Nature Biotechnology, Published online: 15 May 2026; doi:10.1038/s41587-026-03129-w
ΨDNA guides are used with Cas12 for precise, programmable targeting of cellular RNA.
DNA‑Guided CRISPR Suggests a New Direction for RNA Editing
CRISPR’s rise from obscure bacterial defense system to molecular scalpel has always hinged on one small component: the guide RNA. For years, that guide RNA—meticulously designed, modified, and optimized in countless labs—has been treated as an immutable feature of the system. CRISPR cuts where the RNA tells it to cut. That’s the central dogma of the system.
But a new approach suggests the system is more flexible than anyone expected. The study, published in Nature Biotechnology, is titled “DNA-guided CRISPR–Cas12 for cellular RNA targeting.”
Researchers at the University of Florida (UF) have developed the first CRISPR system that uses DNA, rather than RNA, to direct Cas enzymes to RNA targets. The platform, called ΨDNA, reprograms Cas12 nucleases to recognize and act on RNA using a DNA-based guide scaffold. The result is a fundamentally different way of controlling RNA inside cells—one “that extends Cas12 systems beyond genome editing and diagnostics to enable precise, programmable control of cellular transcriptomes and their epitranscriptomic marks,” according to the authors.
The concept is rooted in a simple biological distinction. DNA stores the cell’s long-term instructions, but RNA carries the working copies. “Those RNA copies are like Xerox copies of the original manual, and sometimes those copies have errors,” said Piyush Jain, PhD, associate professor of chemical engineering at UF and lead author of the study. Errors in those working copies can drive disease, and targeting RNA offers a way to intervene without altering the underlying genome. But RNA‑guided CRISPR systems, such as Cas13, can suffer from instability and off‑target effects. “Existing RNA-targeting CRISPR systems rely on RNA guides to find their targets,” Jain said. “While effective, they can sometimes affect unintended molecules… They can also be costly and less stable.”
ΨDNA takes a different approach. The team engineered a DNA guide that mimics the crRNA scaffold in reverse orientation, enabling AsCas12a and Cas12i1 to bind RNA and trigger strong single‑stranded DNA trans‑cleavage. As the abstract describes, “ΨDNA… enables RNA targeting by Cas12 nucleases… including 100% accurate hepatitis C virus RNA detection in clinical samples.” In human cell lines, ΨDNA achieved 70–95% knockdown of endogenous RNA transcripts, driven by mechanisms such as ribosome stalling and RNase H1 recruitment.
Jain sees the work as a conceptual shift for CRISPR. “The most meaningful advance is that we show CRISPR‑Cas12 can be reprogrammed to target RNA using a DNA guide rather than an RNA guide,” he told GEN. “That is a real conceptual shift for the field.” Until now, RNA targeting has been dominated by RNA‑guided systems. ΨDNA demonstrates that Cas12 enzymes—traditionally DNA editors—can be redirected toward RNA “while preserving strong specificity and enabling multiple functions, including RNA detection for developing diagnostics, intracellular knockdown, multiplex targeting, dual DNA and RNA targeting, and effector fusion strategies for RNA modification and potential therapeutic strategies.”
The discovery emerged from a structural puzzle. Simply swapping RNA bases for DNA bases does not work; Cas12 enzymes are thought to be tightly dependent on RNA scaffolds. “Several groups have tried to achieve DNA-guided CRISPR/Cas, but simply converting RNA bases to DNA bases doesn’t work,” Jain said. The breakthrough came from engineering a 3′ DNA handle that recreated the crRNA scaffold. Mutational screening revealed that a stem‑loop architecture was essential for activity, and recent cryo‑EM structures—solved in collaboration with David Taylor’s group at UT Austin—showed that AsCas12a has more structural flexibility than expected, allowing it to accommodate a DNA guide bound to an RNA target.
What surprised the team most was how robust the system proved to be. “It was especially exciting to see that this was not just an in vitro curiosity,” Jain said. ΨDNA worked in clinical RNA detection, achieving 100% accuracy on hepatitis C virus samples, and functioned inside cells with lower off‑target effects than Cas13d.
The platform’s modularity may be its most powerful feature. ΨDNA can be fused to RNase H1 for targeted RNA degradation or to METTL3 for epitranscriptomic editing. And because crRNA and ΨDNA can be codelivered, a single Cas12a enzyme can operate in two modes at once. “A single Cas12a effector can simultaneously edit DNA and regulate RNA,” Jain said. “This work starts to blur that boundary.”
Looking ahead, the team is expanding both the mechanistic and translational sides of the platform. They are refining guide design rules, dissecting how ΨDNA‑guided Cas12 triggers knockdown, and exploring applications in diagnostics, multiplex RNA regulation, and ex vivo therapeutic settings. One emerging direction involves using the technology to repair donor organs before transplantation.
More broadly, DNA guides offer practical advantages. They are easier to synthesize, more stable, and potentially more scalable than RNA guides. That combination could make ΨDNA a versatile platform for basic research, diagnostics, and future therapeutic engineering.
After decades of CRISPR research built around RNA‑guided systems, ΨDNA introduces a new way to direct one of biology’s most powerful tools. As Jain put it, “At its core, this is about giving us better control—not just rewriting the instruction manual but also precisely managing how those instructions are used.”
The post DNA‑Guided CRISPR Suggests a New Direction for RNA Editing appeared first on GEN – Genetic Engineering and Biotechnology News.
The world is on track to miss its health targets
Every year the World Health Organization publishes a global health statistics report. It features the numbers behind world health trends and, importantly, assesses whether we’re on track to reach ambitious goals set in 2015. It’s a bit like a health grade.
The 2026 report was published on Wednesday. And the results aren’t looking brilliant. While we are seeing some improvements, they are uneven, and they’re far too slow.
The targets themselves are part of the United Nations’ Sustainable Development Goals, a sprawling and ambitious plan focused on improving life around the world. The 17 goals were set to tackle poverty and climate change and to boost education, gender equality, health, and well-being, among many other quality of life issues. Those targets were meant to be met by 2030.
Perhaps they were a little too ambitious. Here are the numbers and statistics that stood out to me on this year’s world health report card.
1.3 million new cases of HIV in 2024
Before the SDGs, there were the Millennium Development Goals. One MDG target was to halt and reverse the spread of HIV—and that target was exceeded by 2015. Back then, we were considered on track to “end the AIDS epidemic by 2030.”
How depressing, then, to see that in 2024 there were an estimated 1.3 million new cases of HIV. That’s 40% lower than the figure from 2010. But it’s still 1.3 million additional people with HIV. The SDG target is to reduce HIV incidence by 90% by 2030—we’re not likely to meet it.
10.7 million new cases of TB
The picture is even bleaker for tuberculosis, which ranks 10th on the WHO’s list of top global causes of death. The goal was to reduce cases by 80% between 2015 and 2030. So far, cases have only fallen by a measly 12%. And when you break the change down by region, the Americas saw an increase of 13%
An 8.5% rise in malaria cases
And then there’s malaria, the mosquito-borne disease with a 7% fatality rate. The European region has been free of malaria since 2015, but the disease is a significant concern in many countries in the Global South, particularly in Africa. The goal was to lower rates by 90% between 2015 and 2030. In 2024, there were an estimated 282 million cases of malaria globally—representing an 8.5% increase in incidence rates.
Antimalarial drug resistance is a major challenge here—forms of the malaria virus that are resistant to drugs have been confirmed or suspected in eight countries in Africa, according to a separate WHO report. Mosquitoes that are resistant to commonly used insecticides are present in nine African countries. And climate change, which can alter mosquito habitats, may be making things worse.
42.8 million children are wasting
We’re not meeting child health targets, either. Take malnutrition, for example. As of 2024, the global prevalence of wasting in children was 6.6%—that’s a staggering 42.8 million children who are literally wasting away because of a lack of adequate food. On the other end of the spectrum, 5.5% of children are now considered overweight. Both figures were meant to be below 5% by 2030, which now seems unlikely.
Vaccination rates are dropping in the Americas
Progress in improving childhood vaccination coverage has stalled. Globally, an estimated 76% of children are getting their second dose of a measles vaccine—a figure far below the the approximately 95% needed to prevent outbreaks. The Americas currently has lower rates of vaccine coverage for three of the four “core” vaccines than it did in 2015.
This is partly due to a lack of investment, says Goodarz Danaei, an epidemiologist at the Harvard T.H. Chan School of Public Health. “But now we have a misinformation campaign going around vaccines that makes it worse,” he adds.
The covid-19 pandemic didn’t exactly help, either. The impact on health services led to millions of children missing out on routine vaccinations.
22.1 million pandemic-related deaths
And of course the pandemic affected progress toward health goals in more direct ways: 7 million people died of covid-19. The WHO report estimates that, for each of these, there were an additional two “excess” deaths related to the pandemic, due to disruptions in health care, for example. That puts the total figure at 22.1 million pandemic-related deaths.
A woman dies every two minutes from “maternal causes”
Maternal mortality rates fell by about 40% between 2020 and 2023. But today’s rate equates to 712 maternal deaths every single day. That’s one every two minutes. The WHO report notes that we’d have to reduce the mortality rate by almost 15% per year in order to meet the 2030 target. This seems incredibly unlikely, particularly given the recent decimation of US funding for global aid programs, which is expected to result in thousands of additional maternal deaths.
Progress has also slowed in reducing the risk of death from noninfectious diseases like cancer, diabetes and cardiovascular disease. “Overall, neither the world nor any WHO region is currently on track to meet the 2030 SDG target,” the report states.
2.1 billion people struggle to afford health care
Despite plans to make health care more affordable, a significant chunk of the population is being pushed into poverty by health-care costs. In 2022, 2.1 billion people faced financial hardship due to health spending—and 1.6 billion of them were living in or had been pushed into poverty.
Across the board, there have been some important improvements in global health. But the achievements have not gone far enough. “The good news is that there is progress,” says Danaei. “But as always, the glass is half empty.”
This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.
Implantable Living Materials Contain Infection-Sensing Bacteria That Release Therapeutics
Overcoming a major hurdle in the use of microbes as medicine, researchers at Harvard’s Wyss Institute and John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed an “implantable living materials” (ILMs) platform comprising encapsulated infection-sensing bacteria that can release therapeutic molecules on demand but are kept physically separated from the surrounding tissue.
Wyss Founding Core Faculty member David Mooney, PhD, and colleagues encapsulated a genetically engineered, therapeutic strain of E. coli bacteria within a biomaterial made from a hydrogel that was specifically designed to regulate bacterial growth and resist mechanical stresses, such as those present at physically active sites in the body, demonstrating that the bacteria could be confined for over six months.
To evaluate the material’s clinical potential, the researchers transformed the ILM into an active therapeutic system by engineering the bacteria to detect chemical signals from Pseudomonas aeruginosa, a common cause of implant-related infections. In response to the pathogen, the engineered bacteria autonomously self-destructed to release an antibacterial protein that killed the P. aeruginosa. In a mouse model of joint infection, the system successfully reduced bacterial burden, demonstrating the potential of durable, programmable ILM-based therapeutics for long-term disease treatment. The researchers suggest that their development represents a shift from passive drug depots to autonomous, responsive—and living—therapeutic systems.
“With this new strategy combining both an engineered material with designed mechanical features and genetically engineered microbes that produce therapeutic payloads on demand, we provide a generalizable framework for deploying future microbial medicines,” said Mooney. “The precision, safety, and therapeutic durability afforded by this ILM strategy could be a potential solution for treating a wider range of diseases and infections, enabling therapeutic efficacies that might surpass those of other drug delivery strategies.”
Mooney, the Robert P. Pinkas Professor of Bioengineering at SEAS, is co-senior and corresponding author of the team’s published paper in Science, titled “Implantable living materials autonomously deliver therapeutics using contained engineered bacteria,” in which the authors concluded that their collective results “… establish ILMs as a foundation for deploying microbial medicines in vivo as autonomous therapeutic depots across diverse disease settings.”
Patient recovery from many debilitating conditions and diseases could be sped up significantly and be more effective if drugs and therapeutic molecules were delivered right to where they are needed in the body, over the entire regenerative process, and in doses finely tuned to therapeutic needs. An intriguing way to achieve this is the use of implantable, synthetically engineered, living cells that can sense injury or disease-associated conditions in their environment and flexibly respond by producing the right amount of a therapeutic molecule.
“Synthetically engineered cells are emerging as living therapeutic modalities, capable of sensing physiological conditions and producing bioactive payloads in vivo,” the authors wrote. Unlike conventional drugs, these “living therapeutics” can sustain themselves in vivo and survive in many biological environments, including tumors, inflamed tissues, infected tissues, and even within human cells.
Bacteria are particularly attractive because they can be genetically programmed to release therapeutic molecules in response to specific biological signals. Bacteria can thrive in harsh physiological environments within the body, such as within infected or inflamed tissues, tissues undergoing mechanical movements, and tumors.
Some such microbial therapies have even advanced into clinical trials to treat certain cancers, metabolic disorders, and the progression of kidney stones. However, thus far, such trials have failed, and microbes are feared to also pose significant safety risks because they cannot be contained at specific sites in the body. “… controlling microbial off-target effects remains a key safety consideration because dissemination and associated toxicity have been reported across multiple clinical contexts,” the authors continued.
Previous implantable biomaterial systems, such as hydrogels and capsule-like enclosures, have shown some success in confining microbes, but only for short periods—typically no more than two weeks. “Implantable hydrogels offer a physical strategy to confine therapeutic cells at target sites,” the investigators commented. “Such living materials hold promise as localized drug depots with the capacity to dynamically respond to diseased environments … In this work, we present an implantable material that encapsulates and confines bacteria, wherein synthetically engineered microbes produce therapeutic payloads from within.”
First author Tesuhiro Harimoto, PhD, who spearheaded the project as a postdoctoral fellow in Mooney’s group, explained further, “In the beginning, we asked the seemingly simple question, what if we could design a material that safely encapsulates drug-delivering bacteria inside and allows therapeutic drugs to pass through to where they are needed.” Although scientists have extensively studied how physical parameters of synthetic materials change with tweaks made to their composition and chemical connections, “this was a big ask since the encapsulating material had to reconcile two often contradictory features: it needed to be sufficiently ‘stiff’ so that bacteria pushing against it from the inside can’t break it apart, and sufficiently ‘tough’ to provide a enclosure that protects against external physical stresses in mechanically active tissues.”
![Graphical abstract: "Implantable living materials autonomously deliver therapeutics using contained engineered bacteria" [Tetsuhiro Harimoto]](https://www.genengnews.com/wp-content/uploads/2026/05/low-res-300x282.jpeg)
An expanding bacterial colony can exert pressures that are multiple orders of magnitude higher than those produced by mammalian cells. Also, the type of stresses produced by the body’s various mechanical forces, such as, for example, generated by tension in muscles or compression on joints, can fatigue a material over time and disrupt it from the outside. However, introducing too much stiffness can often make a material too brittle, which means that cracks can quickly propagate through it; and a high toughness, which, in principle, allows a material to resist fracturing, often makes it soft. “We hypothesized that fulfilling two key criteria for a material enables robust and durable containment of therapeutic bacteria: (i) resistance to the internal forces generated by proliferating bacteria and (ii) mechanical toughness sufficient to withstand deformation from surrounding tissues,” the team wrote.
To realize ILMs, the team started with polyvinyl alcohol (PVA), which is already used clinically, and processed it to form nanoscale interactive crystalline domains. The resulting scaffolds are simultaneously highly stiff and tough. “Finding out how to fabricate optimal hydrogels from PVA that are crosslinked through dense crystalline domains, and how to do this in a way that keeps the enclosed bacteria alive and active, was a big part of our study,” said Harimoto. The researchers included the bacteria in their fabrication process within tiny droplets of gelatin that protected them against desiccation and selective chemical manipulations.
This strategy allowed them to fabricate an ideally stiff and tough material scaffold around the bacteria, using a combination of tolerable freeze-thaw cycles, salt conditions, and chemical treatment times. Late in the process, via a slight shift in temperature, the gelatin microgel could be dissolved to create internal voids for the bacteria to thrive in. Due to the tiny pore sizes within the PVA material, the bacteria remain constrained while the soluble molecules they produce can travel to other sites in the body.
The resulting ILM safely contained the bacteria over extended time intervals of up to six months and was resistant to repeated mechanical stresses. “We developed a hydrogel scaffold with dual mechanical features: high stiffness to regulate bacterial proliferation and high toughness to resist material fracture under physiological stress,” the investigators stated. “This design achieved complete bacterial containment for six months and withstood multiple forms of mechanical loading that otherwise caused catastrophic material failure.”
To provide proof-of-concept for ILMs, the team focused on the infection of implanted periprosthetic devices designed to treat fractures or bone loss around existing artificial joint replacements by pathogenic P. aeruginosa strains. Many treatments with periprosthetic devices fail due to infection, which goes along with inflammation and the spread of antibiotic resistance. “We evaluated the use of ILMs for periprosthetic joint infection in vivo,” they wrote. This model was designed to capture early postimplantation infection during which most infections arise in clinical settings.”
To effectively treat this and other types of infection, the therapy-delivering bacteria within the ILM needed to be genetically engineered to function as a drug depot with autonomous “sense-and-respond” capabilities. To achieve this, the team installed a synthetic gene circuit in the E. coli strain that enabled the bacteria to sense a small diffusible metabolite produced by P. aeruginosa, known as N-acyl homoserine lactone (AHL), and, in response, activate a self-destruction gene to trigger cell lysis. The self-destruction process, triggered in a fraction of ILM bacteria, resulted in release from the ILM of a synthetic P. aeruginosa-killing protein called chimeric pyocin (ChPy) that the bacteria produce continuously. ChPy is toxic to P. aeruginosa, erasing the pathogen in the local ILM environment.
“When we tethered a therapeutic ILM to a stainless steel periprosthetic device that was infected with a pathogenic P. aeruginosa strain isolated from a patient’s wound and implanted next to the femur bone of mice, it significantly reduced the pathogen burden while safely containing its engineered bacteria over a three-day treatment course,” said Harimoto. “In contrast, in mice that we treated with a non-therapeutic control ILM that did not produce ChPy, the numbers of P. aeruginosa bacteria continued to rise over the same time interval. This demonstrated the ability of therapeutic ILMs to autonomously sense and treat periprosthetic infection in vivo.”
The researchers think that specifically engineered ILMs as a novel class of therapeutics with excellent safety features and locally targeted drug release capabilities have broad potential, ranging from tissue regeneration to immune modulation in a variety of disease settings. A patent application describing the use of ILMs for drug delivery has been filed.
In their paper, the authors wrote in summary, “ILMs are distinct from other therapeutic modalities, such as drug-loaded depots and vaccines. By directly sensing pathogen-derived signals and locally releasing antimicrobial payloads, ILMs enable rapid, antigen-independent intervention at the implant site. This localized, autonomous mode of action is well-suited for periprosthetic joint infection, where early intervention is critical.” Their collective results, the team suggests, “…establish ILMs as a foundation for deploying microbial medicines in vivo as autonomous therapeutic depots across diverse disease settings.”
In a related perspective, Kaige Chen, PhD, and Quanyin Hu, PhD, at the School of Pharmacy, University of Wisconsin–Madison, acknowledge that further work will be needed to determine whether contained living therapeutics can function in vivo over long periods. Nevertheless, they said, “The study of Harimoto et al. addresses a central obstacle to deploying living therapeutics—keeping bacteria physically separated from the surrounding tissue. Chen and Hu further note that the in vivo findings in the artificial joint mouse model “… could advance living therapeutics from short-lived proof-of-concept systems to durable, programmable medicines.”
The post Implantable Living Materials Contain Infection-Sensing Bacteria That Release Therapeutics appeared first on GEN – Genetic Engineering and Biotechnology News.
Molecular Anchors Help Tumor Therapies Stay Longer on Cancer Cells
For cancer therapies to work, they need to stay in proximity to the target diseased tissues for long enough. To help with that challenge, a group of scientists, led by a team at University of California, San Francisco (UCSF), have developed a drug carrier that physically anchors itself to cancer cell membrane, which helps to improve drug retention and effectiveness. Full details are published in a new ACS Central Science paper titled “A Prodrug Strategy to Conditionally Trap Therapeutic Payloads for Improved Tumor Retention.”
“Retaining drugs within tumors is an often-overlooked dimension of drug development that nevertheless greatly impacts the therapeutic window and outcomes,” said Michael Evans, PhD, a professor in the department of radiology and biomedical imaging at UCSF and a corresponding author on the study. In fact, approaches that deliver cancer therapeutics to tumors but lack dedicated mechanisms to ensure tumor retention often lose efficacy within a few days of drug administration.
Previously, Evans and others designed drug delivery systems called restricted interaction peptides or RIPs that can deliver diverse therapeutic cargos including cytotoxins and radioisotopes. They work by changing shape when processed by disease-associated enzymes. These allow them to embed in cell membranes, tethering their drug payloads in place, promoting cellular uptake and improving effectiveness. Building on that work, the scientists engineered RIPs to interact with fibroblast activation protein, a serine protease that is prevalent in solid tumors and fibrosis.
Imaging studies of cancer cell cultures showed that a fluorescently tagged RIP was rapidly taken up by the cells. Then when the scientists attached an anticancer drug, monomethyl auristatin E or MMAE, to the RIP, they found that the drug-peptide combination was as effective in killing cancer cells as the drug alone. Furthermore, when the drug-peptide combination was injected into mice with human cancers, it selectively targeted tumor tissue and was more effective at shrinking tumors than the unmodified drug with fewer side effects. The scientists observed similar results when they attached RIPs to radioactive copper isotopes which are commonly used in nuclear imaging and radiotherapy.
The scientists expect to initiate Phase I clinical imaging studies of the RIP-radioactive copper isotope pairing in human cancer patients later in 2026 in collaboration with a company that is developing RIPs into therapeutics.
The post Molecular Anchors Help Tumor Therapies Stay Longer on Cancer Cells appeared first on GEN – Genetic Engineering and Biotechnology News.
The Download: deepfake porn’s stolen bodies and AI sharing private numbers
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
The shock of seeing your body used in deepfake porn
When Jennifer got a research job in 2023, she ran her new professional headshot through a facial recognition program. She wanted to see whether it would pull up the porn videos she’d made more than a decade earlier. It did, but it also surfaced something she’d never seen before: one of her old videos, now featuring someone else’s face on her body.
Conversations about sexualized deepfakes usually focus on the people whose faces are inserted into explicit content without consent. But another group often gets ignored: the people whose bodies those faces are attached to.
Adult content creators say AI systems are training on their work, cloning their likenesses, and generating explicit content they never agreed to make, all with little legal protection or control. Read the full story on the threat to their rights, livelihoods, and ownership of their own bodies.
—Jessica Klein
This story is part of our The Big Story series, the home for MIT Technology Review’s most important, ambitious reporting. You can read the rest here.
AI chatbots are giving out people’s real phone numbers
Generative AI is exposing people’s personal contact information—and there’s no easy way to stop it.
A software developer started receiving WhatsApp messages asking for help after Gemini surfaced his number. A university researcher got the chatbot to reveal a colleague’s private cell number. A Reddit user says Gemini sent a stream of callers looking for lawyers to his phone.
Experts believe these privacy lapses stem from personally identifiable information in AI training data. Chatbots may now be making that information dramatically easier to find.
Find out why these breaches are growing—and why there’s little that victims can do to stop them.
—Eileen Guo
The Tesla Semi could be a big deal for electric trucking
Nearly a decade after Elon Musk first unveiled the Tesla Semi, the electric truck is finally rolling off the production line. It could be a breakout moment for battery-powered freight.
Semitrucks produce an outsized share of road transport pollution, while electric alternatives have struggled with high prices, limited range, and charging challenges. Tesla is betting the Semi can overcome those problems. The truck reportedly travels up to 480 miles on a single charge and costs far less than many competing electric models.
Here’s how the Tesla Semi could give electric trucking a vital boost.
—Casey Crownhart
This article is from The Spark, MIT Technology Review’s weekly climate newsletter. To receive it in your inbox every Wednesday, sign up here.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 The US has approved Nvidia chip sales to 10 Chinese firms
Alibaba, Tencent, and ByteDance are among those cleared to buy H200 chips. (Reuters $)
+ The US will receive 25% of the revenue from the sales. (Engadget)
+ But Beijing wants domestic firms to prioritize homegrown chips. (Nikkei Asia)
+ Nvidia CEO Jensen Huang is in China with a White House delegation. (CNBC)
2 Beijing’s push for AI independence is weakening US leverage
It’s allowing China to resist pressure during the Beijing talks. (NYT $)
+ The country has made a big bet on open-source. (MIT Technology Review)
+ Here’s what’s at stake for tech at the Trump-Xi meeting. (Rest of World)
3 AI is “rotting the brains” of developers
They’re losing their previous abilities to do their jobs. (404 Media)
+ A populist backlash is building against AI. (MIT Technology Review)
+ It’s time to reset our expectations about AI. (MIT Technology Review)
4 Sam Altman has over $2 billion in companies that have dealt with OpenAI
The ties have triggered accusations of conflicts of interest. (The Times $)
+ The GOP is scrutinizing Altman’s business dealings. (WSJ $)
5 Andreessen Horowitz has become the top political donor in the US
A16z contributed $115.5 million to the midterm elections. (NYT)
+ AI lobbying has reached a fever pitch. (NYT $)
6 Microsoft feared being too dependent on OpenAI
CEO Satya Nadella was worried about OpenAI supplanting his company. (CNBC)
+ Microsoft is eyeing startup deals for life after OpenAI. (Reuters $)
7 AI systems are forecasting wars and regime collapse
One estimates a 20% chance of regime change in Iran by 2026. (Economist $)
+ AI has turned the Iran conflict into theater. (MIT Technology Review)
8 Anthropic says a model behaved badly due to training on dystopian sci-fi
Training on more positive stories could help. (Ars Technica)
9 Data centers now consume 6% of the electricity in the US and UK
AI’s global energy consumption is up 15% globally in two years. (Guardian)
10 NASA has rescued Curiosity after its drill got stuck on Mars
The agency has just revealed how it freed the rover. (Wired $)
Quote of the day
“Musk loves to be glazed, and this person is the doughnut factory.”
—Joan Donovan, assistant professor of journalism and emerging media studies at Boston University, tells the Washington Post how Elon Musk has consistently amplified one anonymous X account.
One More Thing
YOSHI SODEOKA
Inside the messy ethics of making war with machines
In a near-future war—one that might begin tomorrow—a sniper’s computer vision system flags a potential target. Just over the horizon, a chatbot advises a commander to order an artillery strike.
In both cases, an AI system recommends pulling the trigger while a human still has the final say. But how much of the decision is really theirs? When, if ever, is it ethical for that decision to kill? And who’s to blame when something goes wrong?
This is how AI is reshaping decision-making on the battlefield.
—Arthur Holland Michel
We can still have nice things
A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)
+ The secrets behind how Shazam works have been revealed.
+ For the first time in a decade, a rare “Cloud Jaguar” was caught on camera.
+ Explore our galaxy from your screen at this year’s Milky Way Photographer of the Year collection.
+ If you want a game over with style, a funeral company is offering Mario, Luigi, Peach, and even Yoshi-branded coffins.
STAT+: CREATE Medicines, a biotech company developing CAR-T therapies, raises $122 million
CREATE Medicines has a new name, an expanded pipeline, and now fresh funding to propel the company’s first CAR-T candidates through human trials.
Up until last year, CREATE was known as Myeloid Therapeutics. The startup was cofounded by noted writer and oncologist Siddhartha Mukherjee to develop better CAR-T therapies using a type of immune agent called myeloid cells, ideally to better attack solid tumors. The company rebranded last fall and, like many other oncology CAR-T companies, expanded into autoimmune disease research.
Now, CREATE has raised another $122 million from Newpath Partners, ARCH Venture Partners, Hatteras Venture Partners, and others, the biotech told STAT exclusively.
STAT+: ‘No drama’ Diamantas should serve biotech well as acting FDA chief
This is the online version of Adam’s Biotech Scorecard, a subscriber-only newsletter. STAT+ subscribers can sign up here to get it delivered to their inbox.
Kyle Diamantas, the acting commissioner of the Food and Drug Administration — newly installed following Marty Makary’s resignation — is expected to be a drama-free, stabilizing caretaker at the top of the agency.
Leadership turnover is always going to cause some angst, but based on what I’m hearing, biotech and the investors who track the sector have little to fear from Diamantas. He is stepping into the new role after serving as the FDA’s top food regulator.
BMS, Hengrui Pharma Partner on 13 Programs in Up-to-$15.2B Collaboration
Bristol Myers Squibb (BMS) will partner with Hengrui Pharma to co-develop 13 early-stage programs in oncology, hematology, and immunology, the companies said today, through a collaboration that could generate more than $15.2 billion for the Chinese drug developer.
BMS and Hengrui have inked global strategic collaboration and license agreements covering the 13 candidates—consisting of four oncology/hematology assets from Hengrui, four immunology assets from BMS, and five “innovative” assets to be jointly discovered and developed by both companies.
The companies said their collaboration is intended to combine BMS’ research and discovery strengths, global clinical development capabilities, regulatory expertise, and commercial scale with Hengrui’s discovery engine, platform technologies, and efficient early-stage development expertise.
To that end, Hengrui has agreed to fully oversee early clinical development in order to accelerate clinical proof of concept for these programs. Hengrui has the option to co-develop select assets and the potential to conduct certain commercialization activities globally with BMS.
“By leveraging Hengrui’s growing R&D capabilities and proven efficiency in discovering and advancing innovative therapies, we are poised to advance the best of both pipelines,” Frank Jiang, MD, PhD, Hengrui’s executive vice president and chief strategy officer, said in a statement. “It also reflects Hengrui’s continued commitment to strengthen our global presence.
BMS will obtain exclusive worldwide rights to the Hengrui‑originated candidates outside China, Hong Kong Special Administrative Region (SAR), and Macau SAR—Hengrui’s territory of operation—while Hengrui will gain exclusive rights to the BMS‑originated assets within those areas, with BMS retaining rights for the rest of the world.
$950M over two years
BMS has agreed to pay Hengrui up to $950 million over two years, to consist of a $600 million upfront payment, a $175 million first anniversary payment, and a second contingent anniversary payment of $175 million in 2028.
The approximately $15.2 billion value of the collaboration includes exercising available options for the joint discovery programs and achieving development, regulatory, and commercial milestones for all programs. Hengrui also is eligible to receive tiered royalties on net sales of products commercialized outside its territory.
The collaboration deal is expected to close in the third quarter, subject to review under the Hart‑Scott‑Rodino Antitrust Improvements Act and other customary closing conditions.
“This strategic collaboration reflects our commitment to advancing innovative science while maintaining a disciplined approach to portfolio management,” stated Robert Plenge, MD, PhD, BMS executive vice president and chief research officer. “By leveraging complementary capabilities across geographies, we aim to accelerate early clinical learning and make informed decisions that support driving top tier growth in the next decade and, ultimately, our mission to deliver medicines that help patients prevail over serious diseases.”
Recouping ‘patent cliff’ losses
Behind that focus on top-tier growth for BMS, as with other pharma giants, is a quest to recoup the billions of dollars in sales it stands to lose as aging blockbuster drugs head for the proverbial “patent cliff” by losing exclusivity in the U.S. and other key markets.
Of the Top 20 Drugs Heading for the Patent Cliff through 2029—the subject of a GEN A-List last November—BMS had three marketed treatments: The cancer drug Revlimid® (lenalidomide), indicated for forms of multiple myeloma, myelodysplastic syndromes, and three forms of lymphoma, which lost U.S. exclusivity in January; and two drugs set to lose exclusivity in 2028: the cancer immunotherapy Opdivo® (nivolumab), and the factor Xa-inhibiting blood thinner Eliquis® (apixaban).
Eliquis generated $14.443 billion in product revenue last year plus another $4.137 billion in the first quarter. Opdivo made $10.049 billion in 2025 plus $2.146 billion in Q1, while Revlimid racked up $2.951 billion and $349 million.
BMS has laid groundwork for rebuilding its pipeline over the past year through a series of collaborations and acquisitions with companies that include:
- Janux Therapeutics: An up-to-$850 million partnership announced in January to co-develop a tumor-activated therapeutic targeting an undisclosed “validated solid tumor antigen expressed across several human cancer types.” ($50 million upfront).
- Harbour BioMed: An up-to $1.125 billion partnership with the Chinese biopharma—owned to discover and develop next-generation multi-specific antibodies ($90 million upfront), announced in December 2025.
- Orbital Therapeutics: A $1.5 billion cash acquisition of the developer of RNA therapies designed to treat disease by reprogramming cells in vivo, announced in October 2025.
- 2seventy bio: An approximately $286 million buyout of its partner in developing the blockbuster multiple myeloma drug Abecma® (idecabtagene vicleucel), announced in March 2025. Abecma made $427 million last year. The drug’s sales are no longer reported individually but within BMS’ “Growth portfolio” that garnered $581 million in Q1 2026.
Five castoffs
BMS also outlicensed five pipeline assets to Beeline Medicines, an autoimmune and inflammatory drug developer formed in April with a $300 million Series A financing from Bain Capital. Beeline’s pipeline of BMS castoffs includes afimetoran, being developed for both cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE), BMS-986326 (atopic dermatitis, CLE, and SLE); lomedeucitinib (formerly BMS-986322, plaque psoriasis), and two IND-stage next-generation biologics for unspecified diseases that target the IL-18 and IL-10 pathways.
Hengrui last September outlicensed its cardiac myosin inhibitor RS-1893 to Braveheart Bio ($65 million upfront, up to $1.013 billion in milestones); and two months earlier inked an up to $12.5 billion ($500 million upfront) partnership with GlaxoSmithKline (GSK) to develop to develop chronic obstructive pulmonary disease (COPD) candidate HRS-9821 and 11 additional programs across respiratory, immunology and inflammation, as well as oncology indications.
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ASGCT President Terry Flotte Touts Rare Disease Initiatives as His Term Ends
President of the American Society of Gene and Cell Therapy (ASGCT), Terry Flotte, MD, is excited to host this year’s conference in his own backyard. It will be a short drive east on the Mass Turnpike from his office at UMass Chan Medical School in Worcester to the Menino Convention and Exhibition Center in Boston’s Seaport district. Flotte is hopeful that the 2026 conference will draw the largest attendance in the meeting’s history. His tenure as president ends this week on the last day of the conference, May 15.
In the run-up to this year’s conference, GEN spoke with Flotte, who is also Editor in Chief of GEN’s sister journal Human Gene Therapy, about the central themes and most anticipated sessions at this year’s conference. “I have a full dance card, let me tell you,” Flotte joked. The conference will highlight several themes of Flotte’s productive tenure.
(This interview has been edited for length and clarity.)
GEN: Terry, what’s the theme of this year’s ASGCT conference?
Terry Flotte: We’re working very hard on access for rare and ultra-rare conditions and have been for some time. You’ll see that in the presidential symposium. This is in the context of our mission to improve access to rare disease cell and gene therapy (CGT). This is the guiding principle of our strategic plan: we want to work for universal access to CGT. There are two orthogonal axes to this: I’m focusing on rare and ultra-rare diseases. ASGCT is going to continue to work in parallel on universal access in a more global context.
We have created a first-of-its-kind exchange for shelved CGTs. An increasing number of CGTs for rare and ultra-rare diseases are being discontinued or deprioritized after they reach the clinical stage—not because they lack clinical efficacy but because they lack market viability. We have partnered with Orphan Therapeutics Accelerator to create a new entity called CGTxchange. This collaborative venture is meeting the need of these promising clinical-stage CGTs that are not progressing. This entity will be an AI-enabled digital platform that will list the available clinical-stage CGT programs and generate AI-enhanced profiles, digest the data, score them for their level of advancement and the robustness of their responses, and essentially shorten the due diligence that investors normally have to do, enabling the connections to work faster.
I estimate there’s at least 50-100 of these programs. We had our own personal experience with Sio Gene Therapies [formerly Axovant] on both GM1 and GM2 gangliosidosis. This is part of a broader set of initiatives. Over the past few years, we created a taskforce in response to this increasing rate of discontinuation of these therapies. The two main outgrowths that the ASGCT board has endorsed are to create a consortium of CGT developers that might be able to offer non-profits less expensive manufacturing in a limited way but also work toward a drug master file sharing data for those who benefit from the less expensive vectors—in addition to the clearinghouse I just mentioned.
GEN: What else is new this year?
Flotte: A new thing for ASGCT is we’re having a patient advocate presenting. Terry Pirovolakis pioneered the CGT therapy for spastic paraplegia type 50 (SPG50) by developing his own company, Elpida Therapeutics, which has taken SPG50 to the clinic and now is doing that for other rare and ultra-rare diseases.
The second example is from Claire Booth, MBBS, PhD, (Great Ormond Street Children’s Hospital, London). Her team has received market authorization to be the
pseudo-commercial manufacturer of a fully licensed therapeutic for different forms of SCID.
Those are two direct examples of alternatives to get things to the clinic, other than getting a new commercial sponsor. [Hopefully] we can end up getting more of those picked up, whether through the CGTxchange or direct outreach. We’re also going to honor Timothy Yu, MD, PhD, with the Jerry Mendell Translational Research Award. He will be talking about the N=1 Collaborative with the parallel effort with oligonucleotide therapeutics. There is a purposeful theme to this meeting, aiming to make a big change in how things can get to the clinic and stay in the clinic.
GEN: Last year in New Orleans, the conference was dominated by the Baby KJ story. Will anything stand out in the same way this year?
Flotte: We are honoring the three primary authors of the Baby KJ story—Kiran Musunuru, MD, PhD, Rebecca Ahrens-Niklas, MD, PhD, and Fyodor Urnov, PhD.
I have also selected the work of Lindsey George, MD (Children’s Hospital of Philadelphia) as a presidential abstract. She is going to present the first case of an AAV-induced tumor—or at least an aggressive and autonomously growing malignancy…. This occurred in an MPS1 patient who received a high dose of AAV into the ventricles. It is not exactly a meningioma, but it’s arising from the neuroepithelial cells lining the ventricles. The tumor has AAV integrated with a strong promoter immediately upstream of a known oncogene. I put that into the presidential lecture, even though it’s not good news—but I’m not a [gene therapy] campaign manager here! I think this is a significant finding that we’ll have to pay attention to.
Lindsey is not saying that nobody should ever do this again. She’s going to point out aspects of this that were very manageable and how this patient overall has a dramatically better outcome than they would have without the therapy. In a way, [this is] somewhat like when those leukemia cases developed in Europe in the early SCID [gene therapy] trials. It is in a way parallel to that.
GEN: This will be your last conference as president of ASGCT!
Flotte: Yes, it ends on May 15th! We only get to be president for one year. I started the Rare Disease Task Force as vice president. This was my cause over the past three years [as an officer]. I’m very pleased we were able to stand this up.
We have an actual corporation, a joint venture, 50% owned by ASGCT. We set up this manufacturing consortium. Somewhat related, we set up our own charitable foundation, the ASGCT Foundation. We will have our first event—a gala at the conference. It will have a lot of time to grow. The foundation has just been incorporated as a subsidiary not-for-profit.
GEN: How do you view things at FDA currently?
Flotte: We will have a fireside chat with the new director of CBER, Katherine Szarama, PhD. We are very encouraged—she’s a very highly trained professional. We love that FDA is paying a lot of attention to rare diseases, but we need some scientific and evidence-based guidelines on how to do this consistently. We’re looking to someone who has regulatory experience.
GEN: What else has got you and your colleagues in the gene therapy space excited of late?
Flotte: I’m hoping we’re going to better understand high-dose AAV toxicity… I think what we’ve got is several different syndromes, but many of them may have a common link… We’ve been seeing with high-dose AAV a very broad distribution, but the doses are incredibly high and there have been deaths—the DMD patient deaths that occurred in the first two weeks are the best-known examples, but there have been other ones.
In my lab, we’re trying to figure out the primary pathogenesis. We have found a number of situations with unexpected vector expression in the endothelial cells and then seeing vascular leakage into some of these tissues causing tissue injury. So, in the post-mortem analysis we helped on, we saw high expression in the lungs and alveolar capillaries. They had diffuse leakage into the capillaries leading to a syndrome known as acute respiratory distress syndrome (ARDS). But in some of the others where they’re seeing some complement activation, we think that small vessel injury could be a convergent pathway. Now, where does this come into play in the broader sense?
One of the holy grails of recent AAV gene therapy is to design an AAV capsule that efficiently crosses the blood-brain barrier. Many diseases that are appropriate for AAV are diseases of the central nervous system (CNS). You can think of, for instance, the easiest cells to access in the CNS are the spinal motor neurons, hence the SMA1 treatment, Zolgensma. So, if you treat an SMA newborn, that is essentially solved or at least adequately solved. But in none of the diseases that affect the brain have we seen an IV gene therapy that is robustly efficacious—just giving an AAV at a high enough dose to get across the blood-brain barrier. Many different companies are trying to develop AAV capsids that will penetrate the blood-brain barrier, the first one that got to clinic was a vector designed by Capsida Biotherapeutics. But the first patient treated on the Capsida trial developed cerebral edema and died.
One of the important challenges for the field is to understand if we can separate a blood-brain barrier penetration from endothelial cell toxicity, because you could think perhaps a vector designed to get through the blood-brain barrier could cause injury as it crosses to the endothelial cells in the brain. I think there may be ways around this, but to me this is a central issue because the CNS is affected in so many single-gene disorders. The parents see a child who has a disability or degenerating, as in Tay-Sachs, and they want to be able to do an IV therapy. They don’t want to have to have a direct brain injection or some other invasive intervention. So that’s what I’m looking for at ASGCT 2026.
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