Researchers at the U.S. National Institute of Standards and Technology (NIST) and EMD Millipore put forward the idea, arguing that twins could make drug distribution, which is also characterized by thousands of interactions, more resilient and efficient.

Lead author Perawit Charoenwut, a logistics researcher at NIST’s systems integration division, tells GEN, “A digital twin could be extremely helpful in all phases of the biopharmaceutical supply chain. Starting from demand planning triggered by global events such as pandemics, regional disease outbreaks, aging demographics, etc., through to being able to provide visibility on capacity requirements and limitations.”

In silico models could also provide solutions to disruption by identifying alternative supply options, such as distribution centers or regional inventories, in less time, Charoenwut says.

“Digital twins could also be helpful in evaluating different suppliers by running simulations on their potential performance, based on different demand scenarios versus their individual capacities and capabilities,” he continues.

Standards

In theory, digital twins are a good option for supply chain modeling and management. In practice, however, firms interested in the approach will need to overcome some technical challenges.

For example, one major hurdle is the lack of data standardization, according to study co-author Boonserm Kulvatunyou, PhD, a computer engineer at NIST. “Supply chain digital twins require data from across organizations and third-party sources,” he tells GEN. “The lack of industry standards creates challenges in obtaining all the necessary data.”

With this in mind, the NIST’s Industrial Ontology Foundry (IOF) is working with the National Innovation Institute for Manufacturing Biopharmaceuticals (NIIMBL) to develop open-source ontology and schema standards for connecting data.

Kulvatunyou says, “The aim is to provide a semantic foundation for connecting data and knowledge across the manufacturing and supply chain operations.

“Further work is being conducted to cover broader materials, processes, and quality data,” he says. “We would like to invite industry and academia to join this effort and benefit from these new standards.”

Industry interest

Biopharma firms interested in digital supply chains will also need to establish a solid data infrastructure, according to Charoenwut, who says companies should start small and pace themselves.

“We think that biopharma companies do believe that digital twins could make a significant difference in their supply chain efficiency and resiliency. Many of them are probably building prototypes and proofs-of-concept to demonstrate the value and potential benefits, but then soon realize the digital data foundation gaps that need to be addressed in parallel in order to fully adopt this technology.

“As digital twins can vary in detail and complexity, companies should strategize digital twin adoption by starting with lower-complexity cases based on available digital data and progressively moving up the scale to gain greater precision and new capabilities. In other words, the implementation of digital twins should be viewed as an evolution rather than a breakthrough,” he says.

The post Supply Chain Digital Twins: An Evolution, Not a Breakthrough appeared first on GEN - Genetic Engineering and Biotechnology News.

These nanoscale carriers are naturally designed for transport. They can survive digestion, move into circulation, and distribute cargo throughout the body, with studies suggesting they may even reach the brain during early development. Researchers have shown that these vesicles can influence central nervous system communication, particularly through interactions with microglia, which are crucial to the brain’s immune cells. The ability of milk exosomes to carry microRNAs and regulate epigenetic pathways, including DNA methyltransferase 1 (DNMT1), points to a sophisticated biological delivery system that the industry is now learning to harness.

That potential is especially compelling in drug manufacturing, where delivery often determines whether a therapy succeeds or fails. Traditional nanoparticles can trigger toxicity, instability, or poor absorption. Milk exosomes offer a more elegant alternative: they are biocompatible, naturally abundant, and scalable for pharmaceutical development.

Huiming Tu, MD, a researcher and clinician in the department of gastroenterology at the Affiliated Hospital of Jiangnan University in Wuxi, China, and his colleagues recently demonstrated this with ulcerative colitis. Their team developed an oral delivery platform called mEXOs@TOF, which loads the pan-JAK inhibitor tofacitinib into milk-derived exosomes. The resulting formulation showed strong pharmaceutical performance, including consistent particle size, high drug-loading efficiency, and strong stability during delivery.

More importantly, the therapy improved anti-inflammatory outcomes through multiple mechanisms. It lowered inflammatory mediators such as IL-6, IFN-γ, and nitric oxide, while increasing anti-inflammatory IL-10. It also reduced oxidative stress and suppressed activation of the JAK-STAT3 signaling pathway. In both laboratory and animal studies, the system delivered strong therapeutic benefits without detectable toxicity—an ideal benchmark for translational bioprocessing.

Cancer therapy is seeing similar innovation. Min Suk Shim, PhD, professor of nano-bioengineering at Incheon National University in the Republic of Korea, and colleagues focused on sonodynamic therapy, in which ultrasound activates a sensitizing drug to destroy tumors. Their challenge was improving intracellular delivery of chlorin e6 (Ce6), a common sonosensitizer.

The team engineered glutathione-responsive milk exosomes by incorporating a diselenide bond-bearing fatty amine derivative. This allowed the vesicles to remain stable during circulation but release Ce6 inside breast cancer cells, where glutathione concentrations are higher. Once ultrasound was applied, reactive oxygen species production increased dramatically, leading to significant cancer cell death in MCF-7 breast cancer models. The work shows how responsive bioprocess design can turn natural vesicles into precision-triggered therapeutics.

Meanwhile, scientists from Hong Kong and China have reviewed the broader landscape of milk exosomes in breast cancer treatment. Beyond acting as delivery vehicles for drugs like doxorubicin, paclitaxel, and 5-fluorouracil, milk exosomes may also have direct anti-tumor effects. They can promote apoptosis, interrupt the cell cycle, and regulate pathways such as NF-κB and STAT3. Combined with plant-derived compounds like curcumin and resveratrol, they form hybrid nanoparticles with enhanced therapeutic power.

For bioprocessing, the message is clear: milk exosomes are no longer a niche curiosity. They represent a scalable, safe, and highly adaptable platform for next-generation therapeutics—one that begins with biology’s oldest delivery system and may define medicine’s next one.

The post Milk Exosomes Transform Therapeutic Bioprocessing appeared first on GEN - Genetic Engineering and Biotechnology News.

Hagen Cramer, PhD, QurAlis’s CTO, thinks synthesizing oligonucleotides using enzymes could be more sustainable than traditional solid-phase synthesis methods, but challenges remain for the industry.

“Solid-phase synthesis is convenient—you can have everything automated, it’s fast, and can be used for [many] types of therapeutics,” he says. “However, because it’s a solid-phase synthesis, you have to wash away the external reagents with lots of solvents, and that’s why the mass intensity is high.”

By contrast, manufacturing RNA and DNA using a process that happens in nature and is aqueous-based uses fewer materials in the production of any given mass of product, notes Cramer. However, creating a wide selection of enzymes to manufacture multiple products remains a challenge for the industry.

“Enzymatic synthesis]was explored a long time ago, but it went away because people couldn’t figure out the challenges,” he points out. “But there’s now a lot more money in the industry as we have approved drugs and, hence, it’s now being reinvestigated.”

Other challenges include using enzymatic techniques for manufacturing above the 100-g scale and also speeding up these techniques to be comparable with solid-phase synthesis.

“With solid-phase synthesis, if you have a 20-mer oligonucleotide, you might have to take 80 chemical steps, and you can be efficient and complete all of that in a day, but—with an enzymatic approach—it’s going to take much longer and the development time is also large,” explains Cramer, adding that clinical-stage companies making smaller volumes may want to stick with solid-phase synthesis. But, he continues, commercial-stage companies producing large volumes of product may want to investigate enzymatic approaches as they become available.

“At a certain stage, if you’re working at commercial stage already, you can plan ahead and I think the industry will move toward these new approaches starting post-market,” he says.

The post Hopes Raised for More Sustainable Oligonucleotide Manufacturing appeared first on GEN - Genetic Engineering and Biotechnology News.

The Adaptive Agent-Oriented System Control (AAOSC) framework developed by a team from the Technical University of Denmark (DTU) and SiC Systems addresses that challenge through a decentralized control layer. In it, “specialized autonomous agent ‘hives’ [are] coordinating digital twin enabled manufacturing infrastructure and real-time communications protocols.” The latter lets biomanufacturers integrate models, make learning-based inferences, and control process systems.

Four AAOSC case studies were discussed in a recent paper by Seyed Soheil Mansouri, PhD, professor at DTU and co-founder and CSO of SiC Systems and Christopher J. Savoie, PhD, co-founder and CEO of SiC Systems, and inventor of the agentic AI technology behind Siri. Those case studies “demonstrate AAOSO’s prowess [in] reducing deviating durations, averting shutdowns in severe fault scenarios, and boosting efficiency through virtual quantum and classical sensing and decentralized reasoning, all while aligning with regulatory imperatives…”

Despite its capabilities in monitoring process, identifying discrepancies, and recommending solutions, agentic AI “is not yet fully ready for complete, independent control in biopharmaceutical manufacturing,” Mansouri tells GEN. “Any AI that directly affects medicine quality still needs strong human oversight and full approval. We are getting closer, but full integration requires official [regulatory] clearance.”

The AAOSC framework that Mansouri and colleagues built may be unique in the industry. It isn’t all-knowing and “God-like,” he points out. Instead, “our methods are grounded in physics, chemistry, and biology within an agent ‘hive’—an orchestration of rule-based, mathematically informed agents. So, AAOSC is, foundationally, a different philosophy of building AI [in which] humans are in control.”

First, run in shadow mode

To introduce agentic AI, Mansouri advises starting gradually. “Run the AI alongside your current control systems in shadow mode—it watches everything and gives recommendations, but doesn’t make any actual changes without human oversight. This lets the teams learn how it works without any risks to production. Once confident, you can slowly expand its role while always keeping humans in final control.”

Both the FDA and EMA require systems that are fixed rather than continuously learning, he points out, and that can complicate adoption. To minimize the potential for regulatory issues that may arise by integrating AI into manufacturing processes, “work closely with your quality and regulatory teams from the beginning.

“Always maintain clear human responsibility, so no one is left wondering who is accountable if something goes wrong. Strong cybersecurity is essential,” Mansouri adds, “because these AI agents connect and talk to each other.” Therefore, “Start small, test thoroughly, and talk to regulators early.”

The post Adaptive, Agent-Oriented Control for Biomanufacturing Systems appeared first on GEN - Genetic Engineering and Biotechnology News.

The researchers examined approximately 5.5 million neurons in more than 300 individual mice using single-cell sequencing and spatial transcriptomics. Results showed that neurons are organized into tight, overlapping, horizontal stripes from the top to the bottom of the nose based on the type of smell receptor expressed. This highly organized receptor map was consistent across mouse models and mirrored the organization of smell maps in the brain. Similar maps have been observed in vision, hearing, and touch.

Notably, the olfactory map was informed by a gradient of retinoic acid in the nose, which allowed each neuron to express the correct type of smell receptor based on its spatial location.  

“Our results bring order to a system that was previously thought to lack order, which changes conceptually how we think this works,” said Sandeep (Robert) Datta, PhD, professor of neurobiology at HMS and senior author and corresponding author of the study. “We show that development can achieve this feat of organizing a thousand different smell receptors into an incredibly precise map that’s consistent across animals.” 

The authors also found that the receptor map in the nose matches up with smell maps in the olfactory bulb of the brain, shedding insight into how information moves from the nose to the brain. 

While sensory maps that describe how receptors in the eye, ear, and skin are organized to capture and interpret auditory, visual, and touch information, mapping olfactory receptors has been a longstanding challenge due to high receptor diversity. As an example, mice have approximately 20 million olfactory neurons that express more than a thousand types of smell receptors, compared with only three main types of visual receptors for color vision. Each type of smell receptor detects a unique subset of odor molecules. 

The team is also studying smell receptors in human tissue to understand to what degree the smell map is consistent across species to inform treatments, such as stem cell therapies and loss of smell and its consequences, such as an increased risk of depression. 

“Smell has a really profound and pervasive effect on human health, so restoring it is not just for pleasure and safety but also for psychological well-being,” Datta said. “Without understanding this map, we’re doomed to fail in developing new treatments.” 

The post Loss of Smell Therapies Informed by Olfactory Receptor Spatial Mapping appeared first on GEN - Genetic Engineering and Biotechnology News.

The collaboration brings together the circVec platform and TraffikGene’s peptide amphiphile carrier system. The combination of these complementary technologies is designed to enable high-throughput screening of circVec delivery with enhanced tissue targeting. The aim is to identify optimized formulations capable of prolonged, efficient, and targeted delivery of non-viral circVec vectors into specific cell and tissue types.

“Combining TraffikGene’s carrier discovery capabilities with Circio’s innovative circular RNA scaffolds opens a compelling new avenue for the development of next-generation nucleic acid medicines,” said Javier Montenegro, PhD, principal investigator of the TraffikGene project at USC.

The collaboration will involve three stages: initial screening of peptide carriers combined with non-viral circVec vectors in vitro, physicochemical optimization of lead formulations, and in vivo evaluation in mouse models to assess expression kinetics, biodistribution, and delivery efficacy.

“Cutting edge delivery technologies are essential to reach new tissues in an efficient and safe manner,” added Thomas B Hansen, PhD, CTO of Circio. “This collaboration is an excellent opportunity to evaluate whether TraffikGene’s non-viral carriers can unlock the full potential of Circio’s circVec platform. In addition, it will allow us to evaluate circular RNA expression dynamics and tissue-specific performance in more detail, which are key research areas to identify new therapeutic applications for the circVec platform.”

The post Circio Partners with TraffikGene Project to Advance Non-Viral circVec Delivery appeared first on GEN - Genetic Engineering and Biotechnology News.

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.”

The post Hepatocyte Detargeting Improves mRNA Vaccine Immunity in Lymphoma Model appeared first on GEN - Genetic Engineering and Biotechnology News.

“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.”

The post Method Identifies Cellular Makeup of Microenvironments Favoring Tumor Metastasis appeared first on GEN - Genetic Engineering and Biotechnology News.

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.

The post WHO Designates Network of Regional Biomanufacturing Training Centers appeared first on GEN - Genetic Engineering and Biotechnology News.

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.”

The post ‘Type’ Casting: Flagship-Founded Serif Modifying DNA into New Therapy Class appeared first on GEN - Genetic Engineering and Biotechnology News.