researchers can detect the inflammatory molecules TNF and IL-22. If (and only if) these two messengers are present simultaneously, the circuit produces the anti-inflammatory molecules IL-4 and IL-10. "In this way, our molecular prosthesis helps the immune system to suppress the inflammatory response," explains Fussenegger.

Designer cells in a porous capsule

The scientists took tiny porous capsules made of algal gelatine and encased 200 cells of a human cell line with this gene circuit in each capsule. They then injected 6,000 of these minute capsules into the abdomens of mice. New blood vessels formed naturally and connected the capsules to the bloodstream.

Using a medicine, the scientists triggered an inflammatory response, similar to psoriasis, in the skin of the mice. They then compared the mice into which 'designer cell capsules' had been implanted with those without capsules. Only the latter showed symptoms of inflammation. The implant suppressed the inflammatory disease successfully.

Circuits as an early-warning system

Nowadays, the symptoms of psoriasis - inflamed, itchy and sometimes flaky areas of skin - are usually combated with an ointment that is applied locally. In addition, there are pharmacological having an effect throughout the body.

Therapies of this kind are typically commenced when a phase of psoriasis flares up. "This means that with the existing therapies, we are practically always lagging behind the symptoms," says Fussenegger. The gene circuit implants, on the other hand, lend themselves well to prevention: "The circuit begins producing anti-inflammatory messengers at an early stage - when a phase is looming at the level of inflammatory messengers, instead of waiting until skin rashes appear."

Other inflammatory diseases

The successful experiments in mice were a feasibility study, says Fussenegger. Whether and when designer cells of this kind can be used in humans remains to be seen. However, he says it is conceivable that such cells will one day also be implanted into psoriasis patients. Since growth in connective tissue could cut the implant off from the bloodstream over time, a doctor would probably have to replace it every few months.

Biological circuits of this kind with AND gates may also be suitable for other diseases. Fussenegger says: "Chronic inflammatory diseases are a good example of the type of disease that cannot be diagnosed by measuring a single molecule." However, generally such diseases could be diagnosed using a designer cell that measures the profile of several messengers in the bloodstream. And if this designer cell were also to produce therapeutic molecules, it would open up promising treatment options for a wide range of diseases in the future.
-end-
Reference

Schukur L, Geering B, Charpin-El Hamri G, Fussenegger M: Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis. Science Translational Medicine 2015, 7: 318ra201, doi: 10.1126/scitranslmed.aac4964 [http://dx.doi.org/10.1126/scitranslmed.aac4964]

ETH Zurich

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Moving Forward
When the life you've built slips out of your grasp, you're often told it's best to move on. But is that true? Instead of forgetting the past, TED speakers describe how we can move forward with it. Guests include writers Nora McInerny and Suleika Jaouad, and human rights advocate Lindy Lou Isonhood.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...