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Synthetic Biology & Advanced Compound Production

eXoZymes’ Cell-Free Biomanufacturing Platform Gets Positive Feedback from Cayman Chemical

eXoZymes’ Cell-Free Biomanufacturing Platform Gets Positive Feedback from Cayman Chemical

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Officials at eXoZymes, which focuses on cell-free manufacturing and the development of AI-enhanced “exozymes,” say that an independent partner, Cayman Chemicals, ran eXoZymes’ technology at pilot scale and achieved results consistent with, and in some cases exceeding, earlier internal runs.

Cayman Chemical advanced the protocol from a 1-L setup to a 100-L pilot run, operating the reaction, downstream processing, and analysis independently. During the run, the team reported real-world conditions, including pH variation and precipitation, which often cause enzyme-based processes to fail.

Despite this, the reaction continued to perform reliably and delivered strong results, ultimately producing more than 500 g of pharma-grade N-trans-caffeoyltyramine (NCT) at 99.6% purity, according to an eXoZymes spokesperson, who added that a result like this is difficult to obtain in biomanufacturing without extensive purification steps.

“I’ve performed a lot of cell-based enzymatic biocatalysis over the years; it is a critical component of what we do at Cayman,” noted Patrick Westcott, director of catalog chemistry production at Cayman. “One common aspect of this work is a drop in efficacy during scale-up. Anytime you move up in scale orders of magnitude, a process changes enough that it is considered a different process altogether.

“During the experiment, from the first sample that we took, the analysis showed over a 99% conversion rate. There was some concern because I thought that maybe it was a little bit too high. So, we decided to take a second sample to see if it maintained a similar conversion rate. And we were a little surprised to find out that we actually did achieve this 99% conversion in our first 100-fold scale-up of their process. That was very much an aha moment for us!”

“This pilot run is an important validation of our cell-free platform, demonstrating that it performs reliably at scale and delivers strong results in the hands of an external partner. The fact that this project reached pilot scale in less than a year underscores our ability to move R&D at a disruptive pace, and just as importantly, it meaningfully reduces platform execution risk by showing that our technology can be transferred and operated successfully beyond our own labs,” stated Damien Perriman, CCO at eXoZymes.

“With more than 500 g of pharma-grade NCT now available from this run, we are actively engaging partners interested in evaluation, formulation development, and potential commercialization.”

The post eXoZymes’ Cell-Free Biomanufacturing Platform Gets Positive Feedback from Cayman Chemical appeared first on GEN – Genetic Engineering and Biotechnology News.

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Synthetic Biology & Advanced Compound Production

Electrorheoimaging Helps Manage Droplet Viscosity in Real-Time

Electrorheoimaging Helps Manage Droplet Viscosity in Real-Time

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A new technique combined with changes in material design is making reversible viscosity modulations possible, according to researchers from the University of Guelph in Ontario, Canada.

By connecting electrorheological properties to microscopic behaviors, biopharmaceutical manufacturers can simultaneously view real-time changes in emulsion microstructures and measure viscosity. Seeing droplet clustering, alignment, chaining, or breakup under electrorheological stress isn’t possible with traditional rheology. In practical terms, this still-experimental technique enables microfluidic droplets and droplet atomization, for example, to be controlled using electric fields.

Potential applications in biopharmaceutical manufacturing include mixing and blending, pumping and filtration, ultrafiltration, and filling. It may also improve injectable administration without harming stability.

Electrorheoimaging (ERI) builds on traditional rheology, which deals with the deformation and flow of liquids and other forms of matter. This new technique combines electrical forcing, rheological response, and imaging, co-authors Majid Bahraminasr, PhD, post-doctoral scholar, and Anand Yethiraj, PhD, professor, University of Guelph, explain in a recent paper.

In investigating the effects of direct currents on emulsions, Bahraminasr and Yethiraj found a “striking rheological response, previously unreported.” They noted “shear thinning and decreased intrinsic viscosity on one hand, and the emergence of field-induced bands in the spatial structure of the sheared emulsion, on the other.”

For alternating current, “Electrohydrodynamics is strongly frequency dependent,” they point out, adding that viscosity weakened as the electrical frequency increased.

When combined with a continuous phase that lowers electrohydrodynamic thresholds—an emulsion of castor oil dispersed in motor oil, in this research—the scientists were able to use an electric field to cause the emulsion to change viscosities instantly within a 30-fold range. Notably, viscosity could increase as well as decrease, and even “reduce viscosity below its quiescent, field-off state,” they report.

This suggests that this technique may be used to create a reversible viscosity switch that may be activated simply by tuning the frequency of the applied electrical field.

Unusual, but valuable

Although electrical field modulation is not a typical feature of biomanufacturing, it may help biopharmaceutical developers gain insights into energy dissipation, pattern formation, and nonequilibrium steady states in driven fluids.

For mAb manufacturing, therefore, applying ERI could help biopharmaceutical manufacturers:

  • Optimize processes for scale-up
  • Predict process behavior
  • Link bulk viscosity increases to specific microstructural events
  • Temporarily reduce viscosity during manufacturing
  • Restore stability post-processing
  • Inform excipient strategies

This work appears to be relevant to protein-based therapeutics, including mAbs, which often exhibit non-Newtonian rheology properties such as formation of submicrometer aggregates that complicate mixing, pumping, filtration, filling, and syringe usage, or that compromise product stability and ease of administration. “It also helps detect artifacts, such as bubbles, that could distort measurements,” the authors point out.

The post Electrorheoimaging Helps Manage Droplet Viscosity in Real-Time appeared first on GEN – Genetic Engineering and Biotechnology News.

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Synthetic Biology & Advanced Compound Production

HDX-MS Plus Computational Methods Provide Novel Approach to Study of Protein-Protein Interactions

HDX-MS Plus Computational Methods Provide Novel Approach to Study of Protein-Protein Interactions

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Researchers say they have used a high-sensitivity mass spectrometry technique to improve the accuracy of sandwich ELISA. The team, from biopharmaceutical company Regeneron, hopes their work will help researchers better understand protein-protein interactions during preclinical development of a drug.

“Essentially, we used a mass spectrometry-based method, along with a computational method and interferometry, to identify a protein-protein binding site, geometry, and binding ratio within a short period of time,” explains Yue Su, PhD, a scientist at Regeneron.

Sandwich ELISA is a common technique in the biopharmaceutical industry, Su explains. To quantify antigens in complex samples, an antigen is “sandwiched” between capture and detection antibodies. But, to pair properly, the antibodies need to target different binding sites on the antigen. If the binding is not specific enough, there can be competition for binding sites or unwanted binding, she says.

To check the pharmacokinetics of the company’s antibody drugs, she explains, they use sandwich ELISA, but the team that developed the specific ELISA wanted to make more informed decisions to optimize their assay design, as well as enhance its specificity and sensitivity.

To assist in better defining binding sites, Su’s team decided to use hydrogen-deuterium exchange mass spectrometry (HDX-MS), a powerful technique for studying protein-protein interaction and dynamics.

“If you imagine an antibody, an area that is bound and [an area that is] non-bound are protected differently. Therefore, [they are] exposed to the surrounding buffer environment differently, and we were able to identify the difference between these areas to investigate the antibody-antibody binding itself,” she explains.

The team combined HDX-MS with computational methods, such as AI, to understand the protein-protein interactions involved when using the sandwich ELISA, she says.

Now they hope that other researchers will adopt HDX-MS to help investigate sandwich ELISA and better understand protein-protein interactions more generally.

“To the best of our knowledge, this is the first time HDX-MS has been used to investigate the binding mechanisms in sandwich ELISA,” she says. “Hopefully, with new computational methods, such as AI, it can help facilitate our understanding of more protein-protein interactions.”

The post HDX-MS Plus Computational Methods Provide Novel Approach to Study of Protein-Protein Interactions appeared first on GEN – Genetic Engineering and Biotechnology News.

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Synthetic Biology & Advanced Compound Production

Benchtop Bioreactor Simplifies Macrophage Manufacturing

Benchtop Bioreactor Simplifies Macrophage Manufacturing

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A new laboratory protocol could make it far easier to generate one of the immune system’s most versatile cell types. Scientists led by Nico Lachmann, PhD, at Hannover Medical School have developed a standardized method to produce macrophages from induced pluripotent stem cells (iPSCs) using an intermediate-scale benchtop bioreactor.

Macrophages are central players in immunity, tissue repair, and disease progression, making them valuable tools in regenerative medicine, cancer research, and drug discovery. Yet producing these cells in a controlled, reproducible way—especially at volumes suitable for early-stage research—has remained a challenge. Many academic labs still rely on small, two-dimensional culture systems that are labor-intensive and prone to variability.

The new protocol addresses this gap by enabling macrophage production in suspension cultures within a compact bioreactor designed for volumes between 10 and 50 mL. The approach extends earlier large-scale manufacturing methods but adapts them for smaller, more accessible systems suited to academic research and preclinical studies.

The workflow unfolds over roughly 24 days and proceeds through two major milestones. First, iPSCs are coaxed into forming mesoderm-primed aggregates with hematopoietic potential—structures known as “hemanoids.” These aggregates then undergo hematopoietic differentiation, yielding mature macrophages that are ready for downstream applications without additional maturation steps.

Using this system, researchers can collect macrophages repeatedly over long-term cultures. Each vessel produces tens of millions of cells per harvest, and multiple collections can be obtained from a single culture. The bioreactor simultaneously monitors key environmental parameters—including temperature, pH, and carbon dioxide levels—and it improves reproducibility and cell quality compared with traditional open-culture methods.

Lachmann and his colleagues designed this system with usability in mind. The semi-automated platform requires minimal hands-on time and does not demand advanced bioprocessing expertise, making it accessible to laboratories with basic stem cell culture experience.

Beyond simplifying cell production, the method could expand experimental possibilities. iPSC-derived macrophages can be integrated into organoids, organ-on-chip systems, and disease models to better replicate human physiology in vitro. Such models are increasingly used to study inflammatory diseases, neurodegeneration, cardiovascular disorders, and cancer.

The standardized cell supply could also support emerging drug-safety assays and immunotherapy development. As researchers seek alternatives to animal testing and more human-relevant systems, scalable immune cell—manufacturing platforms may become an essential part of the experimental toolkit and commercial bioprocessing.

By bridging the gap between small-scale culture plates and industrial bioreactors, the new protocol provides a practical middle ground—one that could accelerate macrophage-based research across many fields and contribute to advances in biopharmaceutical manufacturing.

The post Benchtop Bioreactor Simplifies Macrophage Manufacturing appeared first on GEN – Genetic Engineering and Biotechnology News.

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