Moss Medicines: The Next Revolution in Biotech?

Physcomitrium patens is a species of moss frequently used in applied biotechnology to culture valuable compounds at scale.

Image credit:Britta Rothgänger, ReskiLab, University of Freiburg

Moss is an often-overlooked, ancient plant that is far from insignificant. Among the first to colonize land, mosses greened the planet and transformed Earth’s climate, providing an oxygen-rich atmosphere that allowed animals to evolve.¹ These hardy pioneers can even filter and clean the polluted air of cities.^2,3

Where others see a natural air purifier, Ralf Reskia plant biotechnologist at the University of Freiburg, saw untapped potential in moss. In addition to the range of valuable compounds they produce naturally, Reski believed it made an ideal culture system to grow recombinant human proteins at scale.

Reski first worked on moss as an undergraduate, studying their genetics. He immediately fell in love with the tiny plants, so much so that he asked his supervisor if he could continue working on them for a PhD project. From those early days, his peers quickly dismissed the notion, pointing out that mosses didn’t have to do anything with biotechnology. “You will never become a professor in Germany unless you work with real plants. Nobody is interested in mosses,” Reski recalled the caution from senior professors.

But he persisted. According to Reski, it is much easier to scale up the production of plant cell cultures in general. Mosses, specifically, require no complex media, lack any viruses that are associated with mammalian cell culture systems, and can be grown in large bioreactors in a cost-efficient manner. Over the past several decades, Reski has harnessed the power of moss to produce a variety of beneficial compounds for use in skincare, therapeutics, medical devices, and more.

“I always say that, additionally, (our moss culture systems) are vegan, kosher, halal, whatever you like, because we don’t use any animal products,” he added.

Using Moss to Produce Healthier Oils and Complicated Proteins

In the late 1990s—several years after completing his PhD—Reski convinced his contacts at German chemical company BASF to invest in his moss-focused plant biotechnology endeavors. For one of his first projects, Reski used a genome-wide reverse genetics approach to identify moss genes that are responsible for producing polyunsaturated fatty acids (PUFAs), such as omega-3 and omega-6, which are healthy for humans.⁴ “The idea was to identify such moss genes and then transfer them to ‘real’ plants, to crop plants, to make the oil, for example, more healthy,” Reski explained.

Beyond inserting moss genes into ‘real’ plants, such as rapeseed or canola, Reski was also determined to use mosses as factories to produce therapeutic compounds. With this goal in mind, Reski founded his own company, Greenovation (now Eleva Biologics). Unlike bacterial or yeast culture systems, mosses can produce complex glycosylated proteins that are often needed in biomedical applications. Another attractive feature is that moss species like Physcomitrella open use homologous recombination to repair breaks in DNA, making it ideal for gene insertion.⁵

Because of its favorable glycosylation profile, moss yielded a recombinant version of the human alpha galactosidase protein (aGal), which is used as an enzyme replacement therapy in the treatment of Fabry disease, a rare genetic disease. This moss-aGal protein, the first moss-produced drugentered clinical trials in 2015. It even had a slight competitive edge over its human cell line-produced counterpart when tested in mice; by interacting with a different receptor, it was better able to target the kidney as well as the heart.⁶

Despite the success of moss-aGal, academic and industry peers often asked Reski if moss could make larger, more glycosylated proteins. “So we thought, ‘What is the most complicated human protein that is on the market?’,” he said. The answer was factor H, a protein found in the blood that regulates immune responses and is involved in a range of diseases.⁷

This daring venture turned out to be more fruitful than any of Reski’s team had anticipated—only when writing up their first manuscript about producing the protein in moss did they realise that no other team had successfully brought a recombinant factor H to market.

“People had started trying to make it in yeast, but there were issues with glycosylation, and it cannot be made by (Chinese hamster ovary) cells at the moment, because it’s so complicated,” Reski explained. Moss-produced factor H is currently being investigated in the treatment of age-related macular degeneration and complement disorders such as renal diseases by Reski and his colleagues at Eleva and the University of Freiburg.^8,9

Moss-Made Spider Silk for Biomedicine and Active Compounds in Skincare

These examples wouldn’t be the only times that mosses won out over other culture systems. Reski’s lab recently reported the successful production of a key component of dragline silk from the western black widow spider, a fiber prized for its strength and elasticity.¹⁰ Reski said his moss-made spider silk protein is “more complex than other plant-made spider silks at the moment, so we are now evaluating if we can use it for biomedicine as well.”

Because spider silk proteins don’t provoke immune responses in humans, they are attractive materials for a range of biomedical applications.¹⁰ Reski hopes to put his moss-produced proteins to work in microneedle drug delivery patches.

Outside of the medical field, Reski’s moss factories are also being used in the production of bioactive compounds for skincare and cosmetics. “(In moss) you have a lot of substances which activate genes and the renewal of cells,” Reski said.

However, the virtues of moss go far beyond skincare and medicine, and Reski is passionate about all of them. Peat mosses, for example, regulate Earth’s carbon cycle; increasingly threatened by drainage, land clearing, peat extraction, and increasing temperatures, peat bogs need all the help they can get. “All peatlands together store more carbon than all living matter together, and this is underrated,” Reski said. Reski and his team are currently growing high-performing peat moss clones that can be used to supplement existing peat bogs that are under threat.

Reski’s lab has also explored the effects of climate change on Takakiaa living fossil moss species that is 400 million years old.¹¹ According to Reski, the story of Takakia is a warning about our future. “It saw the dinosaurs coming and going,” he said. “It saw us coming, and if we are not careful, it will see us going.”