Radically different
Nature Neuroscience, Published online: 15 May 2026; doi:10.1038/s41593-026-02287-z
Pagani et al. used cross-species fMRI to reveal two autism subtypes, characterized by lower and higher brain connectivity and linked to synaptic and immune-related pathways, respectively.
In a discussion about the best fruits, my STAT colleague Alexa Lee and I agreed that peaches have been mid in recent years. Is this just a New York City problem? Please dial in with your fruit feelings.
You know what’s not mid? STAT’s excellent journalism on health and medicine. Subscribe here.
BOSTON — In a potentially significant advance for the genome editing field, researchers from the biotechnology company Caszyme and the Vilnius University Institute of Biotechnology in Lithuania have developed a potent and compact variant of Cas12l nuclease. Giedrius Gasiūnas, PhD, Caszyme co-founder and CEO, presented highlights of the research at ASGCT.
The work represents “a great example of the potential of continued mining for novel Cas effectors within the bacterial metagenomic diversity dark matter,” said Rodolphe Barrangou, PhD, Editor in Chief of The CRISPR Journal, which will shortly be publishing a paper on the Lithuanian team’s results.
“We need more diverse effectors to address the technical shortcomings of the CRISPR toolbox,” Barrangou continued. “This study is a great illustration of the potential of mining bacterial diversity.”
The Lithuanian team, including veteran gene editor Virginijus Siksnys, PhD—winner of the 2018 Kavli Prize with Jennifer Doudna, PhD, and Emmanuelle Charpentier, PhD, for CRISPR gene editing—used a hybrid approach to optimize Cas12l. By combining cryo-electron microscopy (cryo-EM) structure-guided design with artificial intelligence (AI) protein language models, the team was able to engineer a variant (Asp2Cas12l M82) that overcomes the known efficiency limitations of the Cas12l family.
Although Cas9 has widespread utility, including clinical applications, researchers have long considered its relatively large size and requirement for G-rich protospacer adjacent motifs (PAMs) problematic. The Cas12l family, discovered in the Armatimonadota bacterial phylum, offers a more compact size (867 amino acids) and recognition of a C-rich PAM site.
But wild-type Cas12l enzymes exhibit lower editing efficiencies and higher target-to-target variation compared to Cas9. According to Gasiūnas, the new M82 variant is “reliable, precise and adaptable,” and shows promise for a wide range of therapeutic applications.
“Through our continued work exploring novel Cas systems, Caszyme is focused on advancing technologies that move beyond promise into practical use.”
The engineering of the M82 variant proceeded in two steps. First, the Caszyme researchers solved the 3D structure of Asp2Cas12l complexed with an sgRNA and DNA to high resolution (2.51 Å). This revealed a unique “bracelet” architecture whereby the nuclease encircles the DNA target via interlocking helical bundles and a proline-rich string.
Next, the team introduced arginine substitutions at dozens of positions in the molecule to enhance electrostatic attraction to the negatively charged DNA backbone. This work included the production of an M67 variant, which provided a 7-fold improvement in indel editing over the wild-type nuclease.
To engineer further refinements, the Caszyme group turned to AI, specifically the ESM-2 protein large language model. This model predicted evolutionary hotspots considered likely to preserve or enhance function. Integrating these AI-derived substitutions—Q572R in the bridge helix and F607S in the RuvC domain—resulted in the final M82 Cas12l variant, illustrating the value of AI-supported engineering rather than deploying protein-directed evolution.
Gasiūnas presented data showing that M82 possesses good activity across recalcitrant gene targets, reducing the target-to-target variation that plagues many novel nucleases. In head-to-head comparisons in HEK293T cells, M82 demonstrated an average indel editing rate of 67.4%, nearly identical to that of Cas9 at overlapping target sites. This potency was consistently maintained across several delivery formats, including plasmid DNA, mRNA, and ribonucleoprotein complexes.
The Caszyme group also showed excellent M82 efficiency in homology-directed repair (HDR). In experiments targeting the AAVS1 locus, M82 facilitated a site-specific gene insertion frequency of 39%, outperforming Cas9 in the same context. Using single-stranded donor templates, HDR rates reached as high as 56%. Gasiūnas suggested that the staggered cut produced by Cas12l may inherently steer DNA repair toward precise correction rather than stochastic indels. With regard to safety, Caszyme found that M82 Cas12l maintained a high degree of on-target precision. Secondary editing signals were largely detected at or near the lower limits of assay sensitivity, suggesting a low risk of off-target cleavage.
The compact size of the M82 variant makes it an attractive candidate for adeno-associated virus-mediated delivery, which has strict limits on cargo size. “It is no secret that the CRISPR space has faced challenges and concerns in recent years,” Gasiūnas said. “However, we are confident in M82’s ability to create headroom for scientists to stand up and innovate within.”
Cas12l is not the only compact Cas nuclease gaining attention, of course. In a talk preceding Gasiūnas’ presentation, Zhaoshi Wu, PhD, co-founder and chief technology officer of Shanghai-based Castalysis Bioscience, presented an update on Cas12n, details of which were first published in Molecular Cell in 2023. The nuclease was touted as being the first independent CRISPR-Cas complete gene family uncovered by Chinese scientists within China’s territory.
Touted as a next-gen ultra-compact gene editing system, Cas12n (branded as alphaCas) consists of just 450 amino acids, and possesses structural similarity to TnpB. Cryo-EM structural analysis led the Chinese investigators to optimize the molecule for non-viral in vivo delivery. Preclinical experiments showed robust genome editing in a mouse model by targeting PCSK9 using lipid nanoparticle delivery, resulting in sharp drop in serum LDL levels.
Wu said his company is on target to begin its first clinical before the end of 2026. But he faced an uncomfortable moment during audience questions. Fyodor Urnov, PhD, challenged Wu’s claim that an inherent advantage of Cas12n was its safety profile compared to Cas9. Urnov pointed out that Intellia Therapeutics has two ongoing Phase III in vivo trials using CRISPR-Cas9 that show no immunogenicity concerns using LNP delivery.
Urnov later congratulated Wu on the rest of the company’s data and wished them success.
The post ASGCT 2026: AI-Optimized Cas12l Gene Editor Offers Compact Cas9 Alternative appeared first on GEN – Genetic Engineering and Biotechnology News.
The Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute launches its next two-year fellowship for professionals pursuing evidence-based approaches across diverse, underserved global communities
New York, NY—Applications are now open for the 2026 Communicator Fellowship at the Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute. The fellowship is designed to support a new generation of communicators working to shape child and adolescent mental health care in low- and middle-income countries, in addition to the SNF Global Center’s core country offices in Brazil, Greece, and South Africa. Up to three professionals working in public communications, including journalists, broadcasters, and podcasters, will be selected for the two-year program.
The Communicator Fellowship is part of the SNF Global Center’s broader mission to reduce gaps in data and care, catalyze system-level advancements, and transform child and adolescent mental health care by turning evidence into action, scaling culturally appropriate solutions, and building a global network of experts so young people everywhere can access support when they need it.
The application deadline is June 15, 2026. Fellows will be selected and announced by early August 2026. In addition to financial support of up to $100,000 USD, fellows will receive training, mentorship, and networking opportunities.
At a time when one in five young people are experiencing mental health or learning challenges, with most cases beginning by age 14, effective and accurate communication is urgently needed.
At the Child Mind Institute, we believe that translating research into accessible knowledge that empowers young people, families, and communities is integral to advancing mental health care. The Communicator Fellowship builds on this commitment by supporting professionals who can bring evidence-based mental health information to the public in clear, engaging, and culturally relevant ways.
Vinicius Gaby Vieira Rego, MD, of Brazil, a current Communicator Fellow with the support of the Institute of Psychiatry at the University of São Paulo, exemplifies this mission. Working with youth, Dr. Rego is co-creating a multi-platform literacy hub designed to combat harmful misinformation by empowering Brazil’s young leaders.
“I am deeply grateful for the opportunity to join the SNF Global Center’s network of fellows to support adolescent mental health in Brazil through communication,” said Dr. Rego. “This fellowship will enable a multi-channel communication project aimed at strengthening mental health literacy and peer-support capacity — with young people and for young people — across the country.”
As a fellow, Dr. Rego’s work directly addresses complex mental health challenges faced by young people in Brazil, while contributing to broader global efforts to improve communication about mental health care.
“In the current digital environment, where adolescents are exposed to a high volume of mental health content, the need for evidence-based information that resonates with young people has never been greater,” said Guilherme Polanczyk, MD, PhD, associate professor of Child and Adolescent Psychiatry at the University of São Paulo. “We are proud to endorse a project committed to supporting how young people and their communities understand and reflect on their mental health.”
Other current fellows are leading high-impact projects dispelling misinformation, reducing stigma, and increasing youth engagement — all while bringing critical attention to links among mental health, climate change, and human rights. Through partnerships, these efforts are transforming the future of youth mental health across the globe.
“Vinicius’s project is ambitious, and with the support of the Institute of Psychiatry at the University of São Paulo, we know it will provide young people in Brazil with much-needed resources to support their mental health,” said Peter Raucci, Director of Global Fellowship Strategy of the SNF Global Center at the Child Mind Institute. “What we’re seeing through the Communicator Fellowship is how quickly ideas can move from concept to culturally relevant, real-world impact.”
Application deadline: June 15, 2026
Fellows announced: August 2026
About the SNF Global Center at the Child Mind Institute
The Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute brings together the Child Mind Institute’s expertise as a leading independent nonprofit in children’s mental health and the Stavros Niarchos Foundation’s deep commitment to supporting collaborative projects to improve access to quality health care worldwide. The center is building partnerships to drive advances in under-researched areas of children and adolescents’ mental health, and expand access to culturally appropriate training, resources, and treatment in low- and middle-income countries. This work is conducted by the Child Mind Institute with support from SNF through its Global Health Initiative (GHI).
About the Child Mind Institute
The Child Mind Institute is dedicated to transforming the lives of children and families struggling with mental health and learning disorders by giving them the help they need. We’ve become the leading independent nonprofit in children’s mental health by providing gold-standard, evidence-based care, delivering educational resources to millions of families each year, training educators in underserved communities, and developing tomorrow’s breakthrough treatments.
The post Applications Open for the SNF Global Center Communicator Fellowship appeared first on Child Mind Institute.
BOSTON — A team at Children’s Hospital of Philadelphia (CHOP) led by Rebecca Ahrens-Niklas, MD, PhD, and Lindsey George, MD, has described a case of a brain tumor linked to a rare integration of adeno-associated virus (AAV).
George presented the work at the American Society of Gene and Cell Therapy (ASGCT) conference in a plenary talk selected as the “presidential abstract” by ASGCT president, Terry Flotte, MD. The study, “Neuroepithelial tumor with AAV integration after intracisternal magna vector delivery,” was published in the New England Journal of Medicine.
Over the past 25 years, some 6,000 patients have been treated with some form of AAV gene therapy. In all that time, George said, there have been no established long-term safety concerns, although genome integration events have been reported in mouse and dog studies. But the case documented by George and colleagues at CHOP suggests that the gene therapy field may need to pay more attention to this potential occurrence.
The story began with a 5-year-old boy with an inherited lysosomal disorder, severe MPS1 deficiency (Hurler subtype). The patient received enzyme replacement therapy at six weeks of age, followed by a cord blood stem cell transplant at age four months.
Investigators chose to perform gene therapy when the patient was 13 months old to deliver the iduronidase (IDUA) gene. The vector chosen was an AAV9 serotype, using a cytomegalovirus enhancer and a chicken beta-actin promoter driving the gene. The virus was administered into the boy’s cisterna magna in the base of the skull.
When the boy was five years old, a routine neurological scan revealed a large intraventricular mass that had not been observed two years earlier. Analysis of the tumor revealed it was a PLAG1-driven neuroepithelial tumor—indeed, PLAG1 expression was almost 300 times higher than in other central nervous system tumors studied at CHOP. (PLAG1 is usually only expressed during embryogenesis.)
Surgery to remove the tumor was successful. Eight months after surgery, there are no signs of tumor growth. The boy is also showing advanced neurocognitive function.
George described RNA sequencing of the tumor, which revealed the fusion of a fragment of the AAV9 vector cassette to exon 5 of the PLAG1 gene on chromosome 8. The resulting transcript is predicted to encode a PLAG1 derivative containing five zinc-finger DNA-binding domains and a C-terminal transcriptional activation domain, which was previously reported to function as a transcriptional activator.
Curiously, the chimeric junction also included a segment of human chromosome 10, which George suspects originated during the vector manufacturing process. The integration event was present in about 40% of the total reads, suggesting integration into one of the two PLAG1 alleles.
George concluded her talk by noting that while the clinical outcome in this patient is so far encouraging, this is evidence that AAV integration can be associated with oncogenesis. The study underscores the need to monitor the most heavily transduced tissues after AAV gene therapy.
While the gene therapy community should be cautious in extrapolating this single case report across all AAV gene therapy programs, George said the study supports the use of the lowest feasible vector dose as well as tissue-specific promoters.
George noted that detection of the integrated AAV vector DNA was challenging, in part because of rearrangements of vector DNA. The use of several complementary techniques—long-read DNA sequencing, targeted PCR amplification, and RNA sequencing—was required to confirm the integration.
George and coworkers closed their paper, noting that, “Our findings support the hypothesis that rare AAV integration can contribute to human oncogenesis, which emphasizes the need to optimize gene delivery methods and monitor transduced tissues after treatment.”
The post ASGCT 2026: Rare Instance of AAV Integration into Human Genome Linked to Brain Tumor appeared first on GEN – Genetic Engineering and Biotechnology News.
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.
China’s short drama industry is fueled by bite-sized, melodramatic, and smutty shows built for smartphone scrolling. Now, many are being made entirely with AI: no actors, camera operators, cinematographers, or CGI specialists required.
An average of 470 AI-generated short dramas were released every day in January. Production timelines have shrunk from months to weeks, while costs have dropped by up to 90%. Storytelling is also increasingly driven by performance data.
The format is rapidly expanding overseas while reshaping the work of writers and production crews. Read the full story on AI’s dramatic impact on China’s short drama industry.
—Caiwei Chen
The World Health Organization’s latest global statistics report reads less like a progress update than a warning sign. Progress on some of the world’s biggest health threats is stalling, and in some cases reversing altogether.
There were 1.3 million new HIV cases in 2024, malaria is resurging, vaccination rates are slipping in the Americas, and 42.8 million children are suffering from severe malnutrition. The world is now far off track from meeting many of the UN’s major health goals by 2030.
Here’s what the numbers reveal about the state of global health.
—Jessica Hamzelou
This story is from The Checkup, our weekly newsletter giving you the inside track on all things biotech. Sign up to receive it in your inbox every Thursday.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 As their trial goes to the jury, Musk and Altman face lying accusations
Lawyers hammered the rivals’ credibility in their closing arguments. (WSJ $)
+ Musk was accused of “selective amnesia.” (Reuters $)
+ The pair are in court over OpenAI’s future. (MIT Technology Review)
+ And their trial has made everyone look bad. (Wired $)
2 AI data centers are straining America’s power grid
Nevada is redirecting electricity from Lake Tahoe to AI. (Ars Technica)
+ Utah is getting a giant data center despite water shortage fears. (Guardian)
+ No one wants a data center in their backyard. (MIT Technology Review)
3 OpenAI is mulling legal action against Apple over its ChatGPT integration
It hasn’t got the expected benefits from its deal with Apple. (Bloomberg $)
+ OpenAI is frustrated by the promotion of the ChatGPT integration. (NYT $)
4 Anthropic has agreed terms for a $30 billion funding deal
At a $900 billion valuation, which leapfrogs OpenAI’s. (The Information $)
+ Dragoneer, Greenoaks, Sequoia, and Altimeter are leading the round. (FT $)
6 Washington and Beijing will hold formal talks on AI safety
They’ll discuss guardrails on AI. (CNBC)
+ And a protocol to stop nonstate actors getting powerful models. (NYT $)
5 Alphabet and Amazon are using “unprecedented” borrowing to fund AI
They’re tapping the foreign debt market at new levels. (FT $)
+ People can’t agree on what the AI bubble is. (MIT Technology Review)
7 Big Tech has turned to Sesame Street to deflect scrutiny of screen use
Sparking accusations of encouraging children’s tech dependence. (Reuters $)
8 Anthropic’s feud with the White House threatens other businesses
Figma and Tenable say it will harm their ability to sell software. (Bloomberg $)
9 Autonomous agents staged a digital crime spree during a safety test
The “AI Bonnie and Clyde” then deleted themselves. (Guardian)
10 A poop app analysis app offered to sell photos of users’ stools
The images were used for AI training. (404 Media)
Quote of the day
—Danielle Hughes, North Lake Tahoe resident and CEO of Tahoe Spark, tells Fortune that residents are being sidelined as their energy supplier prioritizes data centers.
One More Thing
Just before Christmas, a pastor preached a gospel of morals over money to several hundred members of his flock. But the preacher wasn’t religious, and his congregation wasn’t a church. It was All Tech Is Human, a nonprofit devoted to ethics and responsibility in tech.
Founded in 2018, the organization has built a fast-expanding community for people who believe technology should focus less on profits and more on the public interest. It’s also drawing people searching for meaning and connection in a digital world.
Find out why thousands of people are turning to tech ethics communities for guidance and connection.
—Greg M. Epstein
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.)
+ Go behind the scenes of the new Lucas Museum of Narrative Art.
+ Marvel at this robot folding and launching paper planes as quickly as possible.
+ Watch the moving moments rescued animals reunite with the humans who saved them.
+ Peer into the heart of a barred spiral galaxy in this stunning new capture from the James Webb Space Telescope.
Ovarian cancer remains one of the deadliest gynaecological malignancies, with high-grade serous ovarian cancer (HGSOC) accounting for the majority of deaths.1,2 Despite advances in surgery and chemotherapy, most patients are diagnosed at an advanced stage, and the 5-year survival rate has stubbornly remained below 50% for decades.3 A major obstacle is that the traditional FIGO staging system, while useful for prognosis, does not explain why patients within the same stage often follow dramatically different clinical trajectories.
The conversation about social media and mental health keeps circling back to the same question: Should we ban children from these platforms? It is an important question. But it is not the only one, and it shouldn’t be.
The post Built to Hook: Holding Platforms Accountable for Mental Wellbeing | Lunch & Learn appeared first on Mental Health Europe.
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.