For decades, Chinese hamster ovary (CHO) cells have been the gold standard for producing biologic drugs, from monoclonal antibodies to enzyme therapies. But for some of the most complex and fragile proteins, even CHO systems can fall short. Now, an unlikely contender—moss—is offering a new path forward.
At Germany-based Eleva, researchers are using Physcomitrium patens, a simple moss species, as a suspension cell culture system for producing recombinant human proteins that are difficult and sometimes impossible to manufacture in conventional platforms. According to Andreas Schaaf, PhD, Eleva’s CSO, these include “glycoproteins with complex or sensitive glycosylation requirements,” as well as cytokines, immune-cytokines, complement regulators, enzymes for rare metabolic disorders, and advanced antibody formats such as antibody-toxin conjugates.
The technology has deep academic roots. Plant biotechnologist Ralf Reski, PhD, at the University of Freiburg, helped develop P. patens into a model species for synthetic and systems biology and co-invented the moss bioreactor. His research led to the founding of Greenovation, now known as Eleva, which has since advanced the platform toward clinical-stage drug development.
The company’s first moss-produced drug candidate to enter clinical studies was a recombinant alpha-galactosidase enzyme replacement therapy (ERT) for Fabry disease, a rare lysosomal storage disorder. Current ERT options for Fabry patients are limited by short circulating half-life, inefficient uptake into key affected cell types, and immunogenicity. Eleva believes the more uniform glycosylation achieved through moss production could help overcome these limitations.
A particularly significant demonstration of the platform is Eleva’s recombinant complement Factor H candidate, currently in Phase Ib. Factor H is a large complement-regulatory glycoprotein used to target complement-related renal diseases such as C3 glomerulopathy (C3G), lupus nephritis (LN), and potentially dry age-related macular degeneration (AMD).
Schaaf notes that Factor H “had long resisted reliable expression in conventional systems such as yeast or CHO cells.” For patients with C3G—many of whom are young and face a 50% rate of kidney failure within ten years—the ability to restore natural Factor H activity could represent a major therapeutic shift. Current treatments often rely on broader complement suppression and carry boxed warnings for serious infections.
So why moss?
Unlike mammalian cells, which often generate heterogeneous glycan mixtures, moss produces more uniform glycosylation profiles due to its simplified glycan-processing pathway. This matters because glycosylation can directly affect a drug’s stability, efficacy, and immunogenicity.
Moss cells are also largely unaffected by toxic cytokine feedback, which in mammalian systems can inhibit growth or trigger apoptosis, limiting secretion efficiency and yields. Plant-specific chaperones and folding assistants, including protein disulfide isomerases, also help prevent protein aggregation and support the correct assembly of complex multimeric proteins.
“Moss offers clear advantages over other expression systems for certain protein classes that are difficult or impossible to manufacture otherwise,” Schaaf says, adding that such therapies might otherwise be “deprioritized or abandoned.”
There are practical manufacturing advantages, too. Moss requires no animal-derived media supplements, eliminating mammalian virus risk and removing the need for costly viral filtration in downstream processing. It is also less sensitive to fluctuations in temperature and pH, giving manufacturers greater process flexibility and potentially lowering production costs.
Still, Eleva is careful not to position moss as a replacement for CHO. Björn Cochlovius, PhD, CEO of Eleva, says standard proteins will continue to be best served by established systems. “The goal is not to replace CHO or other systems with moss when those other systems deliver well,” he explains.
Instead, the aim is to ensure that the range of therapeutic candidates in development is not defined by the limits of existing manufacturing platforms. Yields for large-scale GMP production and improving predictability remain ongoing challenges, but commercially viable titers are already being achieved through continuous optimization.
Cochlovius believes regulatory precedent and growing CDMO partnerships will further strengthen adoption. “A moss-based platform capable of reliably producing this category of proteins at scale would open a pipeline of programs that are currently inaccessible,” he says.
For biotech developers—and for patients with limited treatment options—that could make all the difference. Sometimes, the future of medicine grows in the smallest places.
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