The work comes from researchers at the Icahn School of Medicine at Mount Sinai, who report that non‑immune cells—including muscle fibers and hepatocytes—play a decisive role in determining mRNA vaccine potency. Their paper, “mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression,” was published today. The findings overturn a long‑held assumption that mRNA vaccines must deliver their payload to dendritic cells to prime strong T‑cell responses.

“This study fundamentally changes how we think mRNA vaccines work,” said senior author Brian D. Brown, PhD, director of the Icahn Genomics Institute. “For years, the field has assumed that getting the mRNA into dendritic cells, the immune cells that activate T cells, was essential. We show that’s not the case. These cells are still important, but mRNA delivery to them is not required.”

To dissect how different cell types influence immunity, the team used a microRNA‑based technology developed in Brown’s lab that allows researchers to “turn off” mRNA expression in specific cell populations. By incorporating short microRNA target sequences into the mRNA, they selectively silenced expression in dendritic cells, hepatocytes, or muscle cells while leaving other tissues unaffected.

The results were striking. Silencing mRNA expression in dendritic cells did not impair T‑cell priming, including for SARS‑CoV‑2 antigens, suggesting that cross‑presentation by other cell types is sufficient to initiate immunity. “This was unexpected,” said Brown. “It tells us that other cells are producing the vaccine antigen and handing it off to the immune system.” In contrast, turning off expression in muscle fibers weakened the immune response, while turning off expression in hepatocytes tripled it.

“We found that hepatocytes actively dampen the immune response to mRNA vaccines,” said Sophia Siu, an MD/PhD student and co‑lead author. “This is notable because hepatocytes can take up a lot of mRNA, particularly when it’s injected intravenously. For vaccines, we discovered that we don’t want expression in hepatocytes. However, for mRNA therapeutics, hepatocyte expression can be beneficial because it may help prevent immunity to the mRNA-encoded protein.”

“In mice bearing tumor-associated antigen (TAA)-expressing lymphoma cells, miRT-mediated hepatocyte-silenced TAA mRNA vaccine enhanced immune response and reduced tumor burden,” wrote the authors. The approach also reduced hepatocyte death when mRNA was used to boost pre‑existing T cells, an important consideration for gene‑editing and CAR T–related applications.

“These results show that we can make mRNA cancer vaccines more effective simply by controlling where the mRNA‑encoded antigen is expressed,” said Joshua D. Brody, MD, director of the Lymphoma Immunotherapy Program at the Mount Sinai Tisch Cancer Center. “It’s a new lever for improving immunotherapy.”

Beyond oncology, the findings could influence the design of mRNA‑based vaccines for infectious diseases and therapeutics for autoimmune and genetic disorders. By tuning expression in specific cell types, researchers can amplify or dampen immune responses as needed.

“mRNA technology is transformative for medicine,” Brown said. “Our work provides a new set of design rules for mRNA vaccines and therapeutics. As this technology continues to evolve, understanding and controlling where mRNA is expressed will be critical.”

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“As tumors progress, cancer cells leave the original site and spread or metastasize to other organs where they seed new tumors,” said Xiang Zhang, PhD, William T. Butler, MD, Endowed Chair for Distinguished Faculty, professor of molecular and cellular biology, and director of the Lester and Sue Smith Breast Center at Baylor. “Our lab is interested in better understanding what cellular and molecular features support metastasis as these could guide the development of therapies to prevent, slow down, or eliminate them. In the current study, we first developed a new method to identify the makeup of metastatic niches.”

Zhang, also a member of Baylor’s Dan L Duncan Comprehensive Cancer Center, is senior and corresponding author of the team’s published paper in Cell, titled “Unbiased niche labeling maps immune-excluded niche in bone metastasis.”

During metastasis, cancer cells interact constantly with other normal cells in the body, and these interactions affect cell behavior, fate, and even response to therapies. “Numerous previous studies have elucidated the roles of specific microenvironment niches (i.e., cells that are immediately adjacent to cancer cells) in the progression of metastasis,” the authors wrote.

For their newly reported study the team developed the SAMENT technology. “Our method allowed us to identify specific cells encountered by cancer cells during metastasis,” said co-first author Fengshuo Liu, graduate student in the Cancer and Cell Biology Program working in the Zhang lab. “The method, called Sortase A–Based Microenvironment Niche Tagging (SAMENT), selectively labels normal cells that come into direct contact with cancer cells.”

The authors further explained, “By combining SrtA and synthetic ligand-receptor binding, we aim to label any cells that are physically encountered by cancer cells.”

The investigators’ tests using SAMENT revealed that pro-metastatic microenvironments of multiple cancer models in all the organs studied, including bone, lung, liver, and brain, shared common features, including an abundance of macrophage immune cells and shortage or absence of immune T cells, which typically help fight tumors. “Among all cell types, macrophages occur most frequently surrounding disseminated cancer cells and appear to be phenotypically re-programmed upon interaction with metastases,” they wrote.

Liu added, “However, bone metastases stood out. We were surprised to find that macrophages surrounding cancer cells in bone metastases activated a protein called estrogen receptor alpha (ERα). This protein is best known for its role in hormone-responsive breast cancer but is much less studied in macrophages or other immune cells.” The team added, “It also plays an important role in many other cell types, including macrophages, T cells, osteoblasts, and osteoclasts.”

The study showed that macrophages with active ERα signaling were not detected in normal bone or in primary tumors in other tissues. ERα-active macrophages were also present in human bone metastasis samples from patients with breast, lung and kidney cancers—including male patients. This showed that this finding is not limited to one cancer type or to women.

The researchers also investigated how cancer cells turned macrophages, which would typically fight cancer, into their allies. Cancer cells deliver small molecules called fatty acids (FAs) to macrophages, likely through tiny particles known as extracellular vesicles (EVs). These fatty acids activate a metabolic pathway in macrophages that turns on ERα signaling. “Taken together, our data indicate that ERα expression in macrophages is driven by cancer cell-derived FAs through paracrine interaction mediated by EVs,” they wrote.

Once ERα is active, macrophages become immunosuppressive—instead of helping the immune system attack cancer, they form a barrier that physically and chemically blocks T cells from reaching tumor cells. ERα-active macrophages act as bodyguards for metastatic cancer in bone.

“To test whether ERα in macrophages can drive bone metastasis, we genetically removed the ERα gene specifically from macrophages in mice,” Liu continued. “As a result, cancer cells were far less able to colonize bone in multiple cancer models. Tumors grew more slowly, and metastases in other organs that often arise from bone tumors were also reduced. Importantly, removing ERα from macrophages did not disrupt normal bone health—bone structure and remodeling remained intact.” In their paper the scientists stated, “Taken together, our results strongly support the hypothesis that ERα in macrophages plays an important role in bone colonization.”

“When macrophage ERα was genetically removed or when mice were treated with fulvestrant, an FDA-approved cancer drug that degrades estrogen receptors, T cells were able to enter metastatic lesions in bone and kill tumor cells,” Zhang said. “Our findings support conducting future human clinical trials to assess the value of estrogen-blocking therapies combined with other therapies to treat bone metastases across multiple cancer types, in both women and men.”

The authors added, “Furthermore, as shown in the final set of experiments, inhibition of ERα in macrophages may not be effective by itself but could synergize with immunotherapies because it facilitates T cell infiltration into static lesions.” The team acknowledged that they didn’t see any synergy between Erαknockout in macrophages and anti-PD1 treatment. However, they noted, “… it is still worth exploring the combinatory effects with other immunotherapies. Therefore, our findings may warrant future clinical trials on combined endocrine and immunotherapies on patients with bone metastases, and this combination may be extended to other cancer types and to patients of both genders.”

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As global efforts continue to expand manufacturing infrastructure and advance technology transfer, WHO is placing equal emphasis on the people and systems required to make these investments sustainable and impactful.

The designation follows a global selection process conducted through two calls for expressions of interest and forms part of the WHO Biomanufacturing Workforce Training Initiative established in 2023. This flagship effort addresses critical skills gaps across the biomanufacturing value chain, enabling countries to translate technological advances into sustainable local production.

“Building a skilled biomanufacturing workforce is fundamental to advancing equitable access to health products and strengthening global health security. By designating regional training centers across all WHO regions, we are investing in people and systems that enable countries not only to produce quality-assured essential health technologies, but to sustain and scale them,” said Yukiko Nakatani, MD, PhD, WHO assistant director-general for health systems, access, and data. “This network reflects a strategic shift towards more resilient, geographically diversified manufacturing capacity, grounded in science and collaboration.”

The newly designated regional training centers will operate as part of a coordinated global network, delivering context-specific training aligned with regional priorities, regulatory environments and languages, according to Nakatani. By partnering with academia and industry, they plan to expand access to training, strengthen regional expertise and foster collaboration across countries, supporting the development of a skilled and sustainable workforce. While operating independently, they will work in close collaboration with WHO under agreed frameworks to ensure quality, alignment, and accountability, note WHO officials.

The selected institutions are:

• African Region: Institut Pasteur de Dakar, Senegal; Council for Scientific and Industrial Research, South Africa
• Region of the Americas: Oswaldo Cruz Foundation (Fiocruz), Brazil
• South-East Asia Region: Translational Health Science and Technology Institute, India
• European Region: National Institute for Bioprocessing Research and Training, Ireland
• Eastern Mediterranean Region: Center for Continuing Professional Development, Egyptian Drug Authority, Egypt Western Pacific Region: Peking University, China

These centers will complement the Global Training Hub for Biomanufacturing (GTH-B), established in 2022 in collaboration with the Ministry of Health and Welfare of the Republic of Korea.The Global Hub delivers standardized training programs that combine hands-on experience and classroom-based learning, while also supporting the WHO initiative through training-of-trainers programs.

The WHO Biomanufacturing Workforce Training Initiative was designed to directly support the implementation of World Health Assembly resolution WHA74.6 on strengthening local production of medicines and other health technologies. By investing in workforce development, WHO states that it is helping to address longstanding inequities in access to health products and to ensure that all countries are better equipped to respond rapidly and effectively to future health emergencies.

As global health systems move from crisis response to long-term resilience, building a skilled and geographically distributed biomanufacturing workforce is emerging as a cornerstone of pandemic preparedness and health security, points out a WHO spokesperson.

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According to Serif Biomedicines, a five-year-old startup that emerged from stealth mode this month, the result is “modified DNA,” a new class of therapeutics designed to be programmable, durable, scalable, and redosable—while minimizing the drawbacks of both mRNA and gene therapy.

Modified DNA builds upon generative protein and mRNA platforms created by Flagship Pioneering, the venture capital giant which founded Serif in 2021. On April 21, Flagship formally launched Serif with an initial commitment of $50 million in financing—capital that Serif intends to use toward developing its scalable platform for optimizing and manufacturing Modified DNA treatments, aided by artificial intelligence (AI), and advancing its first drug discovery programs.

“The reason we’re bringing the company out of stealth mode now is we think we have made progress. We’ve made real progress that we’re excited to share with the world, that we’re excited to get feedback from the broader scientific community on, and we want to tell that story more broadly,” Jacob (Jake) Rubens, PhD, Serif’s co-founder and CEO, and an Orig­i­na­tion Part­ner at Flag­ship Pio­neer­ing, told GEN.

“It’s been on our minds for a long time: What might be possible when DNA becomes an engineerable biotechnology for the first time?”

It’s a question pursued by numerous researchers and companies over the years as they sought to capitalize on DNA’s qualities of being a durably expressing molecule capable of coding for any gene, producing proteins or RNAs in a cell-specific way, as well as being scalable to manufacture and capable of re-dosing for patients.

“Those are, I think, the key differentiating attributes of theoretical DNA medicines. So the question for us became not, would this be valuable if we could do it, but why hasn’t anyone done it yet?” Rubens explained. “We’ve known about the centrality of DNA in biology, the central information molecule in DNA. We’ve known this for 75 years since Watson and Crick’s seminal discoveries around how the structure of DNA enabled it to function as an information molecule.”

Two key problems

“And when we looked at this space,” he continued, “we saw that there were two key problems: The first is that DNA is a highly inflammatory molecule. The second is that DNA needs to be delivered not just into a cell, but into the nucleus, the center of the cell.”

To create Mod­i­fied DNA, Serif alters the struc­tur­al and chem­i­cal form of DNA in order to min­i­mize innate immuno­genic­i­ty as lipid nanoparticles drop off the DNA not in the nucleus, but in the cytoplasm of the cell.

Once inside the cell nucleus, Mod­i­fied DNA reverts to unmod­i­fied DNA, enabling tran­scrip­tion into ther­a­peu­tic RNA and proteins. The resulting treatments are designed to last longer, be giv­en more than once, and be pro­grammed for cell-spe­cif­ic expres­sion. To enhance durability, Serif delivers with its Mod­i­fied DNA proteins which help the DNA access the nucleus. The proteins, called mRNA co-fac­tors, are designed to tran­sient­ly express pro­teins that enhance entry into the nucleus and gene expression.

Pending an announcement it expects to make later this year, Serif isn’t revealing specifics of its initial drug discovery programs, except to say that they focus on rare diseases and immune programming.

“This is not meant to be a limited list of where we could go but the areas that we think we’re going to go first, which are likely in addressing protein deficiencies in genetic diseases,” Rubens said.

Modified DNA has shown itself to be disease agnostic, he added, reflecting DNA’s qualities as a general, programmable information molecule: “One of the reasons we’re so excited about, the future of modified DNA as a new biotechnology akin to RNA, akin to protein, is its centrality in biology. It is the fundamental information molecule inside of all of us, inside of every living thing on this planet. So that is really the existence proof that it is generalizable.”

Tolerability and sustained expression

Also later this year, Serif plans to present data at an as-yet-unspecified scientific conference that will show modified DNA’s tolerability in non-human primates, as well as sustained gene expression with therapeutic effects in preclinical models following intravenous (IV) administration.

Serif aims to transform Modified DNA into treatments as effectively and commercially successfully as Amgen, Genentech (now a member of the Roche Group), and later Regeneron did with engineered proteins, as Alnylam Pharmaceuticals did with small interfering RNA (siRNA), and as Moderna more recently accomplished with mRNA—most notably in developing its SpikeVax^® COVID-19 vaccine, which the FDA authorized for emergency use in 2020 and fully approved in 2022.

Flagship launched Moderna in 2010; the company went public in 2018 by raising $604 million, the largest-ever U.S. biotech initial public offering (IPO) until Kailera Therapeutics raised $625 million earlier this month.

At Flagship, Rubens is a sci­en­tist entre­pre­neur who leads the firm’s Pio­neer­ing Busi­ness Unit, which establishes and grows com­pa­nies based on new biotechnology. In addition to Serif, Rubens co-founded Quo­tient Ther­a­peu­tics, which develops therapies based on its somatic genomics platform; Tessera Ther­a­peu­tics, which writes therapeutic messages into the genome through a genome engineering approach called GeneWriting; and Sana Biotech­nol­o­gy, a developer of treatments based on engineered cells. He also launched Kalei­do Bio­sciences, a microbiome therapeutics company that ceased operations in 2022.

Before join­ing Flagship, Jake received his PhD in micro­bi­ol­o­gy from MIT, work­ing with Tim Lu, MD, PhD, a core member of the Synthetic Biology Center, through the sup­port of a Nation­al Sci­ence Foun­da­tion Grad­u­ate Research Fel­low­ship. At MIT, Jake helped enable ​“intel­li­gent” cell therapies by invent­ing gene cir­cuits that allow engi­neered cells to do nov­el ana­log, dig­i­tal, and hybrid com­pu­ta­tions.

Based in Cambridge, MA, Serif employs about 50 people and as of Wednesday was disclosing five open positions on its website in its three areas of focus: Chemistry (associate scientist and senior scientist, both specializing in LNP formulations), Molecular Biology (research associate and senior scientist), and Research/Discovery (scientist specializing in bioanalytical assays).

“I’m not at this point going to provide any guidance on how much more we will or won’t grow,” Rubens said. “We’re quite agile and responsive to the company’s needs.”

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Transactivation domains (TADs) of transcription factors are enriched in intrinsically disordered regions (IDRs) that lack a stable three-dimensional structure. The plasticity of an IDR permits dynamic conformations that regulate cellular and biological functions. 

The new study developed inhibitors that bound to the TADs of the androgen receptor, a therapeutic target for prostate cancer. While therapeutic interventions often target its folded ligand-binding domain (LBD), resistance ultimately develops due to reactivation of androgen receptor signaling. 

Inhibitors stabilized the protein in the inactive state to prevent the activation of genes that drive cancer growth. In animal studies, several compounds slowed prostate cancer growth more effectively than a commonly used prostate cancer treatment. Notably, several antigen receptor TAD inhibitors displayed strong binding affinities higher than, or were comparable to the LBD-inhibitor enzalutamide, with dissociation constants in the picomolar to low-nanomolar range 

“Most drug discovery is like designing a key for a very specific lock,” said Marianne Sadar, PhD, professor of pathology and laboratory medicine at the UBC faculty of medicine, distinguished scientist at BC Cancer, and co-corresponding author of the study. “But disordered proteins don’t behave like locks at all, they’re more like moving strands of spaghetti.”   

“This study shows that proteins previously thought to be undruggable can be drugged with remarkable efficacy,” she continued. “The findings could have profound implications for the treatment of cancer and other diseases, providing a roadmap for the development of new treatments.”   

“What surprised us was how effectively these molecules could attach to a protein that doesn’t have a fixed structure,” said Raymond Andersen, PhD, professor in UBC’s department of chemistry and co-corresponding author of the study. “We were able to shut down the androgen receptor even in situations where current prostate cancer drugs stop working.”   

The researchers now aim to advance the most promising candidates toward clinical trials, with the goal of developing prostate cancer drugs for early intervention and with fewer side-effects.  

“If the approach continues to prove successful, it could dramatically expand the number of proteins that scientists can target with medicines—turning what was once considered a dead end into a promising new frontier for drug discovery,” said Sadar. 

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Spheroids can be useful to model complex human tissues because they can re-create specific cell-to-cell and cell-to-matrix interactions. But spheroids are fragile, and common techniques for moving them manually—via suction—can easily damage them. In tissue engineering, the tiniest bit of improper force can harm a living culture. Now, a force-sensing miniature robot—a mobile microgripper (MMG)—has been developed that can handle spheroids with care.

“Other techniques for cell spheroid bioassembly can affect the tissue construct and/or apply limited manipulation forces,” said David Cappelleri, PhD, professor of mechanical engineering and assistant vice president for Research Innovation School of Mechanical Engineering at Purdue University. “The force-sensing MMG presented here addresses these current issues by allowing the safe bioassembly of different spheroids into a single construct.”

This work is published in APL Bioengineering, in a paper entitled, “Force-sensing mobile microrobotic grippers for gentle and precise bioassembly of cell spheroids.”

Integrating different types of spheroids into one culture is key for tissue engineering. But individual spheroids have to be grown in place and then moved around, introducing the chance of damage to the spheroid.

The MMG is a microscopic robot made of two arms connected by a hinge for a controlled—and gentle—gripping. Also, it is controlled by magnets, which are biocompatible with spheroids, decreasing the risk of collateral damage.

“This was a big part of the design—figuring out a way to use magnetic fields for both locomotion and for controlling the opening and closing of the gripper jaws,” Cappelleri said.

The gripping force is monitored and adjusted in real time, allowing researchers to adapt to the delicate nature of the cells. After simulating the efficacy of the MMG, in vitro testing showed that the device was able to successfully move and organize spheroids into neat patterns.

The researchers also verified that the range of gripping forces exerted by the MMG was compatible with the movement and subsequent survival of the spheroids.

Currently, the robot can successfully assemble the spheroids in a cellular “sheet,” but in the future, the researchers want to use their tiny robots to create full engineered tissues. In addition, the researchers want to take their microgrippers a step further, transitioning from manual control to automated spheroid assembly.

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A new study from the Gladstone Institutes aims to change that. In a large, nine‑lab collaboration, researchers have translated a retron‑based DNA editing system from E. coli into 14 additional bacterial species spanning three major phyla. The work, published in Nature Biotechnology and titled “Genome editing of phylogenetically distinct bacteria using cross-species retron-mediated recombineering,” demonstrates that retrons, bacterial immune elements that continuously produce short DNA strands, can be engineered into portable genome editing modules the authors call recombitrons. “Recombitrons—a genome editing tool created by pairing modified, donor-producing bacterial retrons with single-stranded binding and annealing proteins—have increased the efficiency of recombineering to install flexible, precise edits in the prokaryotic chromosome,” the authors wrote.

Retrons normally function as part of a viral defense system, generating DNA fragments that help bacteria detect and respond to infection. Seth Shipman, PhD, a Gladstone Investigator and senior author of the study, has spent years repurposing this machinery. “We’ve been easily editing E. coli genomes using retrons for years now, which has substantially increased the pace of our fundamental biology and our molecular technology development,” he said. “But we kept hearing from the broader field, asking when there would be a version of this technology that could be put to work in other bacterial species that matter for the environment, industrial processes, or human health.”

Shipman’s lab previously showed that retrons can act as cellular DNA-making factories, generating the donor strands needed for genome editing. In bacteria, the resulting editing tool built by pairing modified retrons with single‑stranded DNA–binding and annealing proteins is known as a recombitron. Until now, however, functional recombitrons existed only in E. coli.

To test whether the architecture could travel, the team designed a panel of 10 retron-based editing systems and partnered with other labs specializing in diverse bacterial species. “We designed all the molecular parts at Gladstone, then sent them to the collaborators, where they ran the experiment in their labs,” said first author Alejandro González‑Delgado, PhD. Samples were then returned to Gladstone for centralized analysis.

The results show broad functionality. The recombitrons worked in all 15 species tested, including clinically relevant pathogens such as Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as fast‑growing biotechnology strains like Vibrio natriegens and Pseudomonas putida. Editing efficiencies varied widely—from fractions of a percent to more than 90%—but the team demonstrated that modifying retron structure or other system components could boost performance in lower‑efficiency hosts.

“Each retron worked differently in different bacteria,” González‑Delgado noted. “This reinforces why it’s important to have lots of different retrons, so scientists can choose the ones best suited to their favorite bacterial species.”

The study provides a roadmap for expanding genome editing into species that have historically been difficult to engineer. Researchers studying microbial pathogenesis, gut ecology, or industrial bioproduction can now match retron systems to their organism of interest.

“My lab builds molecular technology, and we want these technologies to be used as broadly as possible to uncover new biology and intervene in disease,” Shipman said. “We hope it will continue to spread from here.”

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Headquartered in Jersey City, NJ, Organon was spun out of Merck in 2021 and has since then grown its portfolio to more than 70 women’s health and general medicines products, including biosimilars, that have been commercialized in the U.S. and some 140 countries worldwide. In addition to the U.S., Organon’s largest markets include Brazil, Canada, China, and the countries of the European Union. Organon said it has six manufacturing facilities across the EU and emerging markets.

Sun Pharma said the combined company created by the deal will have annual revenue of $12.4 billion, a figure the company said would propel it into a top 25 global pharma—though the company was ranked No. 14 in GEN’s most recent A-List of Top 25 Biotech Companies Heading Into 2026, compiled last December, based on its market capitalization (share price times the number of outstanding shares) of INR 4.31 trillion ($50.8 billion).

Sun Pharma said Organon’s portfolio was similar to its own, and that the acquisition of Organon was aligned with its strategies of growing its Innovative Medicines business (to a 27% revenue share) and expanding into biosimilars as a Top 10 global company.

The combined company, Sun Pharma and Organon said, would be top three in global women’s health, creating a commercial platform for future growth; the seventh largest global biosimilar player; and a presence in 150 countries worldwide, with 18 large markets that would each generate more than $100 million in revenues.

“This transaction represents a significant opportunity for Sun Pharma to build on its vision of Reaching People and Touching Lives,” Sun Pharma executive chairman Dilip Shanghvi said in a statement. “Organon’s portfolio, capabilities, and global reach are highly complementary to our own, and we believe that bringing the two organizations together can create a stronger and more diversified platform. We have deep respect for Organon’s mission and look forward to building on its legacy while driving sustainable long‑term growth.”

Deal speculation

The deal ends two weeks of speculation that began with an April 10 report in the Indian news outlet The Economic Times stating that Sun Pharma had submitted a $12 billion all-cash offer for Organon. On Friday, the news outlet followed up with a report stating that Sun Pharma had submitted a revised $13 billion offer.

Investors appeared to support the deal, as Sun Pharma shares on India’s National Stock Exchange rose about 7% to INR 1,733.50 ($18.41) at the close of trading today.

Sun Pharma has agreed to acquire 100% of Organon’s issued and outstanding shares for cash. Sun said it planned to fund the acquisition through a combination of available cash resources and committed financing from banks.

“Together, we will become a partner of choice for acquiring and launching new products,” stated Kirti Ganorkar, managing director of Sun Pharma. “Our immediate priorities will be business continuity, disciplined integration, and responsible value creation. We see strong potential in leveraging Organon’s talent pool. In addition, there is a scope for synergies including significant revenue upside opportunities to be realized over the coming years.”

Those synergies were later quantified by Sun Pharma as approximately $350 million within two to four years of the deal’s completion.

Sun Pharma did say, however, that the acquisition of Organon will strengthen its generation of cash, with its earnings before interest, taxes, depreciation, and amortization (EBITDA) and cash flow set to nearly double, supporting future efforts to reduce the net debt/EBITDA of 2.3x resulting from the deal.

Sun Pharma finished the first nine months of its fiscal year ending March 31, 2026, with a net profit of INR 87.654 billion ($931.5 million) and EBITDA of INR 137.772 billion ($1.464 billion; up 19.2% from the year-ago period), on sales of INR 436.604 billion ($4.64 billion), up 11.3% year over year.

During its fiscal year ending March 31, 2025, Sun Pharma reported adjusted net profit (excluding one-time items) of INR 119.844 billion ($1.274 billion), up 19% from a year earlier, on sales of INR 520.412 billion (about $5.53 billion). Reported net profit for FY 2025 was INR 109.290 billion ($1.161 billion), vs. Rs. 95.764 billion ($1.017 billion) during FY 2024.

Organon finished last year with adjusted EBITDA of $1.9 billion on revenue of $6.2 billion. The company reported debt of $8.64 billion—down from the $9.5 billion in debt it reported when it separated from Merck—and a cash balance of $574 million.

Planned sale

In November, Organon announced plans to sell its JADA^® System, designed to control and treat abnormal postpartum uterine bleeding or hemorrhage, to Laborie Medical Technologies for up to $465 million—$440 million to be paid at closing, subject to adjustments, and up to $25 million tied to achieving 2026 revenue targets. Net proceeds from the divestiture will contribute to Organon’s cash balance as of March 31, 2026.

Organon will merge with a subsidiary of Sun Pharma, with Organon surviving the merger. The transaction is expected to close in early 2027 subject to customary conditions, including regulatory approvals and Organon stockholder approval.

The boards of both Sun Pharma and Organon have approved the deal.

“Following a comprehensive review of strategic alternatives, our Board determined that this all‑cash transaction offers compelling and immediate value to Organon stockholders,” stated Carrie Cox, executive chair of Organon. “We believe Sun Pharma is well positioned to support Organon’s businesses, employees, and patients globally, and to further advance our commitment to delivering impactful medicines and solutions.”

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Using this self-organized pencil beam, the team captured 3D images of the human blood-brain barrier 25 times faster than the gold-standard method, while maintaining comparable resolution, according to the scientists.

By showing individual cells absorbing drugs in real-time, this technology could help scientists test whether new drugs for neurodegenerative disease like Alzheimer’s or ALS reach their targets in the brain, with greater speed and resolution, they add.

“The common belief in the field is that if you crank up the power in this type of laser, the light will inevitably become chaotic. But we proved that this is not the case. We followed the evidence, embraced the uncertainty, and found a way to let the light organize itself into a novel solution for bioimaging,” says Sixian You, PhD, assistant professor in the MIT department of electrical engineering and computer science (EECS), a member of the research laboratory for electronics.

You is senior author of a paper “Self-localized ultrafast pencil beam for volumetric multiphoton imaging” on this imaging technique in Nature Medicine.

A better beam

When the researchers performed characterization experiments of this pencil beam, it was more stable and high-resolution than many similar beams. Other beams often suffer from “sidelobes,”  blurry halos of light that can distort images.

Their beam was more pristine and tightly focused, according to You. Building on those experiments, the researchers demonstrated the use of this pencil-beam in biomedical imaging of the human blood-brain barrier.

Scientists and clinicians often want to see how drugs flow inside the vasculature of the blood-brain barrier and whether they reach their targets within the brain. But with standard optical settings, the best one can do is capture one 2D section of the vasculature at a time, and then repeat the process multiple times to generate a fuller image, You explains.

Using this new technique, the researchers created an ultrafast, high-precision pencil beam that enabled them to dynamically track how cells absorb proteins in real-time.

“The pharmaceutical industry is especially interested in using human-based models to screen for drugs that effectively cross the barrier, as animal models often fail to predict what happens in humans. That this new method doesn’t require the cells to have a fluorescent tag is a game-changer,” notes Roger Kamm, PhD, the Cecil and Ida Green Distinguished Professor of Biological Science and Mechanical Engineering.

“For the first time, we can now visualize the time-dependent entry of drugs into the brain and even identify the rate at which specific cell types internalize the drug.”

“Importantly, however, this approach is not limited to the blood-brain barrier but enables time-resolved tracking of diverse compounds and molecular targets across engineered tissue models, providing a powerful tool for biological engineering,” points out postdoctoral fellow Sarah Spitz, PhD.

The team reports that it captured cellular-level 3D images that were higher quality than with other methods, and generated these images about 25 times faster.

“Usually, you have a tradeoff between image resolution and depth of focus—you can only probe so far at a time. But with our method, we can overcome this tradeoff by creating a pencil-beam with both high resolution and a large depth of focus,” You says.

In the future, the researchers want to better understand the fundamental physics of the pencil-beam and the mechanisms behind its self-organization. They also plan to apply the technique to other scenarios, such as imaging neurons in the brain, and work toward commercializing the technology.

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Senescent cells walk a tightrope, risking cell death with high levels of iron and other damaging agents, but compensating for this by overproducing a protective protein, GPX4, which staves off death. The team showed that targeting this defense mechanism removes the shield and could be used to treat diseases that are associated with senescence, including cancer. Tests showed that combining anticancer therapies with GPX4 inhibitors eliminated senescent tumor cells in models of melanoma, prostate and ovarian cancer. This approach, they say, could complement existing treatments to bring much-needed improvements for cancer patients.

Mariantonietta D’Ambrosio, PhD, a postdoctoral researcher at the LMS, is first author of the international research team’s published paper in nature cell biology, titled “Electrophilic compound screening identifies GPX4-dependent ferroptosis as a senescence vulnerability.”

Cancers grow as a result of unconstrained cell division. But within most tumors, there is a portion that does not divide at all: senescent cells. Chemotherapy often increases the proportion of senescent cells in a tumor as it aims to stem the rapid proliferation, the team explained. However, while these senescent cells don’t directly increase the size of a tumor, they can wreak havoc in their own way.

Senescent cells, which are also a defining feature of aging conditions such as fibrosis, influence neighboring cells by secreting molecules that increase proliferation, the spread of the cancer, and unwanted immune system activity. “Senescent cells drive aging and age-related pathologies, including cancer,” the team wrote. There is therefore an increasing interest in developing drugs that directly target and kill senescent cells, in cancer and beyond. “Consequently, senolytics, drugs that selectively kill senescent cells, have broad therapeutic appeal,” they continued. “Compounds that selectively kill senescent cells (senolytics) can treat different age-related pathologies.”

The study by D’Ambrosio and colleagues has identified a new approach to killing senescent cells in cancer.  “Senescence was considered for a long time to be positive, because senescent cells don’t proliferate, which is the core feature of cancer,” D’Ambrosio explained. “Normal chemotherapy induces senescence blocking the proliferation of cancer cells, so the tumor doesn’t get bigger. But with time you also see the negative side of the senescent cells, because they secrete a lot of factors that influence neighboring cells and induce even more proliferation, metastasis, and recruitment of bad parts of the immune system that will provoke even more aggressiveness in the tumor.  For this reason, we tried to find some drugs that were able to kill the senescent cells.”

The researchers cast a broad net in their search for new drugs that might kill senescent cells. Together with collaborators at the Department of Medicinal Chemistry at Imperial, they decided to examine covalent compounds, a class of inhibitors that can form a covalent bond with their target, which can result in the inhibition of proteins previously considered undruggable. The investigators introduced 10,000 different covalent compounds to both senescent cells and normal cells, looking for the ones that preferentially killed senescent cells and classing the drug as “senolytic,” or senescent-killing.

They narrowed their results down to just four promising compounds and found that three of them affected a particular protein, GPX4, which has a protective role in cells, helping stave off ferroptosis, a type of cell death associated with high levels of iron and destructive reactive oxygen species. To protect themselves against the high levels of iron and other ferroptosis-causing agents, senescent cells have high levels of GPX4. It is like proactively taking a painkiller so a person can keep running on an ankle. The damage and danger remains, but the immediate risks are bypassed. Removing the painkiller makes the pain unbearable.

“Senescent cells are primed for ferroptosis and upregulate GPX4 as a protective mechanism,” the team noted. Ferroptosis had only recently been revealed as a potential weakness of senescent cells. D’Ambrosio commented, “recent papers have shown this predisposition of senescent cells to ferroptosis, but it’s a new senescence vulnerability. That creates an opportunity for us to exploit. So now there is research to find senolytic drugs to kill cells through ferroptosis.”

The researchers found that blocking the activity of GPX4 removes the shield, making fatal ferroptosis unavoidable. The authors further commented, “We concentrated our studies on four chloroacetamides displaying senolytic activity in different models of senescence … GPX4 was a target of three of the four senolytic chloroacetamides. GPX4 is a glutathione peroxidase that prevents ferroptosis by reducing lipid peroxidation.”

The team tested their drugs with three different mouse models of cancer and saw improved outcomes as a result of senescent cell death in each case. Translating this to patients could be a huge asset to cancer treatments. “In mouse models we saw that these drugs reduced tumor size, and improved survival,” noted professor Jesus Gil, PhD, senior author and head of the senescence group at the LMS. “Now we need to see the effect on the immune system. Is the improvement also awakening the ‘good side’ of the immune system (T cells, natural killer cells) that helps to kill the tumor? … Once we know more, the next step is to understand which cancer cell types or specific patients might better respond to this treatment. For example, if a patient undergoing chemotherapy overexpressed GPX4 then you could use this approach in combination with existing drugs to improve efficacy.”

This approach offers a much-needed new perspective on cancer therapy, pinpointing senescent cells as an underexploited target. D’Ambrosio says it has potential to transform treatment. “Targeting senescence is a huge opportunity for cancer treatments, and ultimately it can play a supporting role in addition to chemotherapy and immunotherapy.”

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