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Experimental vaccine for common cancer shows potential in clinical trial

A vaccine for pancreatic cancer could serve as a promising new therapy.

At Memorial Sloan Kettering Cancer Center (MSK) in New York, an experimental approach to treating the cancer with a messenger RNA (mRNA)-based therapeutic vaccine “continues to show potential” in reducing the risk of the disease returning after surgery, according to a press release.

Results from the phase 1 clinical trial, published in the journal Nature, revealed that the vaccine triggered an immune response in a small patient group.

This immune-cell activation persisted for nearly four years after treatment, the release stated.

Patients who received the vaccine and showed an immune system response were more likely to remain cancer-free by their three-year follow-up.

Vinod Balachandran, MD, principal investigator of the trial and senior study author at MSK, stated his optimism about the efficacy of this treatment.

“We find that with RNA vaccine technology, we can teach the immune system to recognize pancreatic cancer, and this immune response could potentially last for many years,” he said.

“The ability to trigger a robust, long-lasting immune response is a requisite feature for any cancer vaccine.”

As pancreatic cancer is “difficult to treat,” Balachandran shared his surprise that the immune system responded in some patients.

“We are encouraged to see that our approach can teach the immune system to recognize pancreatic cancer, that the immune response is potent and that it may potentially impact patients,” he said.

“The ability to trigger a robust, long-lasting immune response is a requisite feature for any cancer vaccine.”

“Although the findings are promising, these vaccines are still in the early stages of testing,” Balachandran said.

The team is planning a larger study “to further test these therapeutic cancer vaccines in patients with surgically removable pancreatic cancer.”

Of the 16 participants, the vaccine stimulated an immune response in half of them. The cancer vaccine was personalized for each participant to target specific proteins found in their form of the disease.

The patients also received an immunotherapy drug (atezolizumab) and standard-of-care chemotherapy after receiving surgery.

Therapeutic cancer vaccines like this one, referred to as autogene cevumeran, are meant to treat the cancer instead of preventing it, by training the immune system to “recognize cancer cells as foreign,” according to the researchers.

The vaccine is meant to target early stages of cancer that have not spread, where tumors can be surgically removed, to “help delay or prevent recurrence.”

Balachandran noted that this approach could potentially be applied to other forms of cancer as well.

“If you can do this in pancreatic cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types.”

“For patients with pancreatic cancer, our latest results continue to support the approach of using personalized mRNA vaccines to target neoantigens in each patient’s tumor,” he said.

“If you can do this in pancreatic cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types.”

Pancreatic cancer remains one of the deadliest cancers, as only about 13% of patients are alive five years following diagnosis, according to MSK and the American Cancer Society.

Common therapies like chemotherapy, radiation and immunotherapies are “largely ineffective” against pancreatic cancer, MSK stated, which makes new therapies “urgently needed.”

News Team by — February 21, 2025 By News Team in Trending Now
AI system predicts protein fragments that can bind to or inhibit a target

All biological function is dependent on how different proteins interact with each other. Protein-protein interactions facilitate everything from transcribing DNA and controlling cell division to higher-level functions in complex organisms.

Much remains unclear, however, about how these functions are orchestrated on the molecular level, and how proteins interact with each other—either with other proteins or with copies of themselves.

Recent findings have revealed that small protein fragments have a lot of functional potential. Even though they are incomplete pieces, short stretches of amino acids can still bind to interfaces of a target protein, recapitulating native interactions. Through this process, they can alter that protein’s function or disrupt its interactions with other proteins.

Protein fragments could therefore empower both basic research on protein interactions and cellular processes, and could potentially have therapeutic applications.

Recently published in Proceedings of the National Academy of Sciences, a new method developed in the Massachusetts Institute of Technology Department of Biology builds on existing artificial intelligence models to computationally predict protein fragments that can bind to and inhibit full-length proteins in E. coli. Theoretically, this tool could lead to genetically encodable inhibitors against any protein.

The work was done in the lab of associate professor of biology and Howard Hughes Medical Institute investigator Gene-Wei Li in collaboration with the lab of Jay A. Stein (1968) Professor of Biology, professor of biological engineering, and department head Amy Keating.

Leveraging machine learning

The program, called FragFold, leverages AlphaFold, an AI model that has led to phenomenal advancements in biology in recent years due to its ability to predict protein folding and protein interactions.

The goal of the project was to predict fragment inhibitors, which is a novel application of AlphaFold. The researchers on this project confirmed experimentally that more than half of FragFold’s predictions for binding or inhibition were accurate, even when researchers had no previous structural data on the mechanisms of those interactions.

“Our results suggest that this is a generalizable approach to find binding modes that are likely to inhibit protein function, including for novel protein targets, and you can use these predictions as a starting point for further experiments,” says co-first and corresponding author Andrew Savinov, a postdoc in the Li Lab. “We can really apply this to proteins without known functions, without known interactions, without even known structures, and we can put some credence in these models we’re developing.”

One example is FtsZ, a protein that is key for cell division. It is well-studied but contains a region that is intrinsically disordered, and therefore, especially challenging to study. Disordered proteins are dynamic, and their functional interactions are very likely fleeting—occurring so briefly that current structural biology tools can’t capture a single structure or interaction.

The researchers leveraged FragFold to explore the activity of fragments of FtsZ, including fragments of the intrinsically disordered region, to identify several new binding interactions with various proteins. This leap in understanding confirms and expands upon previous experiments measuring FtsZ’s biological activity.

This progress is significant in part because it was made without solving the disordered region’s structure, and because it exhibits the potential power of FragFold.

“This is one example of how AlphaFold is fundamentally changing how we can study molecular and cell biology,” Keating says. “Creative applications of AI methods, such as our work on FragFold, open up unexpected capabilities and new research directions.”

Inhibition, and beyond

The researchers accomplished these predictions by computationally fragmenting each protein and then modeling how those fragments would bind to interaction partners they thought were relevant.

They compared the maps of predicted binding across the entire sequence to the effects of those same fragments in living cells, determined using high-throughput experimental measurements in which millions of cells each produce one type of protein fragment.

AlphaFold uses co-evolutionary information to predict folding, and typically evaluates the evolutionary history of proteins using something called multiple sequence alignments (MSAs) for every single prediction run. The MSAs are critical, but are a bottleneck for large-scale predictions—they can take a prohibitive amount of time and computational power.

For FragFold, the researchers instead pre-calculated the MSA for a full-length protein once, and used that result to guide the predictions for each fragment of that full-length protein.

Savinov, together with Keating Lab alumnus Sebastian Swanson, Ph.D., predicted inhibitory fragments of a diverse set of proteins in addition to FtsZ. Among the interactions they explored was a complex between lipopolysaccharide transport proteins LptF and LptG. A protein fragment of LptG inhibited this interaction, presumably disrupting the delivery of lipopolysaccharide, which is a crucial component of the E. coli outer cell membrane essential for cellular fitness.

“The big surprise was that we can predict binding with such high accuracy and, in fact, often predict binding that corresponds to inhibition,” Savinov says. “For every protein we’ve looked at, we’ve been able to find inhibitors.”

The researchers initially focused on protein fragments as inhibitors because whether a fragment could block an essential function in cells is a relatively simple outcome to measure systematically. Looking forward, Savinov is also interested in exploring fragment function outside inhibition, such as fragments that can stabilize the protein they bind to, enhance or alter its function, or trigger protein degradation.

Design, in principle

This research is a starting point for developing a systemic understanding of cellular design principles, and what elements deep-learning models may be drawing on to make accurate predictions.

“There’s a broader, further-reaching goal that we’re building towards,” Savinov says. “Now that we can predict them, can we use the data we have from predictions and experiments to pull out the salient features to figure out what AlphaFold has actually learned about what makes a good inhibitor?”

Savinov and collaborators also delved further into how protein fragments bind, exploring other protein interactions and mutating specific residues to see how those interactions change how the fragment interacts with its target.

Experimentally examining the behavior of thousands of mutated fragments within cells, an approach known as deep mutational scanning, revealed key amino acids that are responsible for inhibition. In some cases, the mutated fragments were even more potent inhibitors than their natural, full-length sequences.

“Unlike previous methods, we are not limited to identifying fragments in experimental structural data,” says Swanson. “The core strength of this work is the interplay between high-throughput experimental inhibition data and the predicted structural models: the experimental data guide us towards the fragments that are particularly interesting, while the structural models predicted by FragFold provide a specific, testable hypothesis for how the fragments function on a molecular level.”

Savinov is excited about the future of this approach and its myriad applications.

“By creating compact, genetically encodable binders, FragFold opens a wide range of possibilities to manipulate protein function,” Li agrees. “We can imagine delivering functionalized fragments that can modify native proteins, change their subcellular localization, and even reprogram them to create new tools for studying cell biology and treating diseases.”

News Team by — February 21, 2025 By News Team in Biotechnology Daily
How mosquitoes hear may inspire new ways to detect natural disasters

One of nature’s most disliked creatures may very well unlock a breakthrough in disaster response. A multidisciplinary Purdue University research team is recreating mosquito antennae to better study their sensitivity to vibrations. Should the research prove fruitful, it could lead to improvements in monitoring and detecting natural disasters such as earthquakes and tsunamis.

Research groups under Purdue professors Pablo Zavattieri and Ximena Bernal conducted this work, which is published in the journal Acta Biomaterialia.

“We’re still in the early stages but we’re pretty optimistic that we’ll at least learn a great deal,” said Zavattieri, the Jerry M. and Lynda T. Engelhardt Professor of Civil Engineering in Purdue’s College of Engineering. “Taking inspiration from nature and using it to advance scientific research has been a core feature of engineering since the very beginning.”

Despite lacking traditional ears, mosquitoes rely on their antennae to navigate the auditory landscape, homing in on crucial sounds amid the background noise of their own wingbeats.

Through analysis of the mosquitoes’ antennal features—particularly the arrangement and morphology of sensory hairs—civil and construction engineering Ph.D. candidate and team researcher Phani Saketh Dasika said they have already gained profound insights into how these adaptations enhance the auditory sensitivity and selective response to environmental cues.

“Using advanced micro-CT imaging to create high-fidelity CAD models for finite element analysis, we found that the architectural features of mosquito antennae enable species- and sex-specific acoustic target detection, even amid nontarget signals like their own wingbeats,” Dasika said. “Our findings also suggest that mosquito antennae are capable of detecting a broader range of frequencies than previously thought, though not all of these may be actively utilized.”

The team’s findings have provided key information for determining whether a mosquito’s antennae could inform the design of acoustic sensors.

“By modeling and contrasting the response of the antennae of species of mosquito using sound for different purposes, hearing mates or eavesdropping on frogs, we were able to tease apart features modulating hearing sensitivity and tuning,” said Bernal, a professor of biological sciences in Purdue’s College of Science. “Understanding how these structures work is the first step toward developing acoustic sensors inspired by their sensitive antennae.”

In terms of societal impact, insights from mosquito antennae could also inform the development of smart noise-canceling materials, Zavattieri said. These materials, potentially incorporating microfluidic channels or tunable metamaterials, could be used to create soundproofing panels for buildings, noise-canceling headphones or even acoustic cloaking devices.

News Team by — February 21, 2025 By News Team in Biotechnology Daily
HBV’s Ability to Infect Human Liver Cells Thwarted by Potential Anticancer Drug

As part of their effort to answer a decades-old biological question about how the hepatitis B virus (HBV) can establish an infection in liver cells, researchers led by teams at Memorial Sloan Kettering Cancer Center (MSK), Weill Cornell Medicine, and the Rockefeller University have identified a vulnerability that may open the door to new HBV treatments.

The team successfully disrupted the virus’s ability to infect human liver cells in the laboratory using a chromatin-destabilizing molecule CBL137, which is already in clinical trials against cancer. The results lay the groundwork for animal model studies and potential drug development.

Headed by chemical biologist Yael David, PhD, at MSK, working with hepatologist and virologist Robert Schwartz, MD, PhD, at Weill Cornell Medicine and Viviana Risca, PhD, at the Rockefeller University, the researchers reported on their findings in Cell, in a paper titled, “A nucleosome switch primes hepatitis B virus infection.”

Chronic HBV infection is an incurable pathogen responsible for causing liver disease and hepatocellular carcinoma, the authors wrote. “Over 325 million people worldwide are chronically infected by hepatitis B virus … leading to almost one million deaths annually despite the availability of effective vaccines.” Chronic infection leaves patients at risk for advanced liver disease, and HBV is estimated to cause nearly half of all hepatocellular carcinoma cases, the team continued.

The newly reported research began with a chance meeting and a longstanding paradox. Schwartz, an associate professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine, was introduced to David about six years ago at a retreat for Weill Cornell Physiology, Biophysics, and Systems Biology graduate school faculty, where they both hold appointments.

“On the surface, our research programs seem to have no overlap,” David said. “He studies hepatitis B, while my lab focuses on understanding how gene expression is regulated through a process called epigenetics. However, I was fascinated to discover that viruses like hepatitis B hijack epigenetic mechanisms, even using human DNA-packaging proteins to regulate their activity.”

Not long after, study first author Nicholas Prescott, PhD, then a doctoral student in the Tri-Institutional PhD Program in Chemical Biology, was preparing for a stint in the David Lab at MSK’s Sloan Kettering Institute. “His interest in epigenetic regulation in pathogens immediately made me consider HBV an ideal model system for him to explore,” David said.

At the heart of the mystery that intrigued the researchers lies a key viral gene that encodes for the HBV X protein (HBx). This protein is essential for HBV to establish a productive infection in host cells and the expression of its viral genes. However, the X gene itself is encoded within the viral genome.

“This raises a classic chicken-and-egg question that has puzzled scientists for decades,” David said. “How does the virus produce enough X protein to drive viral gene expression and establish infection?” The authors further commented “… HBx is absent from the virion and must be expressed de novo in freshly infected hepatocytes …”

Furthermore, the gene that encodes protein X is considered the virus’s oncogene—that is, the gene responsible for the disease’s progression toward cancer, Prescott added. That’s because protein X degrades proteins in the host that are involved with DNA repair. Not only does this keep the host from silencing protein X’s activity, but the infected cells are also more likely to accumulate DNA errors that build up over the years and decades, leading to the development of cancer.

“One of the main challenges with treating hepatitis B is that the existing treatments can stop the virus from making new copies of itself, but they don’t fully clear the virus from infected cells, allowing the virus to persist in the liver and maintain chronic infection,” noted Schwartz, whose lab contributed biological and clinical expertise in the virus, as well as the human liver cell models used in the study. “The current standard of care (long-term treatment with oral nucleos(t)ide analogs or short-term treatment with interferon-alpha injections) halts viral replication but falls short of eradicating cccDNA in infected hepatocytes, allowing the minichromosome to persist and sustain chronic infection,” the investigators stated. “Even with long-term antiviral treatment, basal levels of the HBV oncogenic X protein (HBx) remain in hepatocytes to promote genomic instability and disease progression.”

The hepatitis B vaccine is effective, but maintaining immunity often requires booster shots. Moreover, it doesn’t help people who are already infected. This happens, for example, due to transmission of the virus from mother to child, which is very common in developing countries. Access to vaccines and treatment is also more limited in some parts of Africa and Asia, where rates of infection are higher.

Digging into the mystery of protein X was a challenge, explained Prescott, who is now a postdoctoral fellow in the Laboratory of Chromosome and Cell Biology at the Rockefeller University. The existing tools weren’t capable of shedding light on what was happening in those critical early hours of an infection.

Early in infection, HBV establishes an independent “minichromosome” consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. But as the authors noted, “Despite extensive study, a significant knowledge gap remains regarding the role of viral chromatin status in establishing infection.”

The David Lab’s expertise is in how DNA gets packaged, read, and modified proved essential. For their newly reported research, the researchers successfully generated the HBV minichromosome for the first time, using their capabilities in reconstituting viral DNA in complex with human histones—the proteins that package and organize DNA. The research team determined that in order for protein X to get made, the hepatitis B virus’s DNA needs to get organized into DNA-histone complexes called nucleosomes. “… we generated recombinant, chromatinized cccDNA, allowing us to characterize its biophysical properties and to map nucleosome positioning on the minichromosome,” the scientists explained.

“This platform became a powerful tool not only to study the virus’s biochemistry but also to analyze, in detail, what happens in the critical first hours of an infection,” David said.

Nucleosomes are like beads on a string—the string is the viral DNA, and the beads are host-provided histone proteins, around which DNA gets wrapped; nucleosomes are the building blocks of chromatin, the material that makes up chromosomes.

It was this part of the project that tapped into the expertise of Risca at Rockefeller University. The Risca Lab studies the 3D architecture of the genome and how the packaging of DNA helps to control the transcription of genes. They had the tools and expertise to ensure that what the scientists were seeing in the new platform for studying the virus matched the reality of a human infection.

“Conventional wisdom says that packaging a gene’s DNA into nucleosomes would block or slow down the cell’s ability to read out that gene to make functional proteins, like protein X,” Risca commented. “But in complex organisms like humans and in the viruses that infect us, gene regulation is not always so straightforward. The presence and the positioning of nucleosomes on DNA can be important in directing cellular mechanisms to transcribe some genes. We found that to be the case for the HBV gene encoding protein X—the presence of nucleosomes on the viral genome is necessary for the transcription of RNA that gives rise to functional protein X.” The authors added. “Altogether, these data suggest a correlation between early cccDNA chromatinization and X transcription, which both occur during the first hours of infection.”

This discovery opens the door to understanding how the X gene is regulated and how HBV infection is established. Moreover, the researchers discovered a potential therapeutic opportunity. If it’s possible to disrupt the formation of these chromatin structures, then this could disrupt the virus’s ability to start and maintain an infection. “Given this link between chromatinization and transcription, we next hypothesized that disrupting chromatin assembly might inhibit viral transcription,” they wrote.

The team tested five small-molecule compounds known to impair chromatin formation. Only one, an anticancer drug candidate called CBL137, blocked production of protein X in liver cells.

Importantly, the compound worked in vitro at very low concentrations—many times smaller than participants in clinical trials for cancer were receiving, and using doses that only affected the virus, but not human cells. Their experimental results, they noted, “… demonstrate CBL137 as an effective inhibitor of HBV transcription and replication that may pose a potential therapeutic avenue to treat infections.”

David noted, “This made us very optimistic about the possibility of developing a treatment approach while preventing or limiting side effects. Moreover, if these results are confirmed through additional study, we are optimistic the approach could be used to treat chronic infections for the first time—and therefore could represent a potential cure.”

Additionally, CBL137 might prove similarly useful to target or study other chromatinized DNA viruses such as herpesviruses and papillomaviruses, the researchers noted. “Chromatin destabilization by CBL137 merits further investigation to test if it could prove similarly effective on other pathogens. Indeed, recent studies reported encouraging results for CBL137 as a latency reversing agent in HIV-1 infection and even a lead for drug discovery efforts against human African trypanosomiasis, underscoring its potential as a therapeutic against infectious diseases.

The project David pointed out, “…started from our fundamental interest in how the virus’s chromosomes might look and function and led to unexpected discoveries of how the viral infection is established in human cells.”

To further develop the team’s research toward a potential clinical trial, the next step would be to study the safety and effectiveness of CBL137 in animal models—though these are limited due to the narrow range of species HBV can infect, the researchers said.

All of the researchers stressed that the study wouldn’t have been possible without the close collaboration between the three institutions, which brought together the necessary expertise and technological resources—from MSK’s atomic force microscope to the Genomics Resource Center and High-Performance Computing Cluster at Rockefeller University.

Prescott commented, “This is a great example of how investment in ‘basic science’ and investigation of fundamental biological questions can open the door to medical advances,” he said. “I always thought I’d be working on questions that decades later someone might cite in a paper when they come up with a cure for some disease. Never in a million years did I expect to lead a project that identified such a strong candidate for drug development for a global scourge like hepatitis B.”

News Team by — February 21, 2025 By News Team in Bio Business News
Atrandi Raises $25M to Develop New Products Based on Semi-Permeable Capsule Tech

Atrandi Biosciences has raised $25 million in a Series A funding round led by Lux Capital, with participation from Vsquared Ventures, Practica Capital, Metaplanet, and CRIDS Capital. The company plans to use the funds to develop new products based on its semi-permeable capsule (SPC) technology as well as to set up an office in Boston which will allow the company to better serve its U.S. customer base.

Atrandi, which means “you discover” in Lithuanian, was launched in 2016 to address technological challenges associated with single-cell analysis. As Juozas Nainys, PhD, Atrandi’s CEO & co-founder, explained, the company was launched “to bridge a fundamental gap in biological research—the need for high-throughput, scalable technologies to manipulate and analyze single cells with precision.” Furthermore, “our SPC technology is a fundamental breakthrough born from a need to overcome the limitations of existing single-cell analysis tools, giving researchers the possibility to generate rich datasets with an unprecedented combination of throughput, multimodality and data quality.”

Atrandi will use some of the funds from its Series A to extend its offerings for DNA analysis from single cells, Nainys told GEN. The company already has a solution for microbial cells and expects to launch an option that works for eukaryotic cells later this year. They will be able to support whole genome analysis as well as more targeted analysis of single cells. Next year, Atrandi will focus on developing products for multi-omic analysis—specifically DNA and RNA analysis from single cells.

Designed for high-throughput single-cell research, Atrandi’s SPCs are aqueous compartments that are enclosed by a semi-permeable shell. They are designed to isolate single cells and nucleic acids while enabling the exchange of small molecules like enzymes and nutrients. The ability to exchange materials is an important part of SPCs value proposition for single cells and something that sets Atrandi’s technology apart from current droplet microfluidics technologies, according to Nainys. Typically, “once you form a droplet you can add reagents to it … but you can never remove [them],” he explained. “That’s very limiting [because] there are so many different molecular biology reactions that just do not work together or require specific pH [and] buffers.”

Nainys interest in single-cell technologies predates Atrandi’s founding. During his PhD, he worked in a laboratory focused on developing single-cell RNA sequencing technologies. “The single-cell revolution was really brought about by droplet microfluidics,” he said. “The lab that I joined specialized in droplet microfluidics and as experts in that particular technology, we saw that there are … a lot of things that can not be done in droplets.” That led him and Atrandi’s co-founders to launch the company in 2016 with an eye toward developing and commercializing SPCs as well as instruments for generating them.

To date, Atrandi has released three products based on its technology. The first of these is the Flux Microfluidic Device, a user-friendly system designed for high-throughput single-cell isolation into SPCs. The primary goal of this system was to “make the compartmentalization of the sample as seamless as possible so it’s really a push button,” Nainys said. “It’s more for a broader audience that doesn’t want to tinker with the technology.”

The two other products in Atrandi’s portfolio are the Onyx Droplet Generator, a microfluidic platform designed for high-throughput single-cell and single-molecule applications, and the Styx High-Throughput Screening Platform, which is designed for fluorescence-activated droplet sorting. These platforms are designed for users who want more control of their workflows and the ability to adjust different parameters as needed, Nainys said. They are compatible with SPCs as well as droplets. Additionally, “we also worked hard to make sure that the capsules integrate well with any readout method” including sequencing instruments, microscopy, and mass spectrometers.

So far, Atrandi has installed over 150 devices in labs in Europe, North America, and South Korea where they are used for a wide range of applications. About half of its customers are based in U.S. laboratories. People are using the solutions in different ways including studies in oncology, immunology, and microbiology, Nainys said. “It really is all over the map but at the end of the day it’s analyzing single cells as part of a complex biological system.”

News Team by — February 21, 2025 By News Team in Bio Business News
From farmland to construction: Bacteria strains offer sustainable biocement solution

A recent study examines the effectiveness of environmental strains for the production of biocement. The study’s lead author, Dimitrios Terzis, is an EPFL senior scientist and a co-founder of Medusoil, a company that produces organic binders and that opened a production plant in Vaud in 2024.

“For me, it’s essential to keep conducting fundamental research,” says Terzis, a civil engineer at EPFL’s Soil Mechanics Laboratory. His company Medusoil produces organic binders that are similar to biocement.

For the study published recently in Scientific Reports, Terzis worked with scientists from the University of Applied Sciences and Arts of Southern Switzerland to analyze 50 bacteria strains sourced from farmland in Ticino canton. This land is used for grazing dairy cattle and has shown to be particularly well suited for the production of Medusoil’s biocement due to the widely available presence of calcium.

Biocementation relies on stimulating a natural process: The secretion by microorganisms of an enzyme that triggers the formation of carbonate, which then binds with the calcium largely present in the soil to form calcite, a natural cement.

The study identified which naturally occurring strains fabricate the enzyme required for carbonate formation and can be fermented—two factors that make them prime candidates for biocement production. The scientists created a culture of the most promising strain, which was inoculated in a 1.5-meter-high column of sand.

After 24 hours of infiltration, the column was strong enough to sustain its weight and to be used in a variety of geotechnical engineering and geoenvironmental applications, like erosion. The scientists also found that using this strain could cut production costs by 40%.

A paradigm shift

Medusoil, founded seven years ago, supplies organic binders whose carbon impact is at least 55% lower than that of standard cement, which is made by heating an 80% limestone/20% clay mixture to high temperatures. Biocement can be used in a number of geotechnical and building applications, such as to reinforce dams, prevent soil erosion by wind and help protect areas subject to landslides, earthquakes or cyclic loads induced by road and railway traffic.

To test yet another application, the company’s biocement was used in a project in Geneva to recover concrete aggregates from demolished buildings. And because biocement can be employed several times, it supports the circular economy.

In the Scientific Reports study, the authors note that this naturally occurring biocementation process can be applied on a large scale and can help drive a paradigm shift towards greater sustainability in the construction industry.

New production plant

Medusoil reached a new milestone in 2024 with the opening of a production plant in Molondin, near Yverdon-les-Bains. “The plant can generate 400,000 liters of biocement per year, which is enough to stabilize five kilometers of riverbank against erosion,” says Vincent Laurençon, Medusoil’s head of manufacturing.

The company also has a mobile biocementation plant designed to make use of local raw materials. It was recently transported by truck to Romania, for example, where it was employed to reinforce roads. The firm intends to pursue its cutting-edge R&D and has projects lined up this year in France, the Middle East and the Netherlands.

News Team by — February 20, 2025 By News Team in Trending Now

Acting in the right place at the right time is the key to effective medical treatment with minimal side effects. However, this feat remains difficult to achieve.

Biologists and chemists at the University of Geneva (UNIGE) have succeeded in developing a tool that controls the location at which a molecule is activated by a simple pulse of light lasting only a few seconds. Tested on a protein essential for cell division, this system could be applied to other molecules.

The potential applications are vast, both in basic research and in improving existing medical treatments, such as those for skin cancer. These results are published in the journal Nature Communications.

Regardless of how it is administered, a medication does not only act on the affected organ but has a systemic effect on the entire body. This lack of precision carries risks: it may miss its target and not have the desired effect, or it may cause potentially serious side effects. In Switzerland alone, thousands of people suffer from severe drug-related side effects each year.

The solution, simple in theory but highly complex in practice, would be to activate drugs only at the location where they are needed. This challenging research task would, however, make it possible to activate or inactivate a protein in a living organism at a specific location to better understand its functions.

“Everything started from this methodological question,” recalls Monica Gotta, Professor in the Department of Cell Physiology and Metabolism at UNIGE Faculty of Medicine, who initiated and coordinated this research with Nicolas Winssinger, Professor in the Department of Organic Chemistry at UNIGE Faculty of Science.

“We were looking for a way to inhibit a protein involved in cell division, the Plk1 protein, when and where we wanted, to better understand its function in the development of an organism.”

Breaking a biological lock

By combining their expertise in chemistry and biology, the scientists were able to modify a Plk1 inhibitor molecule so that it would be activated by a pulse of light.

“After a complex process, we were able to block the active site of our inhibitor with a coumarin derivative, a compound naturally present in certain plants. This coumarin could then be removed with a simple light pulse,” explains Victoria von Glasenapp, a postdoctoral researcher in the laboratories of Professor Gotta at the Faculty of Medicine and Professor Winssinger at the Faculty of Science, and first author of the study.

The challenge was still to find a way to anchor the inhibitor at the exact point in the body where its action was desired. “We thus modified the inhibitor so that it becomes trapped in the targeted cell by adding a molecular anchor that is released only by light,” explains Nicolas Winssinger.

“This enabled us to activate and anchor the inhibitor with the same light pulse, thereby inactivating Plk1 and stopping cell division at the precise desired location.”

Countless possible applications

The system developed by the UNIGE scientists makes it possible to spatially and temporally control the activity of a molecule in a living organism using light. It can be adapted to numerous molecules to be able to activate a drug only where it is needed.

In the future, a simple laser could therefore activate a treatment exactly where it is needed while sparing the surrounding healthy tissue, thereby limiting undesirable side effects.

“We hope that our tool will be widely used, leading to a better understanding of how living organisms function and, in the long term, to the development of location-specific treatments,” concludes Gotta.

News Team by — February 20, 2025 By News Team in Trending Now
Arc Institute’s AI Model Evo 2 Designs the Genetic Code Across All Domains of Life

“Today, we can for all practical purposes read, write, and edit any sequence of DNA, but we cannot compose it. Maybe we can cut and paste pieces from nature’s compositions, but we don’t know how to write the bars for a single enzymatic passage. However, evolution does.” —Frances Arnold, PhD (Nobel Prize Lecture 2018)

Evo, the genome foundation model developed by the Arc Institute published last November that generalizes across the languages of biology — DNA, RNA, and proteins for both predictive and generative capabilities — has received a major update.

In a new preprint that is not yet peer-reviewed and first published on Arc’s website, Evo 2 moves beyond single-cell genomes of bacteria and archaea to include information from humans, plants, and other more complex single-celled and multi-cellular species in the eukaryotic domain of life.

The model’s resulting research applications span a diverse array of scientific fields including drug discovery, agriculture, industrial biotechnology, and material science. The multimodal and multiscale work is a collaboration with Nvidia along with contributors from Stanford University, UC Berkeley, and UC San Francisco.

“The recipe for life is entirely present in the genetic information contained in our DNA,” said Kimberly Powell, vice president of healthcare at Nvidia. “We’re seeking a deeper understanding of biological complexity. Evolution has solved this problem over millions of years, and Evo 2 aims to learn from this knowledge.”

In healthcare, understanding which gene variants are tied to a disease is an invaluable tool for therapeutics. Early validation of Evo 2’s capabilities showed that the model can identify how genetic mutations affect protein, RNA, and organismal fitness. In tests with variants of BRCA1, a gene associated with breast and ovarian cancer risk, Evo 2 achieved greater than 90% accuracy in predicting which mutations are benign versus disease-causing. 

Patrick Hsu, PhD, Arc Institute co-founder and an assistant professor of bioengineering at UC Berkeley, stated that Evo 2 is the only model that can predict the effects of both coding and noncoding mutations.

“It is the second-best model for coding mutations, but it is state-of-the-art for noncoding mutations, which other variant effect prediction methods, such as AlphaMissense from DeepMind, cannot score,” said Hsu. 

Hsu also described Evo 1 as a “blurry picture of single-cell life” because it was trained on a corpus of 300 billion nucleotides derived from prokaryotic genomes. The team “wanted to be much more ambitious” in this collaboration with Nvidia. 

Evo 2 was built on NVIDIA’s DGX Cloud platform and is trained on more than 9.3 trillion nucleotides from the genomes of more than 128,000 species across the tree of life. The model uses a novel architecture called StripedHyena 2, which enabled training that was “nearly three times faster than optimized transformer models,” according to Dave Burke, PhD, chief technology officer at Arc Institute. The model also has 40 billion parameters and is similar in scale to the current generation of large language models released from Meta, DeepMind, or OpenAI. 

Evo 2 can process DNA sequences of up to 1 million nucleotides at once, allowing it to understand relationships between distant parts of the genome. Hsu stated that this long context length unlocks multiple molecular scales, from short biological molecules, such as tRNA, or clusters of genes (e.g., operons), to entire bacterial genomes or eukaryotic chromosomes. 

Arc Institute and Nvidia describe Evo 2 as the “largest publicly available AI model for biology to date.” Evo 2 is available for public use on the NVIDIA BioNeMo platform and as an interactive user-friendly interface called Evo Designer. In addition, the authors have made its training data, training and inference code, and model weights open source. 
Biology’s app store Understanding biology as a “language” is not a new concept. Advances in genome sequencing have allowed us to “read” the human genome, while the invention of CRISPR technology expanded our toolbox to gene “editing.”  

In 2023, Hsu and Brian Hie, PhD, assistant professor of chemical engineering at Stanford University, began thinking about designing or “writing” biological sequences, including proteins, by starting at the foundational layer of DNA itself. “After all, proteins themselves are encoded directly by the genome,” emphasized Hsu.  

“Machine learning started to revolutionize biology, and models such as AlphaFold or ESMFold enabled protein structure prediction and design. Despite these advances, the complexity of these molecules is dwarfed by the overall complexity of an entire cell,” Hsu continued. 

Given that biological functions are not accomplished by a single protein molecule in isolation, constructing synthetic genomes can provide a valuable research tool to investigate broader biological context, a feat that Evo 2 is tackling head-on. 

“A lot of biological design until now has focused on the molecular level because that’s all that we could control. If we have a powerful model that lets us generate at the scale of complete organisms, then that unlocks a lot of downstream tasks [with a wide array of use cases],” said Hie. 

The Evo 2 preprint described three design tasks that span different levels of genomic complexity: 1) mitochondrial genome 2) prokaryotic genome of Mycoplasma genitalium, a commonly used model of the minimum genome, and 3) yeast chromosome, which represents eukaryotic organisms.

For all three design tasks, the preprint showed evidence supporting genome coherence, such as the construction of genes that code for all the components of the electron transport chain (as predicted by AlphaFold 3) in the case of the mitochondrial genome, and the presence of natural homologs and more complex genomic architecture, such as introns, in the case of the yeast chromosome. 

The preprint also presented a workflow for “generative epigenomics,” which designed DNA sequences with desirable chromatin accessibility profiles to simulate eukaryotic gene regulation.  

When asked about plans for experimental validation, Hie stated that a collaboration with large DNA synthesis and assembly experts from the University of Washington is underway to insert the chromatin accessibility designs into mouse cells for validation studies. 

Looking ahead, the Arc Institute is interested in building on this biological complexity by constructing the virtual cell.  

“The bottleneck to drug discovery is that we don’t know what causes the disease to begin with,” said Hie. “If we have a very capable model of the genome and we couple this with information from the environment through RNA sequencing, gene regulatory networks, and cell signaling networks, then this combined multimodal framework will let us answer these fundamental questions about disease.”

Hie sees Evo 2 as an “operating system”, or a foundational layer, that provides a platform for broad generative functional genomics. While Evo 2 “might not solve all questions in biology,” the model offers a wider breadth of applicability compared to task-specific predecessors, such as AlphaFold for protein structure prediction. 

“We want to empower the research community to build on top of these foundation models. That’s why we put in so much effort with Nvidia to make this fully open source,” weighed in Hsu. “We’re really looking forward to how scientists and engineers build on this ‘app store’ for biology.” 

News Team by — February 20, 2025 By News Team in Biotechnology Daily
Accelerating mRNA Vaccine Production

In principle, mRNA vaccines are ideal for health emergencies as they can be quickly mass produced using a template. The problem is that current cell-based template production methods take too long, says pandemic preparedness organization, CEPI.

And slow template production limits access to vaccines, according to Chaminda Salgado, CMC technology lead, who told GEN about CEPI’s efforts to develop an alternative with French technology firm, DNA script.

“While the process of producing mRNA itself takes only around seven days, the creation of a DNA template can take up to a month, creating a bottleneck in the manufacturing process. That’s because creating a DNA template typically involves living organisms, such as bacteria or yeast, to grow, extract, and purify the required DNA plasmid templates.

“This new project aims to overcome these challenges by generating automated synthetic DNA templates, which don’t need to be grown in living cells and can be rapidly produced within days rather than weeks, without the need for expensive biopharmaceutical facilities or highly trained staff to run the process,” Salgado says.

The plan is to take DNA oligonucleotides made using DNA Script’s enzyme driven synthesis technology—called Syntax—and combine them into longer template sequences using an automated “gene assembler” system.

Manufacturing cost

Replacing cell culture-based template production with synthetic methods could have a significant impact on manufacturing cost and timelines, according to Salgado.

“By streamlining the process, mRNA vaccines could be manufactured and developed even faster and cheaper, meaning vaccines could be given to at-risk populations sooner and potentially help to stop an outbreak in its tracks.

“This technology supports CEPI’s 100 Days Mission—a goal to produce pandemic-busting vaccines within 100 days of a viral threat being identified—and complements a suite of CEPI investments aiming to increase the speed at which vaccines can be manufactured,” he adds.

Another aim of the partnership is to make it easier for people to access vaccines by enabling production in areas without an established manufacturing infrastructure.

Salgado says, “This partnership supports equitable access as it reduces the need for expensive pharmaceutical equipment and infrastructure associated with traditional biologically manufactured DNA templates.

“If successful, the lower costs associated with automated, synthetic DNA template production would remove a potential barrier to the introduction of the technology in Global South countries where resources may be more limited. This could enable the possibility of vaccination closer to the site of an outbreak and avoid delays in vaccine access.”

CEPI and DNA Script are also committed to enabling equitable access to the outputs of the collaboration, Salgado says, adding, “This ultimately includes a commitment to vaccines being available first to populations at risk when and where they are needed at an affordable price should a related vaccine be developed further using CEPI funding.

“Project results, including data generated as part of this project, will be published open access for the benefit of the global scientific community.”

News Team by — February 20, 2025 By News Team in Biotechnology Daily
Cholesterol Metabolite Implicated in Parkinson’s Disease Pathology

Researchers at Wuhan University have discovered a cholesterol metabolite that may play a critical role in the development of Parkinson’s disease (PD). Studies in mice, led by Zhentao Zhang, MD, PhD, indicated that the metabolite, 24-hydroxycholesterol (24-OHC), promotes the spread of Lewy bodies and the death of dopaminergic neurons in the brain, the two major hallmarks of Parkinson’s disease. 24-OHC is produced from cholesterol by the actions of an enzyme, cholesterol 24-hydroxylase (CYP46A1), and the researchers suggest that blocking the activity of 24-OHC or preventing the metabolite from being produced could potentially represent effective strategies for treating Parkinson’s disease.

Zhang and colleagues reported on their findings in PLOS Biology, in a paper titled, “The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkinson’s disease.”

PD is the second most common neurodegenerative disease, and leads to slowness of movement, tremor, rigidity, cognitive impairment, and neuropsychiatric symptoms, the authors explained. The disease is characterized by the formation of Lewy bodies composed of aggregates of α-synuclein (α-Syn), and death of dopaminergic neurons in the substantia nigra.

“Converging lines of evidence indicate that α-Syn fibrils can spread in a prion-like manner in the brain, leading to self-propagation and cell-to-cell transmission of protein aggregate,” the investigators stated. “Although it is clear that α-Syn aggregation underlies the pathology of PD, what drives the spread of α-Syn remains unclear.”

Their newly reported study was designed to investigate what causes the spread of pathological α-Syn, with the authors hypothesizing that the culprit is the cholesterol metabolite 24-OHC, which is known to present at high levels in the brains of people with Parkinson’s disease, and which increases with age. “Various types of clinical evidence indicate that the levels of 24-OHC in the cerebral spinal fluid (CSF) are increased in PD patients and are correlated with the duration of the disease,” they wrote, also commenting that “previous studies demonstrate cholesterol 24-hydroxylase (CYP46A1) increases the risk for PD.”

Through their study, the team first confirmed that 24-OHC levels were higher in the blood of patients with Parkinson’s disease as well as in a mouse model of the disease. The results, they wrote, “… suggest that both CYP46A1 and 24-OHC increase in an age-dependent manner and are elevated in PD patients, PD model mice, and aged wild-type mice.”

The researchers then blocked 24-OHC production in the mouse model by knocking out the CYP46A1 enzyme. This reduced both the spread of the harmful α-Syn fibers and damage to the dopamine neurons in the critical part of the brain. “… CYP46A1 knockdown relieves the spread of α-Syn pathology and the loss of dopaminergic neurons,” they commented.

Further experiments with neurons cultured in a dish showed that the addition of 24-OHC caused normal α-Syn to change into harmful α-Syn fibers. Injecting mice with these fibers led to a greater spread of Lewy bodies, more dopaminergic neuron degeneration, and greater motor deficits than did injecting them with α-Syn fibers formed in the absence of 24-OHC. The researchers suggested that drugs that prevent cholesterol from being converted to 24-OHC might therefore be an effective treatment for the disease.

The authors suggest that their findings “… indicate that the cholesterol 24-hydroxylase CYP46A1 plays a pivotal role in the progression of α-synuclein pathology in Parkinson’s disease, highlighting its potential as a therapeutic target for Parkinson’s disease.” In their report, they further stated, “It will be interesting to determine whether CYP46A1 and 24-OHC can serve as theranostic biomarkers for disease-modifying therapies.”

News Team by — February 20, 2025 By News Team in Bio Business News
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