PrecisionLife and Ovation.io have signed a commercialization agreement to bring GLP-1 response genetic tests to the market. Today, the partners announced plans to launch both direct-to-consumer and laboratory developed tests later this year.
The companies had entered a collaboration at the end of last year, leveraging Ovation’s multi-omics and longitudinal clinical data and PrecisionLife’s advanced analytics platform to uncover genetic mechanisms of response to GLP-1 medication. Earlier this year, they reported the identification of a series of biomarker signatures that can quantitatively predict which patients are most likely to respond to GLP-1 therapies and sustain that response over time.
The partners are now actively working on translating this discovery into noninvasive genetic tests for patients to make informed decisions about the likely risks and benefits of these increasingly popular drugs, as well as for drug developers to stratify patients in clinical trials.
“Our teams have generated the world’s most detailed insights into why patients respond differently to these medicines,” said Steve Gardner, chief executive officer of PrecisionLife. “We will make these insights clinically actionable via noninvasive DNA tests supported by our results reporting platform and CLIA lab partners.”
PrecisionLife stressed that their findings go beyond the GLP-1 genetic predictors reported last week by 23andMe. “While that study highlighted a handful of variants associated with modest differences in outcomes, this work identifies combinatorial biomarker signatures that stratify patients and quantitatively predict response—and is already being translated into tests designed for use in real treatment decisions,” a company representative told Inside Precision Medicine.
Over the course of the next six months, PrecisionLife will reproduce, refine, and validate their findings using additional datasets provided by Ovation, including studies to confirm the predicted response to GLP-1 drugs including semaglutide and tirzepatide in a real-world context.
The launch of a consumer DNA test is expected to enable patients to understand their individual safety, efficacy, and tolerability profile for GLP-1 drugs before starting treatment. This could also offer providers a clearer basis for selecting therapies and help payors make more sustainable coverage decisions. The collaborators have stated they will evaluate the opportunity of using these tests to inform reimbursement decisions and expand coverage of certain health plans based on an individual’s predicted response.
For drug developers, laboratory developed tests (LDT) could open up opportunities for more precise patient stratification, improving the probability of success in clinical trials evaluating the expansion of GLP-1 drugs into new indications. The companies are currently in discussions with various stakeholders and sponsors to deploy the LDTs as stratification tools in a clinical setting.
“We’re confident that together we can translate those insights into commercial outcomes and products in GLP-1s and other diseases with huge clinical impact,” said Curt Medeiros, chief executive officer of Ovation.io.
Going forward, the partners will continue to validate their findings and expand the scope of the studies, including identifying additional markers of safety and tolerability to GLP-1 drugs as well as pinpointing further efficacy and safety signals for individual molecules.
The Centers for Medicare and Medicaid Services is proposing to repeal a pathway that currently allows breakthrough devices to qualify for supplementary payments without proving they provide a substantial clinical improvement over alternatives.
Access to lifesaving new technologies can be stymied when hospitals don’t get paid enough to cover their costs. So since 2001, Medicare has given innovative devices a chance at extra payments when they meet three criteria: they’re new and different from what’s currently available, they offer a clinical improvement over existing options, and they’re especially costly.
Since 2021, devices that receive breakthrough designation from the Food and Drug and Administration have gotten an even sweeter deal: In order to qualify for the extra payments, they only have to demonstrate they’re expensive.
For many patients, especially those with chronic or life-threatening diseases, treatment is not a single intervention but a relentless routine.
Cancer patients can spend years tethered to infusion schedules, returning weekly for IV therapies that dictate where they can live, travel, and work. Children with rare metabolic disorders may rely on frequent enzyme infusions, with entire rooms of supplies needed to sustain their care. And for patients in low-resource settings, life-saving biologic drugs often remain out of reach altogether due to cost and infrastructure.
These realities highlight a critical challenge in modern medicine: some of the most potent therapies are the most difficult to deliver, necessitating repeated dosing at centralized locations.
Duracyte, a newly launched biotechnology company, is pioneering a potentially transformative approach to medicine by developing a “living pharmacy” inside the human body. Its core technology, the Hybrid Advanced Molecular Manufacturing Regulator (HAMMR), is an implantable bioreactor designed to produce biologic drugs directly within patients. This innovation could fundamentally change how medicines are manufactured, delivered, and even conceived.
A prototype of Hybrid Advanced Molecular Manufacturing Regulator (HAMMR), a rechargeable implantable device capable of sensing biological signals, monitoring tumor environments and dynamically adjusting therapeutic output in real time. [Rice University]
The founding team combines expertise across bioengineering, medicine, and biotech. Omid Veiseh, PhD, is a Rice University professor and RBL LLC managing partner focused on implantable cell therapies, while Paul Wotton, PhD, is a veteran biotech CEO with deep commercialization experience. Jonathan Rivnay, PhD, of Northwestern specializes in bioelectronics; Robert Langer, ScD, and Daniel Anderson, PhD, are MIT leaders in drug delivery and gene therapy; and Siddharth Krishnan, PhD, of Stanford, contributes expertise in wireless power and implantable devices.
Duracyte is the third venture created by RBL LLC, a Houston-based biotech studio founded by Rice University in 2024. Operating from Helix Park, RBL focuses on rapidly translating breakthrough research into real-world therapies, particularly in areas like oncology and autoimmune disease. Duracyte’s progress is further supported by ARPA-H’s THOR project, a nationwide collaboration aimed at advancing implantable biohybrid therapies from research to clinical application.
Honey, I shrunk the bioreactor
Biologic drugs, including antibodies, hormones, and enzymes, have become a cornerstone of modern medicine. They now represent a substantial share of the pharmaceutical market, treating conditions ranging from cancer to autoimmune diseases. But their production and delivery remain cumbersome.
Traditionally, biologics are manufactured in large-scale industrial bioreactors, purified, stabilized, and shipped to clinics, where they are administered via injection or intravenous infusion. This process is expensive, logistically demanding, and often burdensome for patients, who may require frequent hospital visits over months or years.
Veiseh, a professor of bioengineering at Rice University, has spent much of his career questioning whether this paradigm could be fundamentally reimagined. “What if we could bring this biomanufacturing to the patients and develop implantable bioreactors or injectable bioreactors whereby the biologic could be produced in the body?” Veiseh told Inside Precision Medicine. That question now underpins HAMMR.
At its core, HAMMR is a miniaturized, implantable bioreactor. Roughly the size of a small medical implant, the device houses genetically engineered human cells capable of producing therapeutic proteins. Unlike traditional drug delivery systems, which release pre-manufactured compounds, HAMMR generates biologics inside the patient’s body.
To accomplish this, the device replicates key functions of industrial bioreactors, but in a compact, implantable form. It supplies nutrients and oxygen to the cells, supports their viability, and allows for controlled production of therapeutic molecules.
One of the key technological innovations lies in how HAMMR generates oxygen. Using electrolysis—a well-established chemical engineering process—the device splits water molecules into hydrogen and oxygen. This hybrid oxygenation bioelectronics system for implanted therapy (HOBIT) component provides a steady, localized oxygen supply to sustain the embedded cells. “We’ve got a way to do electrolysis with low power and in a safe manner that actually allows this to be viable for the engineered cells,” Veiseh explained.
Real-time, feedback-controlled medicine
The device also incorporates electronic controls and sensors. Electrical signals can activate or deactivate the cells, effectively turning drug production on or off. Meanwhile, onboard sensors monitor pharmacokinetic and pharmacodynamic data.
This data is transmitted wirelessly to an external interface, enabling clinicians to adjust dosing in real time. Veiseh said, “The implanted device also communicates with an app that allows us to control dosing and get a lot of data from the patient as far as their physiological conditions, meaning the impact the drug is having on the body.”
One of the most transformative aspects of HAMMR is its potential to enable feedback-controlled drug delivery. Rather than administering fixed doses on a set schedule, clinicians could tailor therapy dynamically based on continuous biological data. “For the first time ever, we can create feedback drug delivery systems where you can dose to a pKa level or, better yet, to a pharmacodynamic level, which allows for that precise dosing for every patient,” said Veiseh.
This capability could be especially impactful in oncology, where patients often receive complex combinations of biologics. Current regimens may involve multiple drugs administered on different schedules, requiring frequent clinic visits and careful coordination.
Veiseh described a typical scenario: patients receiving checkpoint inhibitors such as ipilimumab and nivolumab, along with additional biologics like bevacizumab. These therapies often require weekly infusions over extended periods. “The vast majority of patients are getting IV infusions weekly and they are living longer, which is great,” he said. “But now you have patients that are on this regimen for three years.”
HAMMR aims to replace this model with a single implanted device capable of producing multiple drugs, with dosing adjusted digitally rather than through repeated clinical visits. “We’re moving away from physical prescriptions to a world of digital prescriptions,” Veiseh said.
The convergence of components
The idea of implantable bioreactors has been explored for years, but only recently have the necessary technologies matured enough to make it feasible. According to Veiseh, advances in several fields have converged: electronic miniaturization, wireless power transfer, synthetic biology, and biomaterials engineering. Together, these innovations enable the integration of complex functionalities into a small, biocompatible device.
By leveraging established technologies and adapting them for medical use, the team aims to reduce development risk and accelerate regulatory approval.
Wotton, a seasoned biotech executive working with the team, emphasized that many of the underlying components are not entirely new; they are adapted from existing technologies. “One of the advantages here is that these guys have been really intelligent when they’ve taken off-the-shelf technologies,” Wotton told Inside Precision Medicine. “The oxygen technology is lifted from what’s already used in submarines… The battery charging work is being done… The RPE cell lines that we work with… have successfully gotten into the clinic.”
Looking ahead, the team envisions integrating artificial intelligence into the platform. With continuous data collection from implanted devices, machine learning algorithms could identify patterns in treatment response and optimize therapy over time. “You can imagine… this device could now cycle through different therapies, and as it starts seeing efficacy responses, it starts learning,” Veiseh said.
Such a system could enable highly personalized medicine, adapting treatment strategies based on real-time data and accumulated experience across patients.
The HAMMR platform is built around the preparation of polymer-encapsulated cells, obtained from the human immortalized retinal pigment epithelia (RPE) cell line ARPE-19, which has already been used to generate cytokines for treating intraperitoneal tumors with oversight from the U.S. Food and Drug Administration (FDA). This provides a regulatory advantage, as the cells have an established safety profile. These preparations of ARPE-19 cells can be engineered to produce a wide range of biologics beyond cytokines.
A cost-cutting catalog
Veiseh noted that there are more than 300 FDA-approved biologics in the United States, and his team has already created versions of over 150 within this system. “This platform has the potential to really disrupt the biotech market as it exists today,” he said.
The implications extend beyond oncology. Wotton highlighted potential applications in autoimmune diseases, infectious diseases, and metabolic disorders. “There are so many applications of this technology,” he said. “Whether it’s in oncology… or… delivering antibodies like Humira to treat chronic diseases… there are applications where you can treat type two diabetes… HIV.” In each case, the goal is the same: replace repeated injections or infusions with a long-lasting implant that continuously produces therapeutic proteins.
HAMMR could have significant implications for the cost and accessibility of biologic therapies. Biologics are among the most expensive treatments in medicine, with some costing hundreds of thousands of dollars per year. Much of this cost stems from manufacturing, purification, and distribution. By producing drugs directly inside the body, HAMMR could dramatically reduce these costs. “The cost of goods is actually quite low relative to manufacturing today,” Veiseh said. “This is like one-tenth of the price.”
Wotton echoed this point, suggesting that the platform could replace expensive annual treatment regimens with lower-cost implantable devices. “Imagine what you could do if you could replace the $250,000 a year injectable schedule,” Wotton said.
This cost reduction could be particularly impactful in low-resource settings. Veiseh noted that the Gates Foundation has supported the project in part because of its potential to expand access to biologics in developing countries. “Biologics are way too expensive for sub-Saharan Africa,” he said. “But a device that can produce HIV treatments… once yearly… now it becomes… practical for that world too.”
Houston, we have clinical liftoff
Backed by more than a decade of research funding exceeding $100 million from agencies and organizations including DARPA, ARPA-H, the NIH, and the Gates Foundation, Duracyte is preparing to bring its first device into clinical trials. Duracyte plans to initiate a Phase I clinical trial this year evaluating patients with recurrent ovarian cancer. The company has already held multiple meetings with the FDA and completed a pre-IND (Investigational New Drug) meeting. “We have a clear plan as to what it takes to file an IND,” Veiseh said. “We’re on track to actually file… before the end of this year.”
If all goes as planned, the first patients could receive the implant by late this year or early next year. The trial will be conducted in Houston, leveraging partnerships with leading medical institutions, including the renowned MD Anderson Cancer Center. “Our partners at MD Anderson… will be running the first clinical trial,” Wotton said. “Taking advantage of the ecosystem down in Houston.” The proximity of Veiseh’s lab to the clinical site has helped accelerate development, enabling close collaboration between researchers and clinicians.
Despite its promise, the HAMMR platform faces significant challenges. Integrating multiple complex technologies into a single device is inherently difficult, and clinical validation will be critical. Execution risk remains high, particularly in selecting initial indications and navigating regulatory pathways. “We can’t do everything all at once,” Veiseh said. “It’s really thinking about what the value creation is at early stages.”
Prioritization will be key, given the platform’s broad potential. With hundreds of possible biologics and numerous disease targets, choosing the right starting point could determine the company’s trajectory. Wotton emphasized this challenge as well. “What are the challenges we have? Making the right choices with respect to where we go next,” Wotton said.
If successful, HAMMR could mark a fundamental shift in how medicines are delivered and even defined. Instead of prescribing drugs as physical products, physicians could prescribe programmable devices that manufacture therapies on demand. In this model, the distinction between drug and device blurs, giving rise to a new category of therapeutics. “This is so different than what pharma does,” Veiseh said. “I think it’s really interesting to see whether they are also eager to imagine a future of medicine, which gets away from the injectables.”
For now, that future remains speculative. But with clinical trials imminent and a strong foundation of research behind it, Duracyte’s “living pharmacy” is poised to test whether the idea can move from concept to clinical reality.
As Wotton put it, “This is just the tip of the iceberg.”
A randomized Phase II trial offers a rare signal of progress in pancreatic cancer, a disease long marked by therapeutic stagnation, with investigators reporting that the experimental agent elraglusib (9-ING-41) improved survival when added to standard chemotherapy of gemcitabine plus nab-paclitaxel (GnP).
Published in Nature Medicine, the study evaluated the novel drug—developed within an academic setting at Northwestern University—in patients with metastatic pancreatic cancer. The findings suggest that targeting glycogen synthase kinase-3 beta (GSK-3β), a protein not previously exploited clinically in this disease, could open a new therapeutic avenue.
“This is one of the first trials in a randomized setting that has been positive in pancreatic cancer in the last decade,” said Devalingam Mahalingam, MD, PhD, a study leader at Northwestern University. “There was really a barren spell… many failed trials. So it’s nice to see a positive trial.”
A modest but meaningful survival gain
The multicenter trial enrolled 233 patients across North America and Europe, randomly assigning them to receive chemotherapy alone or in combination with elraglusib. Patients receiving the combination lived a median of 10.1 months compared with 7.2 months for chemotherapy alone, and the addition of elraglusib reduced the risk of death by 38%.
Perhaps more striking, survival at one year doubled in the experimental arm (44% vs. 22%), and approximately 13% of patients remained alive at two years—an uncommon outcome in metastatic pancreatic cancer.
Mahalingam emphasized that the benefit was not necessarily reflected in higher tumor response rates. Instead, patients appeared to derive prolonged disease control.
“We didn’t really see much more tumor shrinkage compared to chemo alone,” he said. “But patients stayed on the treatment arm longer… sometimes they would reduce or drop the chemo and just stay on the drug.”
This pattern, he added, points toward a mechanism beyond direct cytotoxicity.
A different mechanism of action
Unlike conventional chemotherapy, which primarily targets rapidly dividing cells, elraglusib appears to act on the tumor microenvironment—the complex ecosystem of immune cells, stromal tissue, and signaling molecules surrounding cancer cells.
The drug inhibits GSK-3β, a protein involved in multiple cellular processes, including metabolism, signaling pathways, and immune regulation. While broadly expressed in normal tissues, GSK-3β can be co-opted by tumors to promote growth and suppress immune responses.
“GSK-3 beta is expressed in many tumors,” Mahalingam said. “It’s part of a central regulator of normal cell functioning… but in cancer, this pathway is used to allow for tumor growth and proliferation.”
Preliminary analyses from the trial suggest that elraglusib may enhance antitumor immunity. Biopsies and blood-based markers indicated changes consistent with immune activation, supporting the hypothesis that the drug helps re-engage the immune system in a tumor type typically resistant to immunotherapy.
“We saw what we call immunomodulatory effects,” Mahalingam noted. “The immune cells might be driving some of the survival benefit we see.”
This is particularly notable given the long-standing failure of checkpoint inhibitors in pancreatic cancer, a tumor characterized by a highly immunosuppressive microenvironment.
Developed in academia
Elraglusib’s development trajectory also sets it apart. The compound originated in academic laboratories more than a decade ago, with early work spanning Northwestern University, the University of Illinois Chicago, and the Mayo Clinic.
“This is what not many drugs are—developed within an academic setting,” Mahalingam said. “It was founded in a chemistry lab… and then moved into a spin-off company to raise funding for trials.”
After preclinical development between 2010 and 2015, the drug entered early-phase trials around 2017 and has since been evaluated across multiple tumor types, with a recent focus on pancreatic cancer.
The randomized Phase II trial marks the first time a GSK-3β inhibitor has demonstrated efficacy beyond early-stage testing.
Broad eligibility, real-world relevance
Investigators designed the study with relatively broad inclusion criteria, enrolling patients with high tumor burden and poor nutritional status—characteristics common in real-world pancreatic cancer populations but often excluded from clinical trials.
“We allowed patients with very large volumes of disease,” Mahalingam said. “We did not restrict patients for albumin… we didn’t engineer the study to look better.”
This approach may partly explain the modest median survival difference, as some patients progressed too quickly to benefit. However, it also strengthens the generalizability of the findings.
Safety and next steps
Side effects associated with elraglusib were generally manageable and consistent with chemotherapy, including hematologic toxicities, fatigue, and reversible vision changes.
The next step will be a confirmatory Phase III trial, with discussions ongoing with regulators.
“We really need to confirm the studies in a large phase three trial,” Mahalingam said, adding that trial design considerations include how to integrate emerging therapies such as KRAS inhibitors.
Investigators are also exploring combination strategies, including pairing elraglusib with immunotherapy or alternative chemotherapy regimens. Early safety studies suggest such combinations are feasible, though efficacy data remain limited.
Potential beyond pancreatic cancer
Given the central role of GSK-3β in multiple cellular pathways, researchers are already investigating the drug’s potential in other malignancies, including hematologic cancers and pediatric tumors such as Ewing sarcoma and medulloblastoma.
“This is a new class of potential cancer therapeutics,” Mahalingam said. “Certainly, there would be excitement in seeing where this target can be applied to other tumors.”
While challenges remain, the trial’s results offer cautious optimism in a field where progress has been incremental at best.
“Even if it means that this class of drugs can be used for future drug development,” Mahalingam said, “it gives an opportunity to expand therapeutic potential—not just for pancreatic cancer, but beyond.”
Background: The integration of artificial intelligence (AI) into clinical practice is contingent on public trust. This trust often depends on physician oversight, yet a significant gap exists between the need for AI-competent physicians and the current state of medical education. While the perspectives of students and experts on this gap are known, the views of the US general public remain largely unquantified. Objective: This study aimed to assess US public perceptions regarding AI in medicine and the corresponding emergent needs for medical education. We specifically sought to quantify public trust in different diagnostic scenarios, concerns about physician overreliance on AI, support for mandatory AI education, and priorities for the future focus of medical training. Methods: We conducted a cross-sectional, web-based survey of adults in the United States in November 2025. Participants (N=524) were recruited via SurveyMonkey Audience. We calculated descriptive statistics, frequencies, proportions (percentages), and 95% CIs for all main survey items. Results: A total of 524 participants completed the survey. Most (n=329, 62.8%; 95% CI 58.6%‐66.9%) placed the most trust in a physician’s diagnosis based on their expertise alone; only 7.8% (n=41; 95% CI 5.5%‐10.1%) trusted an AI-first diagnostic model. Trust was highly contingent on training: 93.9% (n=492) of participants rated formal physician training on AI limitations as “essential” or “very important.” Widespread concern about physician overreliance on AI was reported, with 81.1% (n=425) being “very concerned” or “extremely concerned.” Consequently, 85.1% (n=446) agreed or strongly agreed that training on AI use, ethics, and limitations should be mandatory in medical school. When asked about future educational priorities, 70.2% (n=368; 95% CI 66.3%‐74.1%) believed that medical education should focus on human-centered skills (eg, empathy and communication) over clinical skills. Conclusions: The US public expressed conditional trust in medical AI, strongly preferring physician-led and critically supervised models. These findings reveal a clear public mandate for medical education reform. The public expects future physicians to be mandatorily trained to appraise AI, understand its limitations, and refocus their professional development on the human-centered skills that technology cannot replace.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/3874abd2d5f25c78f21987a16f3af6be" />
Alterations in excitation/inhibition (E/I) balance and changes in motor neurons (MN) activity may contribute to MN vulnerability in ALS. The balance of pathogenic versus adaptive changes occurring in inhibitory synapses and affecting E/I balance remain unclear. Confocal microscopy of MN from P45 male SOD1G93A mice reveal downregulated GlyR but upregulated GABAR clusters at inhibitory synapses. GlyR and GABAR respond to PSAM and DREADD chemogenetic alterations of MN excitability, with increased activity driving increase in inhibitory clusters. An E3 ligase-conjugated intrabody (GFE3) degrades Gephyrin, decreases GABAR and GlyR clusters, increases net activity, and downregulates disease markers. However, simultaneous decrease of inhibition and increased activity by actPSAM and GFE3 shows no net beneficial effects on disease markers. Thus inhibitory synapses are involved in the early phases of ALS pathogenesis and respond to persistent homeostatic loops, and their suppression delivers a net activity increase, offering potential benefits on disease pathways.
Research led by Wageningen University in the Netherlands and the Van Andel Institute (VAI) in Michigan has shown that ThermoCas9, a variant of CRISPR, can distinguish tumor DNA from healthy DNA and selectively cut only the former, marking a potential step toward a highly precise cancer therapy.
The method relies on DNA methylation, a process in which methyl groups are added to DNA to regulate whether genes are on or off. In cancer cells, DNA methylation is altered and can therefore act as a molecular “fingerprint” that differentiates tumor cells from healthy ones.
“ThermoCas9 is the first CRISPR-associated enzyme to respond to differences in the most abundant type of DNA methylation in human and other eukaryotic cells,” explained co-senior author John van der Oost, PhD, from Wageningen University. “This means we now have a system that we can target specifically toward tumor cells.”
The study, published in Nature, represents the first time a CRISPR-based method has relied on methylation to target human cancer cells.
“ThermoCas9 uses methylation like an address to precisely target cancer cells while leaving healthy cells untouched,” added co-senior author Hong Li, PhD, from VAI. “The findings could be a game changer.”
After analyzing ThermoCas9’s structure and finding that it can distinguish between unmethylated and methylated genes, Li and team introduced the enzyme into different types of healthy human cells with distinct methylation landscapes and into breast and colorectal cancer cells.
They found that ThermoCas9 cut DNA in the tumor cells while leaving healthy DNA intact, suggesting that the system can detect subtle chemical differences between healthy and tumor cells and act on them.
“ThermoCas9 is a perfect example of the value of fundamental research; you have to know how these individual pieces work together,” said Li. “We used biochemistry and structural biology to discover a mechanism that we one day hope will lead to more precise, effective cancer treatment.”
Although the study highlights the potential of ThermoCas9 as a cancer treatment, it does not show that the selective DNA damage it inflicts leads to tumor cell death. The researchers next steps will focus on damaging tumor DNA sufficiently to trigger cell death.
Of note, aberrant methylation patterns also play a role in diseases other than cancer, including autoimmune disorders. It is therefore possible that ThermoCas9 or a similar CRISPR tool could evolve into a versatile molecular strategy that recognizes diseased cells by their chemical “signature” and selectively disables them.
Researchers have found an epigenetic switch that pancreatic cancer cells use to protect themselves against genomic instability. In a study published in Cancer Research, the team reports that blocking the epigenetic regulator DPY30 triggered immune cell infiltration into pancreatic tumors in mice, sensitizing them to immunotherapy.
Frequently diagnosed at advanced stages, pancreatic cancer is often resistant to conventional therapies and shows limited response to immunotherapy. This leaves patients with few effective treatment options.
“As cancer biologists, we are intrigued by the remarkable ability of pancreatic cancer cells to tolerate genomic instability and sustained replication stress while continuing to proliferate and evade immune surveillance,” said Francesca Citron, PharmD, PhD, instructor of genomic medicine at The University of Texas MD Anderson Cancer Center and lead author of the study. “This paradox led us to investigate the adaptive mechanisms that enable cancer cells to buffer genomic instability, particularly by protecting replication forks and preventing catastrophic DNA damage.”
The researchers were interested in finding out whether epigenetic regulators may play a direct role in safeguarding the integrity of replication forks, where DNA is copied as cells divide. Under stress, DNA replication is typically disrupted, for instance as cancer cells continue dividing and accumulating mutations that result in genomic instability. However, Citron’s team discovered that pancreatic cancer cells rely on DPY30 to protect DNA replication forks under stress and continue multiplying in spite of genomic instability.
DPY30 belongs to a group of proteins that together form the WRAD/COMPASS complex, which is involved in epigenetics regulation. The study found that this component was able to switch the entire complex from playing a global epigenetics function to a localized role at stressed replication forks, where DPY30 stabilized.
“Historically, WRAD core components, particularly DPY30, have been primarily studied in the context of histone methylation and transcriptional regulation,” said Citron. “Our findings significantly expand this paradigm by demonstrating that these factors play a direct role in maintaining replication fork stability under conditions of stress. Importantly, we also establish a link between this mechanism and modulation of the tumor immune microenvironment, providing a conceptual bridge between replication stress and immune response.”
In a mouse model of pancreatic cancer, DPY30 inhibition destabilized replication forks, leading to increased genomic instability and activating inflammatory signaling pathways. This then triggered the recruitment of tumor-infiltrating lymphocytes and turned previously immunologically “cold” tumors into “hot” tumors that responded to immunotherapy.
“Inhibiting DPY30 leads to increased replication-associated DNA damage, which in turn robustly enhances immune signaling pathways,” said Citron. “This dual effect, on genome stability and immune activation, opens new therapeutic opportunities to impair replication fork protection while simultaneously stimulating anti-tumor immune responses.”
Furthermore, biopsies from pancreatic cancer patients showed that higher levels of DPY30 expression were associated with higher tumor grades, a poorer prognosis and lower response rates to immunotherapy. Together, these findings point at DPY30 as both a therapeutic target and a biomarker to stratify patients who are most likely to benefit from immunotherapy.
Going forward, the researchers plan to dive deeper into how HPY30 influences immune cell recruitment and activation within the tumor microenvironment. In parallel, they will be exploring pharmacological strategies to inhibit DPY30 and testing their efficacy in preclinical studies. Citron added: “Ultimately, our goal is to develop rational combination therapies that drive more effective and durable responses in patients.”
A consortium of companies has developed what they call a digital twin of a microbial process to produce protein A.
Novasign, based in Vienna, hopes its participation through the ECOnti consortium will help manufacturers slash the costs of microbial proteins by improving experimental design.
According to the company, the digital twin can reduce the number of experiments needed to understand process behavior by 70% compared to Design of Experiments (DoE).
“Generally, the biggest problem in the industry right now is it’s not very efficient,” explains Mark Duerkop, PhD, CEO of Novasign.
“We need methods to learn more efficiently from experiments, design better experiments, and adapt process trajectories if something goes wrong.”
According to Duerkop, Novasign began developing an end-to-end digital twin of the full processing chain for microbial protein production as part of the ECOnti consortium three years ago.
Novasign says it develops digital twins spanning an entire process—from upstream to downstream—with the goal of improving both process development and manufacturing efficiency.
“The digital twin supports process development by systematically recommending the next set of experiments based on model-informed insights,” he says.
Setup of the Novasign ECOnti Digital Twin Technology
“During manufacturing, it can detect deviations from the intended process trajectory and support corrective actions.”
For example, if the digital twin is used to recover a process following disturbances, such as pH shifts or feed pump failure, manufacturers could significantly reduce product losses.
However, this remains for the future, he says, as the U.S. Food and Drug Administration (FDA) requires extensive validation before approving self-optimizing or autonomous manufacturing processes.
At the recent Bioprocessing Summit Europe, Duerkop presented a showcase on using the Novasign Studio software for full process control for 30 consecutive days.
He also showed how the software can use small-scale experimental data to inform scale-up and, in biosimilar development and viral vector manufacturing, can reduce experimental effort by up to 64%.
In the push to de-risk biologics manufacturing, downstream purification steps are increasingly under the microscope. Now, new research led by Jonathan Bones, PhD, principal investigator in the characterization and comparability group at the National Institute for Bioprocessing Research in Dublin, and his colleagues provided compelling evidence that ultrafiltration and diafiltration (UF/DF) deliver robust clearance of process-related leachables—while also offering a predictive framework to better understand that performance.
Although UF/DF has long been assumed to reduce small-molecule contaminants, systematic data have been scarce. To address this gap, the team evaluated 28 representative organic compounds spiked into three distinct protein systems. Using liquid chromatography–high resolution mass spectrometry, they tracked how effectively these compounds were removed during UF/DF operations.
The results were striking. Twenty-four of the compounds demonstrated greater than 98% clearance across all three protein processes. Notably, variations in protein characteristics and process parameters had minimal impact on removal efficiency. Instead, clearance behavior was remarkably consistent, as reflected in similar sieving coefficients across the systems.
The intrinsic physicochemical properties of the leachables impacted clearance. Among these, lipophilicity—expressed as the octanol-water partition coefficient (Log P)—emerged as the dominant factor. Compounds with Log P values below four exhibited near-ideal clearance, while even highly hydrophobic molecules (Log P above seven) still achieved removal rates exceeding 93%. Molecular weight, polarizability, and solvent-accessible surface area also contributed to clearance outcomes.
Beyond empirical findings, the study advances the field with predictive modeling. By applying orthogonal partial least squares (OPLS) regression, the researchers developed tools capable of estimating sieving coefficients based on compound properties. These models could prove invaluable for anticipating leachable behavior without exhaustive experimental testing.
The implications are significant. As regulatory scrutiny around extractables and leachables intensifies, demonstrating effective clearance becomes central to product safety. This work not only confirms that UF/DF is a powerful mitigation step but also equips developers with quantitative tools to support risk assessments.
In an industry where unseen contaminants can pose outsized risks, the ability to both measure and predict their removal marks a meaningful step forward.
