Listed below are links to the GEN stories referenced in this episode of Touching Base:

Fulcrum Halts Development of SCD Candidate Pociredir, Sets Strategic Review
By Alex Philippidis and Kevin Davies, PhD, GEN Edge, June 2, 2026

Biohub Releases Protein Biology World Model to Address Disease
By Fay Lin, PhD, GEN Edge, May 27, 2026

Cross-Reactive T Cells Could Point to Broad Vaccines or Treatments for Measles, Nipah Virus
GEN, June 2, 2026

Experimental Adjuvant Could Strengthen Mucosal Immunity with Injectable Polio Vaccines 
GEN, June 4, 2026

Touching Base Podcast
Hosted by Corinna Singleman, PhD

Produced with support from:

The post A Billion-Dollar Deal, Trial Trouble, Biohub Updates, and Vaccine Research News appeared first on GEN - Genetic Engineering and Biotechnology News.

One of medicine’s greatest challenges is ensuring that treatments reach the precise area of the body where they are needed. While recent scientific breakthroughs have identified numerous targets for neurological conditions, the difficulty of effectively transporting these treatments across the blood-brain barrier and into the central nervous system (CNS) remains a primary challenge for global health.

According to the World Health Organization’s Global Status Report on Neurology, over 40% of the global population is living with CNS diseases, making them a leading global cause of ill health and disability.

Directly addressing critical gaps in healthcare means these innovations have the potential to improve patient outcomes while creating clinical and commercial opportunities for biotech and pharma companies. Developing new solutions could unlock access for rare neurological disorders and expand treatment to large or underserved patient populations, including those with diseases such as Alzheimer’s, Parkinson’s, and various brain cancers.

The first phase of the partnership will see an in-depth review of the current medicines landscape conducted to identify opportunities for innovation. This information will then be used to identify systemic gaps in brain-entry technologies. The long-term ambition is for novel approaches that meet the investment criteria of the partners to be spun out into new ventures focused on high-impact solutions and to provide them with pre-seed funding.

A core part of DSV’s approach involves building future founding teams to form new companies that will address challenges across multiple sectors. Future founders will work on opportunities that have been pre-scoped by DSV, de-risking the standard founder proposition.

By combining DSV’s venture-building model with MDC’s drug discovery expertise and infrastructure, the partnership will aim to develop new approaches to ensure life-changing medicines reach the brain, according to Adam Tomassi-Russell, senior director, DSV.

“The blood-brain barrier remains one of the most complex issues in modern medicine and with over 40% of the world’s population facing neurological conditions, it’s imperative that we find an optimal solution to this problem,” said Tomassi-Russell. “By pooling our venture-creation expertise with MDC’s discovery capabilities, we can offer the right founders a frictionless environment in which to tackle the CNS delivery gap. If we can solve the ‘how’ of brain entry more effectively, we can unlock a new frontier of CNS therapeutics and address the huge unmet need in these diseases.”

“At MDC, we are committed to transforming bold ideas into better treatments,” added Nicola Heron, chief strategy officer, MDC. “This collaboration presents an opportunity to discover new technologies that could have a significant impact on patients and society. Through this partnership, we will strengthen the ecosystem for CNS innovation in the U.K. and beyond, enabling more medicines to reach patients faster.”

The post Brain-Targeted Drug Discovery Barriers Drive Deep Science Ventures and Medicines Discovery Catapult Deal appeared first on GEN - Genetic Engineering and Biotechnology News.

The paper is titled “Single-cell mapping of regulatory DNA-protein interactions,” and was published recently in Cell.

“D&D-seq couples an antibody-binding nanobody to a cytosine base editor, a combination that enables detection of weak or transient factor binding through targeted cytosine-to-uracil [C→U] editing at protein-bound genomic sites,” the authors wrote. Those edits become a molecular breadcrumb trail, revealing where regulatory proteins have interacted with the genome.

This approach directly addresses a long‑standing gap in the field. Traditional methods for mapping transcription factor binding, such as ChIP‑seq or CUT&RUN, “cannot be easily incorporated into high-throughput single-cell workflows, limiting applications to bulk analysis or to single-cell profiling of only the strongest interacting chromatin factors. Single-cell profiling of TF binding in primary samples has been mainly restricted to inferential approaches based on expression levels of downstream TF target genes or through motif analysis of assay for transposase-accessible chromatin using sequencing (ATAC-seq) peaks, but identification of specific TF-binding sites requires more direct methods,” according to the authors.

The team demonstrated that D&D‑seq can map binding sites for transcription factors and other regulatory proteins, like chromatin remodeling proteins, across multiple cell types and conditions. One application involved profiling CTCF binding in primary T cells carrying an IDH2 mutation commonly found in leukemia. Because D&D‑seq operates at single‑cell resolution, it exposes heterogeneity in regulatory wiring that is often masked in population‑level assays.

Crucially, the method is platform‑agnostic. The authors showed that D&D‑seq can be integrated into standard single‑cell multiomics workflows, including ATAC‑seq, scATAC‑seq, and whole‑genome sequencing. That compatibility allows researchers to pair DNA–protein interaction maps with chromatin accessibility, gene expression, and genomic variation—all within the same cell.

As transcription factors and other regulatory proteins increasingly emerge as therapeutic targets, tools that reveal how these factors behave in patient‑derived cells will be essential. D&D‑seq offers a way to monitor how mutations, drugs, or engineered perturbations reshape regulatory landscapes at single‑cell resolution.

“We’re entering an era of medicine in which transcription factors and other gene-activity regulators will increasingly be therapeutic targets,” said Dan Landau, MD, PhD, the Bibliowicz Family professor of medicine and a member of the Sandra and Edward Meyer Cancer Center and the Englander Institute for Precision Medicine at Weill Cornell, who is also an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. “This kind of technology should have an important role in developing and evaluating such therapies.”

Although the method is still evolving, its conceptual elegance and technical flexibility have already sparked broad interest. By turning DNA into a recording surface for protein activity, D&D‑seq opens a new window into the “regulome”—one that captures the subtle, transient interactions that drive cellular identity and disease.

The post D&D‑seq Uses Base Editing to Map DNA–Protein Interactions in Single Cells appeared first on GEN - Genetic Engineering and Biotechnology News.

“People have talked about viral xenophagy before as a sort of concept, but if you look in literature, there aren’t any good examples where people have shown this operating to potently block infection,” said James. “In our single study, we’ve gone from the discovery of something completely unknown [ADX], all the way through molecular mechanism, its function in cells into animals, and demonstrated physiological importance.”

The discovery of the ADX pathway may have potential future medical implications. While far more study is needed, the research points to the feasibility that antibody or small molecule therapeutics could be used to treat infections by marking pathogens in the blood so TRIM21 can recognize and jumpstart ADX once they enter cells.

James, Rhinesmith, and colleagues reported on their findings in Molecular Cell, in a paper titled “TRIM21 induces selective autophagy of viruses and bacteria,” stating, “We propose that TRIM21 evolved through competition with pathogens to induce autophagy of diverse and complex substrates, potentially explaining its versatility for targeted protein degradation.”

Typically, the body will respond to an infection by creating antibodies that latch onto the invaders in the blood to alert immune cells, such as white blood cells, to destroy them. Sometimes, those antibody-bound pathogens evade the immune cells and infect healthy cells. This is where antibody-directed xenophagy becomes involved.

Using CRISPR-Cas9 and quantitative imaging, the team determined that once an antibody-labeled pathogen enters a cell, ADX begins with the specialized protein TRIM21, which flags the pathogen with a ubiquitin marker that signals to the cell that it has been invaded.

TRIM21 is an intracellular E3 ubiquitin ligase protein that binds to antibodies and catalyzes ubiquitination. Prior work by James’s group had found that TRIM protects against viral infection by binding to antibody-coated viruses in the cell, triggering ubiquitination and viral degradation.

“Recently, we and others have shown that the degradative adaptability of TRIM21 extends to a wide range of additional substrates beyond viral capsid proteins,” the team further pointed out. “TRIM21 is an exceptionally versatile ubiquitin ligase that can be directed by antibodies to target oligomeric protein scaffolds, viral capsids, and proteopathic aggregates for intracellular degradation.”

However, the mechanism used by cells to degrade the tagged viruses wasn’t known. “… how such a large and complex substrate is quickly and efficiently degraded remains unclear.”

Rhinesmith, a post-doc in James’s group, conducted a genome-wide CRISPR-Cas9 knockout screen, individually removing every gene across the human genome and testing how its deletion impacted TRIM21-triggered degradation of viruses. The results were striking, revealing a previously undescribed process by which TRIM21 is able to trigger autophagy of cell-invading viruses.

Autophagy is a conserved cellular process through which damaged or toxic cellular components are delivered to specialist acidic organelles to be degraded and recycled. While this process plays a key role in maintaining cellular health, its ability to protect against invading viral pathogens hasn’t been well studied.

Staff scientist Anna Albecka developed a high-fidelity confocal microscopy platform that allowed the team to visualize previously unidentified events in the TRIM21 restriction mechanism. The team observed binding of TRIM21 to antibody-coated viruses inside cells, in real time. The microscopy results showed that after TRIM21 ubiquitinates the invading virus complex, ubiquitin stimulates the assembly of autophagy components around viruses, including LC3, a marker for membranous compartments called autophagosomes.

Working with Claudia Puri and David C. Rubinsztein at the U.K. Dementia Research Institute, Cambridge, the team used super-resolution microscopy to visualize the assembly of these autophagosome membranes around individual viral particles coated in antibodies and TRIM21. Together, these observations revealed the stepwise process by which incoming virions are incarcerated inside sealed, LC3-positive autophagosomes.

Albecka was further able to show that these virus-containing autophagosomes are ultimately delivered to acidic lysosomes, resulting in the degradation of each virus into harmless peptides and nucleotides. Significantly, the study suggests that antiviral autophagy is a highly effective strategy deployed by cells to protect themselves from infection, and provides new tools for investigating this process.

Inspired by the ability of TRIM21 to activate by clustering around clients of very different architectures, the team next sought to understand whether it could also intercept a completely different type of pathogen: bacteria. The team used antibodies and a novel live cell microscopy method to track bacterial growth inside mouse cells. They observed the same ADX pathway that intercepts viral infection also potently restricts the growth of intracellular Salmonella. This discovery is significant because it explains how TRIM21 is able to intercept and trigger the degradation of invading pathogens of many complex structures and diverse lineages. “Importantly, our data explain how TRIM21 can degrade large and highly complex substrates,” the authors stated. “The need to intercept and destroy phylogenetically and structurally diverse pathogens may have driven the evolution of TRIM21’s very broad substrate versatility.”

By leveraging the intrinsic flexibility of the autophagy pathway, ADX can adapt to and degrade a variety of large and difficult targets. The findings indicate that the cell does not require a bespoke defense strategy for every individual pathogen. Instead, it employs a universal strategy, reliant on TRIM21, to redirect the cell’s existing autophagy machinery to any harmful material tagged with antibodies. This adaptability makes ADX clinically important for human immunity and, excitingly, a potential target for therapeutic enhancement.

“TRIM21 is unique because it uses the antibodies attached to the invading virus or bacteria to alert the cell,” said James. Rhinesmith added, “We show in the paper that on top of non-enveloped viruses, it’s also able to target bacteria along the same pathway. It seems that you trigger ubiquitination of whatever pathogen has antibodies around it through TRIM21, and this is the key step that leads to autophagy of the bacteria or the virus.”

This ability for cells to fight back from the inside doesn’t appear limited to specific cells within our body. The research team tested for the presence and action of TRIM21 against adenovirus in a range of human cell lines, as well as living mouse models in the case of Salmonella. These experiments indicated that ADX-mediated immunity is likely ubiquitous throughout the human body. “TRIM21 is expressed from what we call an ‘interferon-stimulated gene,’ which means that it is upregulated during infection, so your body makes it all the time, everywhere,” said James. “And the reason why you make it everywhere is so that you can potentially protect any cell or tissue.”

Though ADX may sound like a backup for our immune system for when pathogens evade our first lines of defense, the authors noted that this could be an equally important primary mode of protective immunity. “Our data shows that without TRIM21, a significant component of protective immunity in vivo against viruses is lost. In practice, immunity works because we’ve got different mechanisms operating together,” James said.

TRIM21 is the first intracellular protein discovered to stimulate ADX immunity, but there may be others that have equally broad or specific pathogen targets. Part of the research team’s next steps is determining the existence of other ADX-stimulating proteins and what limitations there may be to TRIM21’s function.

The post Novel Intracellular Pathway Identified That Protects Against Viral and Bacterial Infection appeared first on GEN - Genetic Engineering and Biotechnology News.

From the CEOs of the major labs to AI skeptics and safety organizations to luminaries in the life sciences, public health, and national security, there is wide agreement that we need stronger screening guardrails. The letter calls on U.S. lawmakers to codify mandatory nucleic acid synthesis screening, including recordkeeping, in order to combat the development of biological weapons at the scale of AI. The open letter reads as follows:

As life sciences researchers, builders of AI and biotechnology, and experts with a wide range of views on how to approach AI policy, we call on legislators to make screening of orders for synthetic nucleic acids—and the equipment needed to make them—mandatory. 

While the issue is not new, the pace of progress in artificial intelligence is. AI systems now outperform PhD-level virologists on questions about highly technical laboratory procedures in their own domains of expertise. The evidence about what this means for present-day biosecurity threats is genuinely mixed, but the trend is hard to dispute. AI systems are improving rapidly, and alongside incredible benefits to science and medicine, there is a real possibility that the knowledge barriers which have historically prevented bad actors from obtaining biological weapons will meaningfully erode.

Support for screening does not depend on any particular view of AI; the biosecurity case has been recognized by scientists and governments for decades. Screening is also one of the best understood and least disruptive biosecurity measures available. It asks providers of synthesized DNA and manufacturers of synthesis machines to check synthesis requests for sequences of concern and to verify customer legitimacy before shipping orders. Providers should also record synthesis orders and sequence data to support legitimate biosecurity investigations, so that any threat that might evade initial screening can be traced back to its source—including when individual sequences would not raise concern in isolation. Awareness of traceability itself deters misuse.

Many of the largest and most responsible providers in the industry already screen and record orders voluntarily because it is well understood that they have an important role to play in maintaining public trust in and mitigating potential misuse of this important technology.

For these reasons, the undersigned support mandatory nucleic acid synthesis screening, including recordkeeping, in the United States.

Given the pace at which the underlying technology is changing, we believe the need is urgent. Congress should act this session, and we applaud the legislative efforts currently underway. To ensure a consistent national standard rather than a patchwork of conflicting laws, states should also consider implementing requirements based on existing federal and industry guidelines.

This is a rare moment of agreement across stakeholders who are often at odds. We hope policymakers will meet it with decisive action.

You can find the full list of signatories and the letter here. Two organizations are the primary organizers of the letter: the Institute for Progress (IFP) and the Foundation for American Innovation (FAI). The best email contact regarding the open letter is letter@screendna.org.

The post Open Letter: In Support of Mandatory Nucleic Acid Synthesis Screening and Recordkeeping appeared first on GEN - Genetic Engineering and Biotechnology News.

Now according to data from an Massachusetts Institute of Technology-led study, it may be possible to modify the injectable vaccine so that it can also promote a mucosal immune response. This way, the vaccine could support polio eradication efforts without the risks of the oral polio vaccine. Details are published in a new Science Advances paper titled “Am80-Lipid nanoparticles serve as an enteric mucosal adjuvant 3 following parenteral immunization with inactivated polio vaccine.”

In comments that shed some light on the thinking behind the work, Ana Jaklenec, PhD, a principal investigator in MIT’s Koch Institute for Integrative Cancer Research, stated that while “people who are vaccinated with the injectable vaccine are not getting sick” they may be helping spread the highly contagious virus. “Mucosal immunity could help lower that shedding and ideally eliminate it,” she said. 

Her team’s version of the vaccine comprises an injectable, inactivated polio vaccine delivered with a nanoparticle-based adjuvant that helps steer immune cells to the mucosal lining of the intestine. Digging into the details, Jaklenec and her team worked with a group at Harvard Medical School who have shown previously that using a derivative of vitamin A as a vaccine adjuvant can help stimulate immune cells to go into the GI tract. 

Though the adjuvant, known as Am80, generates a strong response, one challenge is that it needs to be injected for several days in a row, which is not feasible for most vaccine campaigns. To eliminate the need for repeated vaccinations, the scientists used a lipid nanoparticle (LNP) as a delivery vehicle that releases the adjuvant slowly over several days.

Armed with the updated vaccine, the scientists moved on to testing it in rats. For their tests, the scientists injected the standard inactivated polio vaccine along with a separate injection of Am80 encapsulated in LNPs. They also delivered boosters to the rats at four and eight weeks. 

Following injection, LNPs accumulate in the lymph nodes where they interact with B and T cells that are also exposed to the polio vaccine. The interaction stimulates the cells to produce two surface proteins that direct them to the GI tract. Additionally, the B cells produce IgA antibodies, which protect body surfaces from infection by coating the mucosal membranes. Lastly the rats produce IgG antibodies in the bloodstream, which are similar to the antibodies produced in response to the standard injected polio vaccine. 

Overall, in the rats, they found that administering the vaccine and adjuvant produced a two-fold increase in the type of antibodies needed for mucosal immunity compared to the inactivated vaccine alone. Essentially, “by adding Am80 to lipid nanoparticle as an adjuvant, we are combining the safety of IPV with an adjuvant that can produce the mucosal immunity that normally you can only get with OPV,” said Behnaz Eshaghi, PhD, a postdoctoral student at MIT and lead author of the paper. 

For their next steps, the scientists plan to test the improved vaccine in other large animal models where they will inject the vaccine and adjuvant mixed together. More broadly, Am80 and similar adjuvants could help scientists design improved vaccines for other pathogens that infect the GI tract or for diseases that infect the lungs or reproductive tract. 

The post Experimental Adjuvant Could Strengthen Mucosal Immunity with Injectable Polio Vaccines appeared first on GEN - Genetic Engineering and Biotechnology News.

Officials at Stipple Bio say the company is leveraging its Pointillist Platform to identify tumor-specific cell surface epitopes, which can enable the development of high therapeutic index medicines designed to avoid on-target/off-tumor toxicity. Under the agreement, Stipple Bio will gain target-specific access to Lonza’s ADC technology platform to design potential first-in-class and best-in-class ADC products, including STP-100.

This collaboration combines Stipple Bio’s epitope discovery capabilities with Lonza’s GlycoConnect antibody conjugation technology, HydraSpace^® polar spacer technology, and a toxSYN^® linker payload. In addition, Lonza is eligible to receive upfront, clinical, regulatory and commercial milestone payments, plus royalties on net sales of resulting products. Lonza is responsible for manufacturing components that are related to its proprietary technologies, and Stipple Bio is responsible for the R&D, manufacturing, and commercialization of the ADCs.

“We value the opportunity to work with Stipple Bio to support their innovative epitope discovery approach with our advanced ADC technologies,” said Jan Vertommen, head of commercial development, advanced synthesis, Lonza. “By combining their science with Lonza’s established bioconjugation platforms and efficient, scalable manufacturing capabilities, we aim to help Stipple Bio progress more precise and effective ADC programs with confidence and speed.”

“ADCs have become a core pillar of cancer treatment, and as the field advances, increasingly sophisticated design is translating into stronger efficacy and reduced off-target effects,” added Jeff Landau, CEO, Stipple Bio. “We are pleased to be partnering with Lonza and believe that their clinically validated platform will be instrumental in enabling us to translate that design sophistication into effective and better tolerated therapies.”

The post Stipple Bio and Lonza Agree to Focus on Advancing Oncology ADC Therapies appeared first on GEN - Genetic Engineering and Biotechnology News.

Headed by Makedonka Mitreva, PhD, the Gordon R. Miller Professor in the John T. Milliken Department of Medicine’s Division of Infectious Diseases at WashU Medicine, the investigators report what they say is the first successful genetic modification of the human hookworm, which they engineered to produce an antibody that neutralizes tetrodotoxin (TTX), a deadly neurotoxin produced by pufferfish and other marine animals. The team’s preclinical study demonstrated that the modified hookworms colonized an animal host, and secreted the antitoxin into the host bloodstream, partially inactivating the toxin. They say the findings demonstrate that this drug production and delivery approach could potentially offer a long-term solution for multiple indications, including continuous treatment for chronic conditions, or for exposure to toxins in remote settings.

“The hookworm has spent millions of years perfecting how to assure long-term survival inside a human host and how to get molecules out of its body and into ours,” said Mitreva. “We asked: What if we could add one more molecule to the roughly 1,000 things the worm already secretes, something therapeutically useful to people? This study shows that’s not just a concept. It works.”

Mitreva and colleagues reported on their study in Nature Communications, in a paper titled “Transgenic hookworm secretes anti-tetrodotoxin human single chain antibody.” In their paper the team concluded that their achievement, “… represents a critical step towards the development of a transgenic human hookworm pharmaceutical biofactory platform with the potential to continuously, safely, and effectively deliver biologics in situ within patients.”

“Hookworms have evolved to survive for years within the human host while minimally disrupting host homeostasis, and controlled human infections with hookworms are safe and well-tolerated in clinical settings, bolstering their potential for utility as pharmaceutical biofactories,” the authors wrote.

Hookworms have already been studied as treatments for inflammatory bowel diseases such as ulcerative colitis, based on evidence that the anti-inflammatory molecules the worms secrete can dampen the immune responses that drive those conditions. Mitreva’s team set out to build on that foundation by engineering the worm to secrete a therapeutic of the researchers’ choosing, rather than relying solely on what the parasite produces naturally.

The appeal of hookworms as a long-term drug production and delivery platform stems from a quirk of their biology. When a person is infected with a controlled number of hookworm larvae, which can be administered orally as a pill or through the skin like a lotion, the worms migrate to the small intestine and take up residence, often for years. Because they cannot multiply inside the host, the number of worms stays fixed, and the infection remains controlled. If the infection ever needs to be cleared, a single dose of an oral anti-parasitic drug eliminates the hookworms within 24 hours.

To adapt hookworms for therapeutic use, Mitreva and her team drew on more than two decades of hookworm genomics research conducted at WashU Medicine. This depth of data helped them understand the organism’s biology from the cellular to the genetic level, allowing them to locate a viable site in the genome to insert the new gene carrying instructions for making the new antitoxin. The antibody selected for the team’s reported proof-of-concept study neutralizes tetrodotoxin, a paralyzing and potentially lethal toxin with no antidote.

The project presented significant technical hurdles: gene-editing tools that work in other organisms had not been adapted for hookworms, and no one had previously achieved stable genetic modification in the species. Critically, they had to ensure the insertion wouldn’t disrupt surrounding gene activity and would prompt the worm to secrete the antitoxin out into the host.

The team reported that blood collected from hamsters infected with the genetically modified hookworms partially neutralized tetrodotoxin, whereas blood from animals infected with unmodified worms had no neutralizing capability. Mitreva noted that the level of neutralization achieved in this initial study, while significant, likely represents only a fraction of what the platform can ultimately deliver. They wrote in summary “Here, we report on methodological, technical, and conceptual advances, demonstrating successful bioengineering of a human hookworm, Ancylostoma ceylanicum, to produce and secrete a human single-chain antibody, s16-HuScFv, that neutralizes tetrodotoxin (TTX).”

Several components of what she calls a “configurable chassis” are still being optimized to increase the amount of therapeutic protein produced and secreted. Because the worm resides in the gut and a substantial portion of what it secretes remains there, rather than entering the bloodstream, the researchers expect that concentrations of therapeutic molecules in the intestine may be substantially higher than what was detected in circulation in this study, making the platform suitable for gut-directed therapies.

In their paper the team wrote, “Building on the foundation that experimental human hookworm infection has been shown to be safe and well tolerated, here we present technological, methodological, and conceptual advances that have enabled the establishment of a genetically modified and tractable model system that can produce and deliver biologics … Taken together, this transgenic human hookworm platform highlights a promising approach in biotechnology that has the potential to significantly advance how we conceptualize disease treatment and prevention. Technologically, it also constitutes a notable advance in functional genomics for hookworms and helminths more broadly.”

Mitreva added, “What we demonstrated here is that the concept works end to end—you can insert a gene, the worm produces the protein, the protein gets out of the worm, and it is functionally active in the host. From that starting point, we can optimize the platform and think carefully about which diseases stand to benefit most from a delivery system that is continuous, targeted and long-lasting. That’s a fundamentally different kind of pharmaceutical biofactory platform, and we think it opens possibilities that are very hard to achieve with any other platform.”

Gut inflammatory diseases, including Crohn’s disease and ulcerative colitis, and food allergies are among the conditions Mitreva sees as strong candidates for future development. Diseases requiring small but sustained therapeutic concentrations, where compliance with repeated injections or infusions is a barrier, may also be well-suited to the platform. “Given the availability of controlled human infections, our disease-agnostic bioengineered hookworm platform offers a next-generation approach to address a suite of chronic human diseases, and with a single-dose administration, could potentially produce and deliver biologic medicines within the human host for years,” the authors wrote.

Although natural hookworm infection may cause only mild digestive symptoms in healthy adults, chronic infection with large numbers of hookworms can be dangerous for children, pregnant people and malnourished or otherwise vulnerable individuals. Infection can lead to anemia, poor growth and development, pregnancy complications and, in extreme untreated cases, heart problems or death.

This underscores the importance of keeping the infection strictly controlled for therapeutic use, Mitreva noted, which is possible because of the worms’ inability to reproduce without spending part of their life cycle in soil. “… as research progresses, it will be essential to ensure that these transgenic organisms do not have unintended ecological or human health impacts, maintaining a balance between innovation and safety,” the authors stated.

Mitreva noted that biocontainment strategies, such as engineering the worms to be unable to produce eggs, are under consideration to protect hosts and their environments as the platform advances. “Future studies can also address biocontainment of the genetically modified organism (GMO) by engineering suicide genes and/or inducible promoters into the transgene,” the team suggested.

The post Human Hookworm Engineered to Produce, Secrete Anti-Tetrodotoxin Antibody Into Preclinical Host Bloodstream appeared first on GEN - Genetic Engineering and Biotechnology News.

When Incyte agreed last year to partner with artificial intelligence (AI) platform developer Genesis Molecular AI to research, discover, and develop at least two small molecule treatments, they designed a collaboration that would generate at least up to $620 million for Genesis, whose foundation models for molecular AI are designed to power agentic drug design and development.

The companies now say they made enough progress over the past 15 months to expand their AI-based drug collaboration to encompass at least five targets—with a potential payoff for Genesis that has ballooned to over $1 billion.

Behind that expansion, Incyte and Genesis say, is the promise shown so far by the two initial targets, both selected by Incyte as called for in the initial strategic collaboration. One is a “very hard-to-drug, novel target” for which the companies worked to create novel, first-in-class chemical matter, while the other is a target that other companies have sought to make druggable without success, Pablo J. Cagnoni, MD, Incyte’s president and global head of R&D, told GEN.

“Novel targets create problems for obvious reasons. You don’t have any chemical matter that you know to start with. The collaboration with Genesis has jump-started that program significantly,” Cagnoni said of the first target. “You need a crystal structure, you need to know which particular site in the target you need to bind, and then you need to start making chemical substance against it.”

“It’s easy to make chemical matter, it’s really hard to make medicines—so that was the optimization step that Genesis really helped us do,” Cagnoni added.

The second target, he explained, required not only high potency and very high selectivity, but unique pharmaceutical and pharmacokinetic properties. The companies were able to incorporate those and other properties for the target with help from Genesis’s generative and predictive AI platform, Genesis Exploration of Molecular Space (GEMS).

GEMS integrates AI and physics into models designed to generate and optimize drug molecules. GEMS’ generative diffusion model for structure prediction, Pearl—short for “Placing Every Atom in the Right Location”—was unveiled in an October 26 preprint showing it to have surpassed AlphaFold 3 and other open source baseline models on the public protein-ligand co-folding benchmark Runs N’ Poses (14.5% improvement) and the docking and molecular generation benchmark PoseBusters (14.2% improvement).

‘Substantial progress’

“By being able to optimize multiple parameters at the same time with the help of the GEMS platform and our colleagues at Genesis, we were able to really make substantial progress that was eluding us with other technology,” Cagnoni said. “The collaboration with Genesis has allowed us to make significant progress on the path to an IND. We’re not quite there, but we’re getting pretty close to that.”

The two targets, he said, represented opposite ends of the drug discovery spectrum: “For one, we had something that started to look like a drug but wasn’t good enough. For the other one, we had a great target and no drugs. So, taking a view of those two ends of the spectrum, convinced me that we had to expand this, make it as broad as possible, and that’s why we put in place a new collaboration.”

As with their initial collaboration, the companies aren’t yet revealing the targets or therapeutic areas in which they are working, though Cagnoni said they fall within one of Incyte’s three current therapeutic areas of interest: hematology, oncology, and inflammation and autoimmunity, a narrower niche within the traditional I&I (inflammation and immunology) focus area.

Through the expanded collaboration, Incyte will use its proprietary experimental data to train Genesis’ GEMS platform, with the aim of accelerating drug development across multiple programs.

Options beyond five targets

Incyte will select at least five new targets to develop with Genesis, with options to nominate additional collaboration targets over time. Incyte will have exclusive rights to develop and commercialize treatments developed through the collaboration.

“We know what properties a priori we need to optimize for, always with some caveats,” Feinberg said. “We almost always know that we need to achieve potency, selectivity, a wide variety of ADME [absorption, distribution, metabolism, and excretion] properties. Usually, in a given program, something like 30 or so different ADME assays are routinely run to some degree of frequency. This can often feel like playing whack-a-mole, instead of the serious engineering task of multi-parameter optimization.”

“Our aim,” he added, “is to render the drug discovery process as much like the latter and as little like the former.”

Incyte has agreed to pay Genesis $120 million upfront—to consist of $80 million cash and a $40 million purchase of Genesis’ equity—and unspecified recurring research funding to support AI model training and inference computing. Incyte has also agreed to pay genesis up to $232 million in payments per target, tied to achieving preclinical and clinical development, regulatory, and sales milestones.

The collaboration is the second AI-focused partnership announced by Incyte in late May. A day before the Genesis expansion announcement, Incyte said it had launched a separate strategic collaboration with Edison Scientific to employ its Kosmos AI platform for discovery and development work—namely enabling continuous learning from translational and clinical data, real-time synthesis of evidence and predictive models of therapeutic performance.

Incyte and Edison disclosed the focus of their initial project: “high-impact” use cases in target discovery and validation and translational biology, where Edison’s AI capabilities will be embedded within Incyte’s research workflows. The companies said they aim to support more efficient exploration of experimental, clinical, and biomarker data with the potential to expand across Incyte’s broader R&D organization.

As for Incyte’s collaboration with Genesis, if Genesis achieves all milestones across the five initial targets of the expanded partnership, including multiple indications and major territories, Incyte will pay the company more than $1 billion—as long as the aggregate peak annual net sales of the five products exceed specified milestones. Payments could grow to “several” billion dollars depending on how many additional collaboration targets are nominated, and how many milestones are achieved.

Genesis is also eligible to receive royalties on sales of any approved collaboration products.

Stanford spinout

Genesis spun out in 2019 from the Stanford University lab of Vijay Pande, PhD, co-founder and managing partner of the venture capital firm VZVC and a former general partner at Andreessen Horowitz (a16z) and founding general partner of its bio funds. Feinberg was a graduate student in Pande’s lab who co-invented and co-authored key peer-reviewed papers detailing deep learning technologies.

In 2020, Genesis won a $52 million Series A financing. The company has grown since then to raise $340 million, most of that consisting of $200 million Series B financing completed three years later, plus the $40 million strategic investment Incyte made in Genesis equity as part of the companies’ expanded partnership.

In addition to a16z, Genesis’ investors have included NVentures, the venture capital arm of AI chip giant Nvidia, which has expanded in recent years into biopharma among other industries.

Incyte is the fourth and latest biopharma giant to partner with Genesis on an AI-focused drug discovery and development collaboration applying GEMS. Genesis garnered $35 million upfront in launching its partnership with Gilead Sciences in 2024, and earlier announced past collaborations with Eli Lilly and Genentech, a Member of the Roche Group.

“Our mission at Genesis is to create AI technologies that enable creating drugs that otherwise would not be possible,” Evan Feinberg, PhD, Genesis’ founder and CEO, told GEN. “And thanks to working with really, really elite drug discovery teams, like what Incyte has, we’re able to work on a wide spectrum of very important problems in drug discovery.”

That work, he asserted, requires discerning the uniqueness of each potential target.

“Every target is really its own special snowflake in some way. Every drug target really entails its own challenges, oftentimes requires its own special approach,” Feinberg said. “Over the past year, we were able to work on two very different programs, that each have their own challenges, and thereby enable us to adapt and deploy our GEMS AI platform in these very different settings, bringing one of those two targets much closer to IND, and for the other target finding the first-in-class chemical matter, which was a very exciting year of work.

“Now we’re excited to address the challenges ahead with this, expanded partnership together,” Feniberg added.

The post Small Molecules to Big Partnership: Incyte, Genesis Expand AI Collaboration to $1B+ appeared first on GEN - Genetic Engineering and Biotechnology News.

TSC-101 is designed to treat residual disease and prevent relapse in patients with AML and MDS undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The therapy candidate uses a gene modification approach to engineer T cells from a healthy donor into a patient-specific cell therapy product. As TScan advances TSC-101 toward a pivotal trial, which is expected to begin in the second quarter of 2026, the company is evaluating Cellares’ automated manufacturing platform as a scalable and economical path to future commercial demand.

Under the agreement, Cellares will automate the TSC-101 manufacturing and testing processes on the Cell Shuttle, its end-to-end manufacturing platform, and the Cell Q, its automated quality control and release testing system. These closed-system, fully automated workflows are designed to reduce process variability, minimize labor intensity, and enable consistent execution across runs and geographies, according to a Cellares official.

“As we prepare for the initiation of our pivotal study of TSC-101 this quarter, we are increasing our efforts for commercial readiness. Establishing a scalable and cost-efficient manufacturing strategy is a critical component. Cellares’ fully automated Cell Shuttle platform represents a promising approach to automating and scaling cell therapy production, with the potential to reduce manual processes and eliminate capacity constraints,” said Ray Lockard, chief manufacturing and quality officer of TScan Therapeutics.

“Through this evaluation, we aim to determine how this technology could strengthen our long-term manufacturing network and support broader patient access, supporting our goal of delivering transformative therapies to patients as efficiently and reliably as possible.”

“Patients with AML or MDS who remain at risk of relapse following transplant represent exactly the kind of underserved population that automated manufacturing was designed to reach,” added Fabian Gerlinghaus, co-founder and CEO of Cellares. “Bringing automation to a late-stage program like TSC-101, with its healthy donor-derived but patient-specific manufacturing model, is the kind of challenge the Cell Shuttle and Cell Q were built for, and we believe it represents the manufacturing economics any developer will need to reach a population of this scale.”

The agreement adds TCR-engineered T cell therapies to Cellares’ portfolio of automated cell therapy modalities, which includes CAR T cell therapies, hematopoietic stem cell programs, and autologous progenitor T cell therapies.

The post Cellares and TScan Agree to Evaluate Automated Manufacturing TSC-101 for Patients with Hematologic Malignancies appeared first on GEN - Genetic Engineering and Biotechnology News.