Tag: Germany

In a new study published in Cell titled, “RegVelo: gene-regulatory-informed dynamics of single cells,” researchers from Stowers Institute of Medical Research have developed a new AI model that connects two areas of single-cell biology that have often remained separate: estimating how cells change over time and inferring the gene regulatory networks controlling those changes.  

“You can imagine if you had a very early set of cells, having a particular set of instructions could allow you to reproduce, in vitro, some of these cell types in a very natural way. These cells could then be used in cell therapies in regenerative medicine,” said Tatjana Sauka-Spengler, PhD, Stowers Institute Investigator and co-senior author of the study.  

While development is often described as a series of static snapshots of cell states, RegVelo models how these fate decisions are encoded in gene regulatory networks over time and space, and what drives cell state transitions. In zebrafish neural crest development, RegVelo identified an early driver of pigment cell formation (tfec) and revealed a previously unknown regulator of pigment cell fate (elf1). The neural crest is a developmental system that gives rise to many different cell types, including pigment cells, craniofacial tissues, and parts of the peripheral nervous system. 

CRISPR/Cas9-mediated knockout and single-cell Perturb-seq supported predictions, showing that the model could do more than describe developmental changes and generate biologically meaningful hypotheses that held up in living systems. 

Alejandro Sánchez Alvarado, PhD, Stowers President and chief scientific officer says RegVelo’s value “extends well beyond” neural crest cells and is applicable to any system in which cells change over time, from basic developmental biology to modeling tumor trajectories and the cellular outcomes that may inform treatment. 

“Sauka-Spengler and her collaborators have developed a meaningfully different way to process this kind of data,” said Sánchez Alvarado. “It allows us to infer the most likely path of each component through space and time, and to use deep learning to predict those dynamics and test them experimentally.” 

Single-cell biology research has made it possible to build increasingly detailed maps of development. RNA velocity methods can help researchers estimate how cells move through developmental landscapes, while gene regulatory network approaches can identify relationships among genes. However, these methods have typically been used in parallel rather than together.  

“For a long time, cellular dynamics and gene regulation have largely been modeled separately,” said Fabian Theis, PhD, the study’s co-senior author and director of the institute of computational biology at Helmholtz Munich. “RegVelo brings those pieces together, allowing us to ask not only how cells are changing, but which regulatory interactions are helping drive those changes.”  

The framework jointly models splicing kinetics and gene regulatory relationships, allowing researchers to map the hidden timeline of cell development, predict how cells shift from one state to another, and test what might happen when specific regulators are perturbed. 

The framework can incorporate additional regulatory layers, including chromatin, protein activity, and other multimodal measurements. While the study’s limitations include simplifying assumptions around latent time, regulatory interactions, and computational cost, the results demonstrate a compelling proof of principle.

“When dynamic cell-state modeling is linked directly to gene regulation, it becomes possible to move closer to mechanism and then discovery,” Sauka-Spengler said. 

The post RegVelo AI Model Predicts Cell Fate, Tackles Developmental Disorders and Cancer appeared first on GEN – Genetic Engineering and Biotechnology News.

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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