STAT+: Congress returns to a packed health care agenda

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Trump deleted an AI image of himself on Truth Social looking a whole lot like Jesus after conservative Christians cried blasphemy. “It’s supposed to be me as a doctor,” Trump told reporters while stepping out of the Oval Office to get a McDonald’s delivery. Send news tips and surprising health care angles to John.Wilkerson@statnews.com or John_Wilkerson.07 on Signal.

Recess is over

Congress returns to a packed health care agenda after two weeks off. Here’s what to follow.

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Down Syndrome Chromosomal Therapy Draws Closer

Gene editing has been able to silence the extra chromosome that is mostly responsible for Down syndrome (DS) in a cell-based study that could be the first step towards therapeutic treatment.

The approach uses a modified form of CRISPR-Cas9 to alter precise sections of DNA.

Researchers used this to insert the X-inactivation specific transcript (XIST) gene to deactivate X chromosomes in female cells, thereby correcting chromosomal triplication.

The partial transcriptional correction, reported in PNAS, offers a scalable, targeted platform for chromosomal therapy in Down syndrome and other aneuploidy disorders, which are conditions involving an abnormal number of chromosomes.

“These studies overcome a major hurdle in the treatment of Down syndrome (a genetic disorder cause by three rather than two copies of chromosome 21) by dramatically increasing the efficiency with which to insert XIST onto a single copy of chromosome 21 and thereby silencing this third copy,” senior researcher Volney Sheen, PhD, from Beth Israel Deaconess Medical Center, told Inside Precision Medicine.

“Determination of the best ways and times to deliver these constructs to the brain will become the next focus as we seek a clinical treatment for DS.”

Down syndrome is the most common genetic disorder and occurs in one out of 700 live births. It is linked with cognitive impairment, heart defects, and early-onset Alzheimer’s disease and results from the triplication of approximately 500 genes as well as other genetic changes on chromosome 21.

The XIST gene produces a long, noncoding RNA that inactivates many of the genes on one of the two X chromosomes of female mammals. It has therefore been mooted as a treatment for Down syndrome but technical limitations, including low levels of gene integration, have hindered progress.

In an attempt to address this, Sheen and team created a CRISPR-based method that involved fusing a codon-optimized λ-phage with Cas9, assembling single guide (sg)RNAs specific to single nucleotide polymorphisms (SNPs), and enhancing donor-acceptor DNA pairing.

The modified CRISPR-Cas9 method achieved a high level of genomic integration of large genetic material, improving the efficiency and specificity of XIST integration.

Inserting XIST onto one of the trisomic chromosome 21 alleles using SNP-dependent sgRNAs achieved an integration efficiency of 20% to 40% for the 14kb XIST gene.

XIST integration was revealed through expression of the enhanced green fluorescent protein reporter, clonal sequencing of individual lines, and fluorescent in situ hybridization.

The team further demonstrated that XIST activation led to upregulation of epigenetic markers, broad downregulation of messenger RNA expression on chromosome 21, and downregulation of specific genes on this chromosome.

“Our findings demonstrate atrial transcriptional correction of trisomic gene dosage and offer a scalable targeted platform for chromosomal therapy in DS and other aneuploidies,” the researchers reported.

They added: “The modified CRISPR method with XIST paves a rode for therapeutic treatment for DS.”

The post Down Syndrome Chromosomal Therapy Draws Closer appeared first on Inside Precision Medicine.

<![CDATA[Explore how sigma‑1 receptors shape ER–mitochondria signaling, calm neuroinflammation, and inspire therapies from fluvoxamine to dextromethorphan.]]>

AWS Launches Amazon Bio Discovery Agentic AI to Accelerate Drug Development

AWS has now unveiled Amazon Bio Discovery, an AI platform that grants researchers direct access to a broad library of biological foundation models that can be fine-tuned for specific use cases in drug discovery. Announced at the AWS Life Sciences Symposium at the Javits Center in New York, the platform is supported by an AI agent that can select models for research goals, and evaluate candidates for synthesis and testing to enable a rapid lab-in-the-loop experimentation cycle.  

While rising AI models show promise, they require coding skills and the ability to manage computing infrastructure. Additionally, diverse models face benchmarking challenges and moving candidates from computational design to physical synthesis remains a multi-step process. Given that data live in disconnected systems, scientists must manage multiple lab partners and manually coordinate timelines and execution.

Amazon Bio Discovery addresses these challenges with three capabilities: a benchmarked library of AI models and analysis packages, an AI agent that supports experimental lab, and integrated lab partners that test top antibody candidates and route results back to the researchers. This feedback loop improves the next round of design. 

“AI agents make powerful scientific capabilities accessible to all drug researchers, not just those with computational expertise,” said Rajiv Chopra, PhD, vice president of AWS Healthcare AI and Life Sciences.  

Currently, 19 of the top 20 global pharmaceutical companies use AWS to power research workloads. Amazon Bio Discovery will bring enterprise-grade scale, privacy, and security to researchers across pharmaceutical, biotech, and academic research organizations. MSK, Bayer, the Broad Institute, and Voyager Therapeutics are among early adopters of Amazon Bio Discovery. 

Among the Amazon Bio Discovery broad catalog includes open-source and commercial models from Apheris and Boltz. Biohub and Profluent are expected to join the platform. 

Amazon Bio Discovery enables scientists to fine-tune the model by feeding prior experimental data from their organization’s lab results into the application without complex training pipelines or custom code. In-house models can also easily be deployed and hosted within Amazon Bio Discovery.  

To support model selection, an antibody benchmark dataset is available to evaluate the likelihood of a drug candidate to have favorable biological properties, such as manufacturability and stability. 

Candidates selected for experimental validation can be directly sent to Amazon Bio Discovery’s integrated network of laboratory partners, including Twist Bioscience, Ginkgo Bioworks. A-Alpha Bio is also anticipated to join the network. 

The post AWS Launches Amazon Bio Discovery Agentic AI to Accelerate Drug Development appeared first on GEN – Genetic Engineering and Biotechnology News.

<![CDATA[A pharma expert and clinician shares perspectives on developing treatments.]]>

STAT+: FDA pressures drugmakers to report trial results

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Good morning. My colleague recently had a chance to talk with former senator Ben Sasse about his experience taking Revolution Medicines’ pancreatic cancer pill. Read on for what he said.

Ben Sasse thinks Rev Med drug ‘extended both quality and quantity of life’

Yesterday, we got highly promising results from a trial of Revolution Medicines’ pancreatic cancer pill, showing that patients on the medication lived nearly twice as long as those on chemotherapy.

Continue to STAT+ to read the full story…

From Colossal to Chickens: The Scientists Behind Neion Bio’s Biologics Platform

Twenty years ago, Sven Bocklandt, PhD, sought to create a hypoallergenic cat. He had the genetic engineering chops to do it, but the embryology was beyond his capabilities. At a small animal genetic engineering conference, known as TARC (Transgenic Animal Research Conference), held near Lake Tahoe, he met James Kehler, VMD, PhD, whose research at that time was to make transgenic and knockout cats as models of human disease.  

The two men bonded, agreed the hypoallergenic cat idea was “crazy enough,” and decided to move forward with it. They worked together, completely unfunded, for years—FedEx’ing samples back and forth as Bocklandt was on the west coast and Kehler on the east coast—trying to make their “garage cat” while each one worked different day jobs.  

Bocklandt, passionate about animal genome engineering, continued to develop different ideas for genome engineering in animals. Around the same time that he started sharing his ideas with scientists like George Church, PhD, a start-up focused on animal genome engineering was taking shape—Colossal Biosciences, co-founded by Church. Introductions were made, and Bocklandt joined in 2022 as species director to work on the dire wolf project. Kehler joined a short time later as VP. And everyone knows the rest of that story (there was no shortage of media coverage).  

The pair eventually succeeded with the cat project: his name is Archie, and he is, Kehler noted, only partially hypoallergenic. But the generation of Archie and the dire wolves may not be the successes of this story. The real success may be what Bocklandt and Kehler learned along the way—and what they are going to do next.  

Chickens as the next biologic factory

Neion Bio, co-founded by Dimi Kellari and Sam Levin, PhD, and located on the Rockefeller University campus on the east side of Manhattan, is aiming to re-engineer eggs to produce drugs in chickens. The team uses genetic engineering to integrate therapeutic proteins into native egg proteins, creating a new manufacturing platform for drugs that runs on grain and water.  

Bocklandt joined the team at Neion Bio as CSO after leaving Colossal in 2024; Kehler joined more recently, as head of avian sciences. 

When thinking about producing complex proteins, using the chicken “makes a lot of sense,” Bocklandt told GEN. Breeding and genetic engineering are all established in the chicken. And the vaccine industry has established an existing infrastructure to grow eggs under disease-free conditions. Purifying proteins out of an egg, Bocklandt added, is easier than purifying them out of a Chinese hamster ovary (CHO) culture (the traditional cell choice for drug production) because there are fewer host proteins.  

Sven Bocklandt, PhD [Marco Figueroa]

It makes “far more sense” than what we’re doing right now, Bocklandt noted, which is using CHO cells. “Everyone is doing that because everyone has been doing it that way,” he asserted.  

“The fact that we’re now seriously questioning whether CHO cells should remain the default manufacturing platform for biologics is long overdue,” noted Ola Wlodek, PhD, CEO of Constructive Bio. “Any credible new approach that breaks this decades-old lock-in is ultimately good for patients and for the field.”  

For Kehler, who did his graduate work in the lab of stem cell pioneer Hans Schöler, PhD, the chicken is a clear choice because it is the only species, besides the mouse, where the primordial germ cells have been used to transmit genetically modified gametes to the next generation.  

Mike McGrew, PhD, group leader at the Roslin Institute in the U.K., and an advisor to Neion Bio, demonstrated years ago that modifying chicken primordial germ cells is a reliable way of making gene-edited chickens. This background is comforting to Kehler, who noted that, “unlike at Colossal, where everything was bleeding edge, we are able to focus on a single species and capitalize on some pretty tried and true technology.”  

Drugs in eggs meet biomanufacturing reality

The lab space on the Rockefeller University campus can support research and even house chickens. But it cannot support the production of a drug. When asked about turning their egg-borne proteins into drugs, the company leans on the existing infrastructure that supports vaccines in specific pathogen free (SPF) eggs. The idea is that the egg whites will be frozen in giant batches and then processed in a CDMO.  

When asked about potential challenges, Bocklandt noted that, “technically, there’s not much to worry about. I have no concerns about Neion Bio being able to do what we want to do or what we need to do.”  

But there may be hurdles ahead. Rahul Dhanda, co-founder, president, and CEO of Syntis Bio, told GEN that “at the beginning, everything can look like it has infinite potential—it’s when you actually build and operate the system that the real challenges show up.”  

More specifically, Dhanda pointed out that biomanufacturing “ultimately comes down to reliable, consistent, and cost-efficient production.” Leveraging animal biology for drug manufacturing is exciting, he noted, “but scalability and cost are still open questions, especially at this early stage. Biological variability between animals and individual outputs, like eggs, introduces additional risk compared to more controlled cell-based systems,” Dhanda added.  

Wlodek agreed: “because egg-based production is inherently a biological supply chain, it will face avian flu risks, batch-to-batch variability from seasonal and flock effects, animal-welfare/regulatory overhead, and practical limits on how fast you can expand output compared with stainless-steel or single-use fermenters.” 

Microbial and yeast systems still “win decisively on GMP containment, land/water footprint,” she noted, and “the ability to go from a few liters to tens of thousands of liters in weeks rather than months.” 

Dhanda agreed that “getting it to work in principle is far different from getting it to work at scale, and that seems far off.” 

If these challenges can be addressed at scale, safely and humanely, Dhanda noted, the approach could deliver meaningful health benefits—”but there are still significant logistical and technical hurdles to work through.”  

Engineering the chicken genome

Creating dire wolves at Colossal started with deriving wolf cells, editing them, and cloning them back into a live animal. But cloning doesn’t exist in birds. To genetically engineer chickens, the Neion Bio team edits the germline, starting the process with a fertilized egg.  

Neion Bio
Neion Bio [Marco Figueroa]

The egg is incubated for 65 hours, at which point germ cells float in the blood because the ovaries and testes don’t exist yet. A microliter of the blood is removed, put into cell culture media, and the germ cells grow out. The transgene that codes for the therapeutic protein is inserted using CRISPR-Cas enzymes, in the coding region of a gene that codes for Ovalbumin—which makes up a bit over 50% of the egg white protein. This protein is made “on a massive scale” by the oviduct, the company noted.  

The genome is screened for correct integration and potential off-target edits. Once the clone is approved, several thousand cells are injected back into another embryo (also at 65 days old). After incubation, the egg hatches and becomes a chicken. 

Kanuma set the precedent—but not the scale

In 2015, the U.S. Food and Drug Administration approved Kanuma (sebelipase alfa) to treat Lysosomal Acid Lipase (LAL) deficiency, also known as Wolman disease. The drug, an enzyme replacement therapy, was the first treatment for patients with the rare disease and the first drug to be made in chickens. Kanuma is produced by Alexion Pharmaceuticals, which was acquired by AstraZeneca in 2021.  

This historical precedent may provide a proof of concept for Neion Bio. That said, “the scale required for Kanuma is very different from what would be needed for large biosimilars,” explained Wlodek.  

An Odyssean journey

For both Bocklandt and Kehler, the move to Neion Bio feels like their careers are coming full circle. When Bocklandt first left Colossal, he was not sure how he would surpass that level of excitement. But the move came at an interesting time for him; the call to join Neion Bio came just weeks after he learned that his sister had been diagnosed with leukemia.  

He thought, “Well, maybe this is not such a bad use of my skills.”  

Earlier in his career, he didn’t think that he had anything special to add to a field like cancer research. But now Bocklandt sees it differently: throughout his career, he has pushed the state-of-the-art of genetic engineering. Now, he said, “I bring something to the field. And the fact that I can do my passion, animal genetic engineering, and apply that to make drugs better, cheaper, and more accessible, is really exciting.”  

As for Kehler, Neion’s goal was his goal all along. He went to the University of Pennsylvania to make better animal models to test drugs for humans. “It never really dawned on me that we could use animals to make the drugs for humans. But taking everything I know about stem cell biology, germ cell biology, and gene editing, and bringing that to bear to make what should be a disruptive, transformational approach to making drugs—it feels like the culmination of my career.” 

Neion (pronounced Neon) Bio is named after the birthplace of Odysseus; Mount Neion is a mountain mentioned in Homer’s The Odyssey as a landmark on Ithaca—Odysseus’ island home. As described by the company, the name is a testament to the shared qualities between the Greek hero and the company’s goals: relying on intelligence and resourcefulness over strength. And yes, Odysseus was successful in his return home to reclaim his throne. But it was a bittersweet success given the enormous cost and hardship.

Neion Bio’s name may mirror the resilience and ingenuity required to undertake the journey, but time will tell how long the similarities in the namesake are shared between the two.

The post From Colossal to Chickens: The Scientists Behind Neion Bio’s Biologics Platform appeared first on GEN – Genetic Engineering and Biotechnology News.

<![CDATA[Psychiatry training must catch up with chatbot literacy, intake, safety, ethics, and supervised AI integration.]]>

STAT+: Hospitals offer chatbots to fight off ChatGPT

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Good morning health tech readers!

Super interested in the list of companies that have been accepted into Medicare’s ACCESS model, the technology-enabled chronic care experiment. 

Continue to STAT+ to read the full story…