Biotech – Page 27 – Relatix Bio

May 13, 2026

Synthesizing a Natural Sunscreen and Antioxidant in E. coli

Researchers at Jiangnan University have engineered microbial “cell factories” to sustainably produce the UV-protective compound gadusol, a compound that could eventually serve as a sunscreen ingredient and an antioxidant additive.

Found in the eggs of various fish and other marine organisms, gadusol helps protect against ultraviolet damage. However, “it is scarce in nature, and extracting it is inefficient and can carry environmental costs,” said research lead Ping Zhang, PhD. “We want to find a scalable and greener way to produce gadusol.” Previous efforts to acquire gadusol have relied mainly on extraction from fish eggs or tissues at specific developmental timepoints. For their reported study, rather than harvest the molecule from nature, the team turned microbes into mini chemical factories, increasing yield more than 90 times.

The researchers reported on their developments in Trends in Biotechnology, in a paper titled “Multidimensionally engineered Escherichia coli for efficient gadusol biosynthesis with high-throughput quantitative analysis, in which concluded “This work provides valuable insights into gadusol biosynthesis and establishes a solid basis for future investigations into the feasibility of its industrial applications.”

How do fish survive sunlight in the open waters without getting burned? They make their own natural sunscreen. Gadusol is “a naturally occurring cyclohexenone compound that has attracted significant attention due to its potent UV-absorbing properties and broad biological functionalities,” the authors wrote. “Gadusol, as a cyclohexenone compound with potent antioxidant and biological properties, has shown significant potential for applications in pharmaceuticals, cosmetics, and nutraceuticals.”

The compound has been identified in the eggs of various fish species, including zebrafish, salmon, and sturgeon, as well as in coral reef ecosystems, where it shields marine embryos and coral from UV radiation. Moreover, the researchers explained, “Beyond its photoprotective role, gadusol also demonstrates pronounced antioxidant activity, with extracts from fish eggs exhibiting free radical scavenging capacity comparable to that of ascorbic acid under physiological pH and even superior chain-breaking activity against peroxyl radicals.”

However, the team pointed out, extracting gadusol from fish eggs is labor intensive and costly, and results in low yields. For their newly reported study the team rebuilt a zebrafish’s pathway for making gadusol inside the bacterium Escherichia coli, then tweaked the microbes’ genetics and growing conditions. “In this study, we constructed the gadusol biosynthetic pathway in E. coli and established an integrated engineering strategy to enable its efficient production,” they noted.

These modifications increased gadusol yield by nearly 93 times, from 45.2 milligrams per liter to 4.2 grams per liter. The compound’s antioxidant property inspired a useful shortcut, in the form of a color-based screening test. In the test, a purple chemical signal turns yellow when gadusol neutralizes free radicals. This color shift allows researchers to quickly identify bacterial strains that produce more of the compound. “Compared with traditional chemical analysis, this approach is more convenient, efficient, and economical,” said senior author Ruirui Xu,” PhD. “In addition, an efficient downstream process for gadusol extraction and purification was established, strengthening the translational potential of this platform,” the authors noted.

Producing gadusol through a microbial cell factory for sun protection. [Science Center for Future Foods, Jiangnan University]

The lab-made compound showed promise in preliminary UV-protection tests. “Achieving this level of production in the lab is very promising,” says Zhang. “It suggests that we may be able to meet future demand for natural sunscreen ingredients through microbial production.” The compound may offer more than just sun protection. In experiments, gadusol showed antioxidant activity comparable to that of vitamin C, suggesting it may help neutralize cell-damaging free radicals from UV exposure.

In their paper the authors suggested that “Beyond laboratory-scale optimization, this work demonstrates a practical and scalable route for manufacturing gadusol, a natural, nontoxic UV-protective, and antioxidant cyclohexenone.” The research comes amid growing interest in alternatives to some conventional sunscreen ingredients, which can irritate sensitive skin, harm marine organisms, or rely on petrochemicals. Gadusol’s combination of UV protection and antioxidant activity could make it an attractive ingredient for sunscreens and skin-care products. The team in addition pointed out, “By enabling sustainable microbial production independent of marine extraction, this strategy provides a renewable alternative to synthetic UV filters and antioxidants that may raise environmental or health concerns.”

But gadusol won’t make it into our beach bags just yet. The study did not compare gadusol head-to-head with commercial sunscreens, nor assess long-term safety or large-scale manufacturing. Regulatory approval would also be needed. Still, Xu believes that the research provides a starting point for moving gadusol toward practical applications. Based on current technology, he expects to start seeing some products appear on the market within two years.

“For small molecules with application potential, we hope people look beyond traditional extraction methods,” Zhang commented. “Microbial cell factories are emerging as a greener and more sustainable way to bring laboratory discoveries into real-world use.”

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May 13, 2026

ApexGO: AI-Driven Approach to Faster Antibiotic Discovery

Antibiotic resistance is on the rise around the world, creating an urgent need for faster and more dependable approaches to design antimicrobial candidates. While AI-driven methods have accelerated antimicrobial discovery, most have focused on screening fixed libraries or generating broad candidate sets.

Now, researchers at the University of Pennsylvania have developed ApexGO—a novel, AI-powered method that starts with a small number of candidates and improves them, using a predictive algorithm to evaluate each modification and guide the next.

“Antibiotic discovery is fundamentally a search problem across an enormous molecular space. ApexGO gives us a way to navigate that space with far more direction,” says César de la Fuente, PhD, presidential associate professor in the School of Engineering and Applied Science at UPenn.

This work is published Nature Machine Intelligence in the paper, “A generative artificial intelligence approach for peptide antibiotic optimization.”

“What is striking is that ApexGO’s predictions held up in the real world,” says Jacob R. Gardner, PhD, assistant professor in computer and information science (CIS) at UPenn. “ApexGO was optimizing against another computer model, so one concern was that it might find molecules that looked good to the model but failed in the lab. Instead, the majority of the molecules it designed actually worked.”

indeed, 85% of the AI-generated molecules halted bacterial growth, while 72% outperformed the peptides from which they were derived. In mice, two antimicrobial peptides created by ApexGO reduced bacterial counts at levels comparable to the antibiotic polymyxin B.

“This result points toward a future in which we can optimize molecules for a desired function in a fraction of the time,” adds de la Fuente, “using machines to guide discovery through chemical spaces too vast for humans to explore by trial and error.”

For years, the de la Fuente lab has looked for antibiotic candidates in unlikely places, from frog secretions to ancient microbes. Two years ago, the group released APEX, an AI model that predicts whether or not a given peptide is likely to have antimicrobial properties.

“APEX helped us find promising antibiotic candidates in enormous biological datasets,” says Marcelo Torres, PhD, research assistant professor of psychiatry in the Perelman School of Medicine. “ApexGO takes the next step: once we have a promising molecule, it helps us ask how to make it better.”

One part of ApexGO (short for APEX Generative Optimization) suggests molecular tweaks, while the previously published APEX model predicts whether those changes are likely to increase antimicrobial activity. ApexGO then uses those predictions to guide the next round of proposed edits.

While some of the molecules proposed by ApexGO showed promising antibiotic activity, the researchers emphasize that even the best-performing peptides are still early-stage candidates. Before any could be used to treat infections in humans, they would need to be further optimized for safety, stability, and how long they remain active in the body.

Still, the study suggests that AI can help researchers decide which molecules are worth making and testing in the first place. For de la Fuente, the approach could eventually extend beyond antibiotics. “In this case, we wanted to optimize peptides for antimicrobial activity,” he says. “But you could imagine applying the same idea to peptides with other biological functions, like modulating the immune system or targeting tumors.”

“ApexGO shows that AI can do more than predict which molecules might work: it can help us improve them,” adds de la Fuente. “At a time when antibiotic resistance is rising worldwide, we need technologies that help us move faster from an idea to a real therapeutic candidate. ApexGO is an important step toward that future.”

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May 13, 2026

Why AI Alone Isn’t Enough for Oligonucleotide Discovery

AI is reshaping drug discovery, and nucleic acid–based medicines, including mRNAs, gene therapy, and oligonucleotide therapeutics, are no exception. By optimizing sequences and chemical modifications for experimental testing, AI accelerates discovery timelines, which is particularly critical for oligo therapeutics, a modality central to the n=1 rare diseases, which afflict mostly young patients for whom there is additional urgency.

However, a familiar caveat remains: AI is only as powerful as the data from which it learns. How can we provide enough high-quality input data to fuel this engine and design next-generation precision medicine?

A typical workflow for developing an AI-powered oligo predictive model begins with collecting experimental outcomes of oligo sequences, with each sequence annotated using a defined set of features. This data is then used to train AI models that identify patterns associated with improved activity and safety.

However, as is often the case with pioneering technologies such as oligonucleotides, the scarcity of data is a major problem. To overcome this limitation, scientists trawl public resources such as publications and patents to extract this data. ASOptimizer, OligoAI, and eSkip-Finder are examples of newer oligo-predicting AI models that are trained using publicly available data.

While these models are advancing in the right direction, relying primarily on this data comes with several disadvantages, such as:

inconsistent experimental conditions between the datasets,
limited diversity in sequences and chemistries,
lack of negative data, and
insufficient coverage of critical information such as toxicity and off-target effects.

Furthermore, since data sourcing and annotating often require the use of automated, AI-powered tools, there is a risk of mislabeling and misinterpretation. As such, correlation statistics between predicted and experimental values for these models are not too high, generally hovering between 0.4 and 0.7.^{1,2, 3}

Building the data foundation for AI drug discovery

The most valuable training data is:

designed to span broad chemical space and probe critical safety features,
produced under controlled conditions,
consistently processed and annotated, and
generated in a controlled environment, ideally internally.

Large-scale screening campaigns are essential in that context as they provide the dense, reliable, datasets required to train AI models and extract meaningful insights for sequence and chemistry prediction.

Brett Monia, CEO of Ionis Pharmaceuticals, describes this reality as “hard, brutal screening–screening a lot of oligonucleotides with different decorations, different amounts of chemistries, different sequences. We have plenty of (design) rules, but we still don’t have enough.”⁴

One way to address this challenge is through intentional screening design: deliberately varying sequence motifs and positional chemistries within screening libraries to systematically explore chemical landscapes and expand the empirical foundation on which both rules and AI models are built.

With the advent of faster and more affordable transcriptomic technologies, high-throughput RNA-seq can now be incorporated into oligonucleotide screening workflows. This method enables the systematic detection of off-target effects, including those that arise through mechanisms beyond straightforward.^5,6

While these approaches generate large and complex datasets, they represent a critical investment—one that lays the foundation for a faster, more efficient, and ultimately more cost‑effective future of oligo discovery.

Digital infrastructure, engineering AI-ready data at scale

While generating large datasets may be hard and brutal, managing, curating, and analyzing them doesn’t need to be. For data to be truly reliable and trustworthy, quality must be engineered from the start. Important aspects to consider include:

A single source of truth–a centralized FAIR data repository, where all data is systematically stored and governed for controlled access and use;

Comprehensive metadata capture, including protocols, batch numbers, and reagent references to ensure results can be interpreted correctly and are not driven by experimental artifacts;
Automated quality control and data analysis of large screens for large‑scale screens, ensuring consistent, efficient, and reproducible data processing; and
Consistent ontology and nomenclature for oligo sequences and their chemistries, as exemplified by Roche’s open-source tool (HelmShaker) for translating molecules into HELM notation.

In practice, these principles are implemented through integrated digital infrastructures that combine molecular registration systems with automated analytics across diverse experimental modalities such as high‑throughput screening, next‑generation sequencing, mass spectrometry, and chromatography.

Such approaches are increasingly used across the pharmaceutical and biotechnology sectors to manage oligonucleotide ADME, process development, and screening data, thus helping teams maintain data integrity and continuity throughout the oligo discovery and development lifecycle.

AI promises to redefine what is possible in oligo discovery, and the field is already beginning to see its impact. But AI alone is not the breakthrough—data is. Only large, high‑quality experimental datasets, generated intentionally and prospectively, can unlock AI’s full predictive power.

Organizations that invest early in both systematic data generation and robust data infrastructure will be best positioned to lead the next wave of oligonucleotide discovery. This shift is especially urgent for n = 1 rare diseases, where speed, precision, and learning from every experiment can make the difference between possibility and progress.

Ming Wang, PhD, is scientific business manager at Genedata.

References:

¹Hwang, G., Kwon, M., Seo, D., Kim, DH., Lee, D., Lee, K., Kim, E., Kang, M., Ryu, JH., ASOptimizer: Optimizing antisense oligonucleotides through deep learning for IDO1 gene regulation. Mol Ther Nucleic Acids. 2024 Apr 6;35(2):102186. doi: 10.1016/j.omtn.2024.102186

²Chiba, S., Lim, KRQ., Sheri, N., Anwar, S., Erkut, E., Shah, MNA., Aslesh, T., Woo, S., Sheikh, O., Maruyama, R., Takano, H., Kunitake, K., Duddy, W., Okuno, Y., Aoki, Y., Yokota, T. eSkip-Finder: a machine learning-based web application and database to identify the optimal sequences of antisense oligonucleotides for exon skipping. Nucleic Acids Res. 2021 Jul 2;49(W1):W193-W198. doi: 10.1093/nar/gkab442

³Hill, B., Jaques, M.R., Nair, RR., Whiffin, N., Wood, MJA., Sanders, SJ., Oliver, PL., Hill, AC., Rinaldi, C. Accurately modelling RNase H-mediated antisense oligonucleotide efficacy. bioRxiv. 2025 Oct 30. https://doi.org/10.1101/2025.10.29.685292

⁴Accelerating Oligonucleotide Therapeutics. Evotec eBook.

⁵Pekker, D., Kuntz, S., McArthur, M., Nicholson-Shaw, T., Yanke, S., Mukhopadhyay, S. A Dose-Response Model for Accurate Detection and Quantification of Transcriptome-Wide Gene Knockdown for Oligonucleotide-Based Medicines. bioRxiv. 2024 May 29. https://www.biorxiv.org/content/10.1101/2024.05.28.596270v1.full.pdf

⁶In-silico siRNA Off-Target Predictions: What Should We Be Looking For? OTS Oligonucleotide Therapeutics Society, Webinar, 2024 May 2

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May 13, 2026

Cellares and ProTgen Automate Manufacturing of Progenitor T-Cell Therapy for Blood Cancer

Cellares, an Integrated Development and Manufacturing Organization (IDMO) that combines automated manufacturing platforms with global Smart Factory infrastructure, and ProTgen, a therapeutic company pioneering targeted Notch activators to reactivate the thymus and reconstitute the adaptive immune system, have announced a partnership to automate manufacturing and quality control of ProT-096, ProTgen’s personalized progenitor T-cell therapy for patients with refractory leukemia and other hematologic malignancies. In this collaboration, Cellares will apply the company’s Cell Shuttle and Cell Q platforms to ProT-096 while providing regulatory support toward IND submission.

Fabian Gerlinghaus, co-founder and CEO of Cellares, says hematologic malignancies have waited too long for cell therapy to deliver on its promise, with manufacturing complexity being one of the main bottlenecks. ProT-096 represents “exactly the kind of innovative program” for which Cellares was founded.

“Early-stage developers should not have to choose between advancing their science and securing the manufacturing foundation they need to scale,” said Gerlinghaus. “By automating the manufacturing process and providing regulatory expertise toward IND submission, we can help ProTgen move faster and with greater confidence toward the clinic.”

Patients with refractory hematologic malignancies often face a compromised immune system following intensive treatment. While ProT-096 mandates precision manufacturing at scale, achieving the reproducibility, process consistency, and cost efficiency needed to support clinical development requires advanced manufacturing approaches.

Cell Shuttle’s automated, end-to-end manufacturing workflow reduces manual touchpoints, minimizes variability, and enables standardized execution across runs, equipment, and facilities. Combined with Cell Q, the workflow is designed to meet the demands of clinical- and commercial-scale production while maintaining quality standards for GMP manufacturing. The partnership also adds personalized progenitor T cells to Cellares’ platform capabilities across CAR T-cell therapies and HSC programs.

ProTgen’s proprietary targeted Notch activator platform programs cell fate both in vivo and ex vivo. The company’s initial focus is to reactivate the thymus and rebuild a diverse, functional immune repertoire for patients with compromised or aging immune systems.

Carter Cliff, CEO of ProTgen says ProT-096 represents a new approach to immune reconstitution, with the potential to address a significant unmet need for patients whose immune systems have been severely compromised by hematologic malignancy and prior treatment.

“This partnership allows us to pair our targeted Notch activator platform with an automated, scalable manufacturing foundation designed to support the path toward IND submission and, ultimately, clinical development,” he said.

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May 13, 2026

Adopting Creative Chemistry to Optimize Bioprocessing Workflow

Taking a creative approach to chemistry can help developers of antibody-drug conjugates (ADCs) improve the stability and purity of their products. That’s the view of Sunny Zhou, PhD, professor of chemistry and chemical biology at Northeastern University. Zhou will be speaking at the Bioprocessing Summit in Boston in August.

According to Zhou, the structure of ADCs can make them vulnerable to bioprocessing issues that don’t affect traditional antibodies. As one example, he says, the payloads of antibody drug conjugates often significantly absorb above 280 nm, making them markedly more sensitive to light.

“There’ll be photochemistry induced by the payload that can damage both the antibodies and payloads, such as crosslinking that likely leads to aggregation,” he says. “We’ve already published some work showing light-induced protein modifications, crosslinking, and aggregation.”

According to Zhou, some initiatives are already underway to address this issue. For example, by engaging in antibody production and downstream processing in dim or safe light (e.g., yellow or red light) instead of the more commonly used bright white light.

Another issue, he says, is that the linker connecting the antibody and drug payload is designed to be cleaved by enzymes in human patients. On the other hand, it also means that similar enzymes in host cell proteins (HCPs) may prematurely cleave the linker during production and storage, thereby decomposing the drug and contaminating the final product.

“Many host cell proteins contain such enzymes, but they don’t cleave antibodies. With these ADC linkers, however, enzymes that didn’t create problems before might do so now,” he says.

Zhou explains that premature cleavage of ADC linkers has been observed in an industrial setting. Fortunately, he says, his research team, in collaboration with companies like Takeda, is already creating universal platforms and workflows to identify and effectively remove these potential HCP contaminants, as well as working to better understand the stability of the linkers.

“These drugs circulate in the body for maybe two to three weeks, and stability issues can be amplified during circulation,” he says. “So, making the linker more stable [during manufacturing] may also help improve stability during circulation, further down the line.”

Zhou’s team is now hoping to look at other creative chemistries in bioprocessing. Among these is, for example, removing reagents, by-products, and impurities by filtration, which may be faster than relying on chromatography, he says.

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May 13, 2026

Yeast We Can Cut Costs By Optimizing Cell-Free Expression Systems

Choosing the right additives could help “cell-free” expression systems finally fulfill their potential and provide biopharma with a low-cost way of making protein drugs, according to a recent research report.

The new study looked at how cell-free systems, in which biochemical reactions occur independently of cells, could be fine-tuned to provide drug makers with alternatives for large-scale protein production.

And the potential of the approach is significant, says Karen Polizzi, PhD, a professor from the department of chemical engineering at Imperial College London, who adds, “Cell-free protein synthesis (CFPS) is a flexible manufacturing technology. It can be used for on-demand synthesis in low-resource environments or to make difficult-to-express products, especially medicines that are toxic to the cell. Cell-free reactions scale well across microliter to liter scale without needing adjustments.”

The Imperial team’s research focused on expression systems based on the yeast species Pichia pastoris, which, as Polizzi explains, “has machinery capable of post-translational modifications of proteins that can be necessary for function.”

As an expression host, P. pastoris combines elements of both prokaryotic and eukaryotic systems, such as a rapid growth rate and the ability to perform post-translational modifications (PTMs).

The problem is that current commercially available Pichia systems are only able to produce low amounts of protein. According to Polizzi and her co-authors, the productivity of P. pastoris-based cell-free systems usually ranges from 6 to 100 µg/mL, which is only approximately five percent of that achieved by comparable E. coli systems. In addition, the additives required by Pichia-based systems are more expensive than those required by equivalent platforms.

Additives to improve yields

To address this, Polizzi and co-authors systematically evaluated a variety of chemical additive combinations to identify the most effective stabilizers and crowding agents to be incorporated in the reaction.

The researchers also used a machine learning model to predict translation initiation rates and optimized the Kozak sequence—the protein translation initiation site in most eukaryotic mRNA transcripts—to enhance expression.

In addition, the Imperial team evaluated lower-cost glycolytic intermediates as substrates for ATP regeneration to reduce the cost of goods.

Polizzi says, “We focused on how to improve the yields and reduce the cost of production. We identified some additional additives that boost the yield without substantially increasing the cost. We also identified a different energy source that can be used.”

She adds, “This work underscores the importance of protein-stabilizing additives and the role of rationally designed DNA sequences with minimized mRNA structural complexity to enhance yield in CFPS. Our demonstration of glycolytic intermediates as a potential secondary energy system additionally provides the foundation for the development of a cost-effective P. pastoris CFPS.”

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May 13, 2026

Operator Protection as Core Design Principle for ADC Bioprocessing

Antibody-drug conjugates (ADCs) continue to gain momentum as one of biopharma’s most promising therapeutic classes, particularly in oncology. But while the science behind ADCs advances rapidly, manufacturing these highly potent therapies forces two requirements to coexist: strict aseptic processing and high-containment handling of highly potent active pharmaceutical ingredients (HPAPIs).

For Ashley Harp, a fellow in containment and bioconjugates at the consultancy CRB, operator protection is not simply an environmental health and safety issue—it is a core design principle for successful ADC bioprocessing.

“One of the primary concerns in ADC bioprocessing is protecting operators from exposure to highly potent compounds, which can exist in both solid and liquid form,” Harp says. “Those risks extend far beyond the core manufacturing team to include quality control, maintenance, and calibration staff—anyone who may interact with the process or equipment over its lifecycle.” That broader view is increasingly important as commercial bioprocessors scale ADC production.

Potential exposure points abound. “Across all stages of ADC bioprocessing, additional risks are associated with handling solid and liquid waste, collecting samples, changing or maintaining HVAC filters, and performing maintenance or calibration activities,” Harp says. These tasks often involve residual potent compounds that remain on equipment surfaces or within process systems, creating exposure risks long after active manufacturing ends.

Tackling those risks starts long before production begins. “Addressing operator protection risks starts with rigorous risk assessments and the implementation of recommendations based on those assessments,” Harp says.

She emphasizes the importance of involving experts in containment, industrial hygiene, and collaborative facility and equipment design early in project planning. Identifying hazards upfront makes it easier—and less costly—to build effective safeguards into the process rather than retrofitting them later.

Where higher-risk activities cannot be avoided, Harp recommends multiple layers of protection rather than relying on a single solution. Closed processing systems, equipment designed to contain materials at the source, and technologies that support safe cleaning and transfer all play a role. Examples include rigid and flexible containment approaches, containment valves, split valves, specialized piping systems, continuous liners, containment enclosures, spray balls, wash wands, and manual wiping protocols.

At the same time, smarter process design can reduce risk even further. “In parallel, thoughtful process development can reduce or even eliminate the need for direct personnel interaction with the manufacturing process,” Harp says. Technologies such as flow chemistry, process intensification, and robotics can significantly reduce manual handling and intervention, limiting the chances of exposure while also improving consistency.

For commercial bioprocessors, implementing these solutions requires organizational alignment. “Successfully implementing these solutions requires early and ongoing collaboration across disciplines,” Harp says. Environmental health and safety, industrial hygiene, maintenance, calibration, operations, engineering, and quality teams all need to be involved from the beginning to form truly cross-functional design teams.

Facilities must also remain flexible. ADC pipelines evolve quickly, and containment strategies need to evolve with them. Specialized expertise in integrating process equipment within high-containment environments is crucial, as are strong R&D capabilities—or partnerships that can provide them.

Although “high containment requirements inherently increase the operational cost and complexity of manufacturing ADCs compared to non-potent therapies,” Harp argues that strategic improvements can offset some of those costs over time. Process intensification, reduced manual handling, and stronger containment can improve raw-material efficiency and reduce waste generation. Implementing new systems might initially extend development timelines or delay time to market, but the long-term result can be safer, more sustainable operations for both people and products.

As ADC pipelines continue to expand, operator protection is shifting from a compliance checkpoint to a competitive necessity.

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May 13, 2026

Technique Yields Uniform, High-Quality, EVs at Scale

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) play an outsized role in intracellular communications, influencing such functions as inflammation and tissue repair. With the possible applications of these small, membrane-bound particles growing, an efficient, cost-effective production method has been on drug manufacturers’ wish lists for some time.

A novel, streamlined chromatographic production and isolation method developed by scientists at Satorius BIA Separations in Slovenia may fulfill that wish, yielding uniform, high-quality EVs at scale. The method concentrates MSC-EVs directly from conditioned media. It also removes 97% of protein impurities and 95% of double-stranded DNA-related impurities, increasing their potential as therapeutics or drug delivery vessels.

Microcarrier + suspension

The method relies upon preferential exclusion chromatography, Katja Vrabec, head of product application area (EVs) at Sartorius, notes in a recent paper. In it, Vrabec and colleagues explain the method “uses monolithic hydroxyl columns to purify and concentrate the MSC-EVs,” and biochromatography analytics to track EV-specific surface antigens.

First, the team expanded the MSCs in growth media, and then produced the EVs in a lean media formulation to limit production of protein and particle contaminants. That part is standard.

Here’s what’s different: The scientists used a microcarrier-based system rather than flask-based 2D cultivation to scale the MSC cultures and increase the ratio of EVs to contaminants in conditioned media. They also used a suspension culture to enhance cell growth surface-to-volume ratios, and thereby increase EV yield. Then, they used a monolithic hydroxyl column to capture and purify the EVs directly from harvest.

Increasing cell density and the cell-to-impurity ratio lowers buffer consumption downstream and lays the groundwork for biomanufacturers to transition to a scalable bioreactor system.

Because the main impurities in EV harvests don’t interact with the chromatographic column in high-salt-binding conditions, the team recommends choosing a low-salt buffer for elution to reduce the need for buffer exchange before the polishing step. The optimal binding condition, they report, is “sodium citrate of 0.75M at pH 7.0.”

This research highlights the need to consider upstream and downstream processing as a cohesive system, to design a simple, scalable, holistic process, and to apply reliable analytics. This all is particularly challenging, the team admits, given “the heterogeneous nature of EVs and the presence of similarly-sized components in biological samples.”

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May 13, 2026

“It Was Not a Cure”: Musunuru Cautions ASGCT on Baby KJ Promise

BOSTON – When Kiran Musunuru, MD, PhD, walked to the microphone to deliver remarks on behalf of the team that won the American Society of Gene and Cell Therapy (ASGCT) 2026 Catalyst Award, most of the thousands of attendees surely expected a feel-good speech.

After all, it was 12 months ago that Musunuru, addressing the same convention in New Orleans, shared the exciting news regarding the delivery of a bespoke base editor to an infant, Baby KJ, with a rare urea cycle disorder. Musunuru and his colleague, Rebecca Ahrens-Niklas, MD, PhD, were recently named to the TIME 100 Most Influential People of 2026. “A decade from now,” stated Nobel laureate Jennifer Doudna, PhD, “their names will be in medical textbooks, not only for Baby KJ, but for opening the door to personalized genetic medicine for thousands of children after him.”

Musunuru and Ahrens-Niklas, from the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP), respectively, were honored alongside Doudna’s colleague Fyodor Urnov, PhD (Innovative Genomics Institute) and Danaher Corporation, for building the remarkable academia-industry consortium that designed and delivered the gene editing therapy, resulting in Baby KJ’s discharge from CHOP and a wave of national television appearances.

Indeed, Musunuru opened his ASGCT remarks in upbeat mood. “The potential is there to [deliver personalized therapies] over and over again for hundreds of diseases centered in the liver.” But halfway through his speech, Musunuru’s tone changed. While most grateful for the recognition from ASGCT, he said it was important to always “be your own worst critic.”

“I’ll be brutally honest,” Musunuru said. Despite the unquestionable “enthusiasm and excitement” surrounding the Baby KJ story, “there are some profound limitations. It was not really science at all!” Musunuru continued. “It was not a clinical trial. It was not clinical research. It was not a cure.”

“The best we can say is we hope we’ve turned a devastating disease into a milder, manageable condition. But it’s too early to say that… This was a personalized N-of-1 therapy—we can’t say what this means for anyone.”

Drawing applause from the audience, Musunuru pushed on: “We mustn’t be snake oil salesmen or give false hope… We have a profound ethical responsibility not to mislead families over what is possible.”

“We don’t actually know anything,” Musunuru said. “We need to do clinical trials—scientifically and ethically.”

The path forward

Musunuru set the Baby KJ story in the broader context of his group’s work on phenylketonuria (PKU), one of the classic inborn errors of metabolism. A few years ago, Musunuru and Ahrens-Niklas set about designing gene editing therapies targeting the first and sixth most common PKU mutations using adenine base editors. (There are more than 1,000 known mutations that cause PKU.)

After testing in humanized mouse models, the researchers were delighted to see the phenylalanine levels rapidly drop to normal, sustained for the lifetime of the mice. Flush with funding from the Somatic Cell Genome Editing program at NIH, Musunuru and Ahrens-Niklas began talks with the U.S. Food and Drug Administration in February 2024 to settle the question: Do we need separate Investigational New Drug applications (INDs) for each PKU variant?

“It is basically the same drug, the same gene, the same disease, the same clinical endpoints. Can’t we cover both variants in a single IND and a single ‘umbrella’ clinical trial?” summarized Musunuru. The answer was “maybe”—the agency needed to consider the full implications of the proposal.

The Philadelphia team began to develop workflows for four more PKU mutations, leading them to propose an umbrella trial for a revised total of six variants. Following another meeting with FDA officials in early 2025, the response was extremely positive: a single IND application would be appropriate, with a single toxicology study conducted in a single species. The FDA also agreed to consider additional variants.

In parallel, Ahrens-Niklas and Musunuru were studying sick patients with urea cycle disorders. Although these are liver disorders, “the real harm happens in the brain,” Musunuru said, resulting from toxic levels of ammonia. Enter Baby KJ’s diagnosis with CPS1 deficiency, and the notion that there was chance to design a personalized therapy.

In the Fall of 2024, Musunuru and Ahrens-Niklas held a pre-IND meeting with FDA officials. The idea was to streamline applications for a group of urea cycle disorders caused by mutations in seven different genes.

The FDA judged that all seven therapies could be evaluated in a single Phase I/II trial, but separate INDs would be required for each gene. “We’d have to do it piece by piece,” Musunuru said. First, file a master protocol for urea cycle disorders; after that IND clears, then file additional gene-specific INDs and amend the original IND.

“This is how we can make the trial accessible to all UCD patients across the country,” he said.

Back to the future

Coming back to the present, Musunuru stated that although the primary IND had been filed, “this does not mean the trial is open or we can enroll patients.” Musunuru listed three major issues:

The team has not yet manufactured any gene therapy product.
As seven INDs are needed to fully open the clinical trial, it will be well into 2027 until all INDs are submitted.
In February 2026, the FDA issued a draft Plausible Mechanism Framework. Musunuru’s team held another pre-IND meeting with the FDA to advocate for the use of prime editing for urea cycle disorders. After all, Musunuru reasoned, why should therapies be restricted to base editing approaches (G-to-A substitutions) but not patients who harbor a G-to-C mutation? The FDA indicated that a separate IND/BLA would be needed for each gene, and that process validation should be finalized before any dosing of Phase II subjects.

The path forward, Musunuru said, was to adopt an adaptive, real-time clinical trial design. That involves testing therapies, then advancing therapies from proof-of-concept to the validation phase. At that point, if all goes well, they can submit a BLA. Ahrens-Niklas and Musunuru laid out more details of their approach and dealings to date with the FDA in a commentary published late last year entitled: “How to create personalized gene editing platforms.”

With that, Musunuru hastily closed and exited stage left to give a keynote address at another conference across the road.

The post “It Was Not a Cure”: Musunuru Cautions ASGCT on Baby KJ Promise appeared first on GEN – Genetic Engineering and Biotechnology News.

May 13, 2026

ASGCT 2026: Victoria Gray Roadshow Returns to Boston

BOSTON – The annual American Society of Cell and Gene Therapy (ASGCT) conference got underway in Boston this week with a guest appearance by one of gene therapy’s greatest ambassadors and patient advocates.

Victoria Gray, the sickle cell warrior who was successfully treated in the exa-cel clinical trial sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics seven years ago, spoke in an evening workshop organized by the Emily Whitehead Foundation and ScaleReady.

Boston is becoming a regular stomping ground for Victoria. Last November, she spoke at the Genetic Agency Technology Conference, hosted by Dyno Therapeutics. Last month, she finally received an invitation to visit the headquarters of Vertex and speak in a town hall meeting.

In an extemporaneous 20-minute speech, Victoria talked about her lifelong journey with sickle cell disease (SCD). She recalled her first major pain crisis, when she was a young girl—a lightning-type pain that began in one arm before traveling across her chest and down the other arm. “In minutes, my entire body was engulfed in pain,” she said. “The pain felt like getting struck by lightning and hit by a truck. It took me to the floor.” Her grandmother provided hot towels and Tylenol, but nothing worked—not even prayer. After a week in hospital, Victoria returned home but still felt fatigued.

Stricken by regular pain crises, a hallmark of SCD, Victoria encountered numerous disappointments growing up. Her hematologist said she could not join the cheer team. In eighth grade, she was told she could not join the basketball team, because the exertion would provoke a pain crisis. “As a kid, I was like a Timex: I could take a licking and keep on ticking,” she joked.

In high school, she signed up to join the United States Navy. “I wanted to serve my country,” Victoria recalled. As she was preparing for basic training, she learned that her disease prevented her from enrolling. “So that was another dream lost.” Next, she turned her attention to nursing. Victoria graduated high school in 2003, but it took another seven years before she could qualify for a nursing program. “Professors didn’t understand because I looked whole and complete. They didn’t think I was sick.”

In 2010, just before Halloween, Victoria had the worst pain crisis of her life, stripping her ability to walk or use her arms to feed herself. “I couldn’t do anything, facing some of the worst pain of my life. I was getting strong pain medicines like Dilaudid, ketamine, but still couldn’t move. Pain had taken over my thoughts.” Unable to sleep or even take a nap, Victoria was desperate to go home to her family.

Later, she asked the doctors if they had heard about a haplo-bone marrow transplant (BMT). “I can’t continue living like this,” she said. The doctors looked at each other and said no. After weeks of prayer, Victoria received a call from her hematologist. “Victoria, I have good news, but I only want to tell you in person.” For the first time in her adult life, Victoria was excited about a doctor’s appointment.

She traveled to Nashville with her brother, who would be her BMT donor, and her husband. She met Haydar Frangoul, MD, whom Victoria calls, “the nicest doctor that I’ve met in my adult life.” Frangoul told her: “Victoria, I wish I had met you ten years ago!’

Although Victoria’s brother was a suitable BMT match, Victoria was scared of the possibility of graft vs. host disease (GVHD). “My purple pill basket was filled to the brim with medicine every day. If I would acquire [GVHD], that basket would have to triple in size.”

“I’m a human!”

On her next visit to Nashville, she had to extend her stay because of another pain crisis. But that stay changed her life. Frangoul sat next to her bedside. “Victoria, have you ever heard of CRISPR?” he asked. Victoria shook her head.

Frangoul used a typo-in-a-textbook analogy and reassured Victoria that there was no chance of GVHD, because she would be receiving her own modified stem cells. “You’ll be the first person to do this, Victoria,” he said. “First human?” she asked. “Yes,” Frangoul said, “but it’s been tested in primates.”

“But I’m a human!” she said.

After being reassured that she could still try a bone marrow transplant if the procedure did not work, Victoria agreed to move forward. The chemotherapy, was “hell on Earth,” she recalled. “I lost my hair, which I was prepared for, but the mucositis, the sores in my mouth, the inability to eat for two weeks, was gruesome.”

Victoria swallowed her tears and decided to fight. This was the first time she had been in the hospital by her choice, to live for her children. About eight months after receiving her CRISPR-edited stem cells in July 2019, she woke up one morning, not feeling anything. “Oh my God, I’m dead,” she thought. She called her kids into the room and hugged them, slowly realizing that “this is what normal feels like.” For the first time in more than 25 years, Victoria did not have any pain in her lower back and hips. She was able to breathe deeply without wincing.

A few years after her therapy, Victoria was finally able to take her first ever flight, to Washington D.C. to visit her husband, who was on deployment. “It was the first time that I was ever able to show up for the man who has shown up for me,” she said. She has since watched her daughter dance in a Christmas parade and supported her son playing high school football. “The little things have brought me great joy,” she said.

Her second flight was a business class trip to London with her husband in March 2023, where she spoke at the third International Summit on Human Genome Editing. “I got to keep my covenant that I made with God, that God, if you do this for me, I would tell the world about what you did.”

Victoria welcomed her first granddaughter on Christmas Eve, 2024. Next week, another milestone: she will be in the audience as her twins graduate high school. And next month, she will publish a children’s book called Hema’s Journey, the tale of her inspiring journey with CRISPR gene therapy. She’s currently training for a group effort to climb Mt. Kilimanjaro.

Perhaps at next year’s ASGCT conference in Philadelphia, she will be invited to present in a plenary session on the main stage. It would be hard to think of a more fitting speaker.

The post ASGCT 2026: Victoria Gray Roadshow Returns to Boston appeared first on GEN – Genetic Engineering and Biotechnology News.