On ResearchGate: Scientists turn plant cells into efficient pharmaceutical factories

Take a look how one molecular plant biologist and his team are using the network to shape the future of vaccine production.

For the first time, researchers have developed a plant-based way to make pharmaceutical proteins that offers both rapid production and highly controlled conditions. Plant-cell packs, affectionately dubbed “cookies” by the researchers who work with them, can express multiple genes in just a few days. The technology could facilitate everything from emergency vaccine production to personalized medicine, a rapidly growing industry that needs the safety and flexibility the cookies offer in order to scale.

Plants as protein factories

Other methods for plant-produced proteins came into the spotlight?during the Ebola crisis, when greenhouses full of plants churned out antibodies for an experimental vaccine. That process involves injecting bacteria carrying specific genes into the leaf of a plant, which then manufactures the desired protein. Efforts are underway to produce other pharmaceuticals, like?flu vaccines, with similar methods, but the practice has yet to become truly widespread. While using plants is faster than more traditional methods relying on animal cells, it has drawbacks too. For one, it’s not completely sterile. “Avoiding dirt and microbes altogether is something you can’t really do with a leaf-based system,” explains plant molecular biologist?Markus Sack. Another issue is that delicate plants pose a challenge for automation, as robots lack humans’ sensitive touch and tend to damage the leaves.

Photo Credit: Fraunhofer IME

To address both sterility and handling issues, some researchers and manufacturers use plant cells suspended in liquid rather than actual plants. However, this approach produces proteins in much lower quantities—a real limitation. That’s where the “cookies” come in. Developed in Germany at the Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), they provide the same potential for sterile, controlled conditions as liquid suspension, with massively boosted efficiency.

The best of both worlds

Like many scientific innovations, the invention of the cookie technology involved an element of chance. While using plant cells suspended in liquid, IME researcher Thomas Rademacher noticed some of his cells were expressing a red florescent protein at higher levels than one would expect. That led to a series of experiments, and eventually a counter-intuitive conclusion: plant cell suspension works better when the liquid nutrient medium is removed. Rademacher harvested cells from the liquid to form a round disc, and the “cookie” technology was born. Now, the researchers are pursuing funding for the project and conducting workshops with labs around the world.

“I was blown away,” said?Ed Rybicki, Director of the University of Cape Town’s Biopharming Research Unit and one of the first researchers outside the IME group to try the technology. “This was such a simple, yet such a potentially powerful technique. I think the impact will be large, and we certainly intend to use several of the applications in my research group.”

Photo Credit: Ingo Appelhagen (John Innes Centre)

The cookie technique could have applications far beyond vaccines. For example, because they can express many genes simultaneously, cookies could one day be used to develop personalized medicines and facilitate advances in synthetic biology. In academic settings, the plant-cell disks won’t completely replace actual plants, which are easier to work with. “Plants are a bit more robust, and you see immediately if a plant is happy. With the suspension cells, you need more experience to see if something’s wrong,” says Sack. “But when it comes to really manufacturing and selling a product, suspension cells offer a lot of advantages.”

One of those advantages is cost. “Speeding up production is of course related to the final cost, which is not trivial when you plan to commercialize the process,” explains plant biologist?Robert Malinowski?of the Polish Academy of Sciences, who first heard about the cookie technology at a conference. He’s optimistic that cookies could help make plant-based antibody production cheap enough to compete with existing commercial techniques.

The IME researchers have applied for a patent, and plan to publish their results soon. “In the meantime, we are keen on spreading the word, so people have an opportunity to follow the developments and ask questions,” said Sack. “I really think this can contribute to speeding up biotechnology developments and even open up completely new areas. The possibilities are endless.”

To learn more about plant-cell pack technology, visit?Sack's project on ResearchGate.