Atlases have long guided us through uncharted territory. Now, an AI-generated atlas by Google DeepMind seeks to do the same for the vast landscape of our DNA.

Ever since the Human Genome Project, scientists have painstakingly traced the myriad DNA mutations that contribute to health and disease. But that quest has largely been stymied by the genome’s vast scale. Only two percent encodes the proteins that make our bodies work; the rest may control how genes are turned on or off or be junk left over from evolution.

With roughly nine billion possible DNA letter swaps, testing each one in the lab is impossible. Making sense of their interactions is an even tougher challenge. Yet these changes often contribute to differences in risk for cancer, dementia, and other medical scourges.

DeepMind’s new atlas could lend researchers a hand. Generated from the company’s AlphaGenome AI released last year, the searchable database predicts the effects of every possible DNA letter swap. Thousands of researchers have already experimented with AlphaGenome, but those studies required some coding prowess, raising the barrier to entry.

AlphaGenome Atlas may make the AI more accessible. Analysis of individual DNA changes, down to the level of specific tissues, is readily available through a web portal for non-commercial use. As the most comprehensive catalog of how genetic mutations might affect molecules in the body, it could help uncover the mutations underlying traits and illnesses. By charting the genome’s “dark matter”—regions that don’t encode proteins— it might also reveal hidden rules that direct gene activity. The details are described in a paper.

“This represents the first time that any researcher in the world can access a comprehensive map of the human genome and its variations by simply opening a browser,” said Pushmeet Kohli, DeepMind’s vice president of science, in a press briefing.

The Language of Life

With just four DNA letters—A, T, C, and G—our genomic instructions seem simple. But the actual genetic playbook is far more complex. After piecing together the first draft of the human genome at the turn of the century, scientists were surprised by how little of it guided protein manufacturing. A staggering 98 percent didn’t seem to do much, earning the nickname junk DNA.

Long overlooked, these non-coding sections have increasingly captured attention for their role in regulating gene expression. Some DNA snippets can even operate thousands of letters away from the genes they control, making their involvement tough to decipher.

Non-coding DNA is also highly dynamic. Some genetic chunks can be duplicated or cut out as cells divide. Others jump to distant locations, reverse their sequences, or elbow their way into protein-coding genes.

Single-letter swaps are among the most prevalent DNA mutation. These can be relatively harmless. But they also can lead to diseases such as sickle cell anemia or raise a person’s “bad cholesterol” levels, increasing the risk of heart attacks. Gene-editing clinical trials are already underway to tackle these problems. But engineering a safe and effective treatment requires knowing which DNA swaps to make, and that’s been a roadblock.

Here’s where AlphaGenome comes in. Formally released early this year, the AI works in three steps. First, it spots short patterns in DNA sequence. Then it shares that information across a larger region of the DNA strand, letting it connect local patterns to distant letters. Finally, AlphaGenome translates those patterns into predictions of downstream biological effects.

The AI is customizable for different projects, allowing researchers to home in on DNA changes related to their specific questions. But it can only be accessed through an automated programing interface (API) which requires writing code and makes the data harder to access.

“AlphaGenome is helpful for analyzing specific variants and has found widespread use in research, but we wanted to show researchers a big-picture view of variants across the entire genome,” wrote the DeepMind team in a blog post.

Genome Cartographer

The new atlas does away with much of the coding and analysis, allowing researchers to search for DNA variants across the genome to see their potential effects.

To build the database, the team computed predictions for all three possible swaps at every DNA letter—for example, changing A to T, C, or G—resulting in a whopping petabyte of data.

As with AlphaGenome itself, the atlas generates thousands of predictions about how DNA changes affect molecular processes in different tissues. These include what happens when a nearby gene is switched on or how changes in the shape of chromatin, the tightly folded form of DNA, alter its biological activity.

“Just as an atlas is a collection of maps, linking together features of the land like altitude and location, AlphaGenome Atlas charts the molecular effects of DNA variants across the genome,” wrote the team.

But interpreting the atlas takes more work. With billions of potential changes, which ones should researchers prioritize?

To help them navigate the most promising variants, the team also developed a single metric to measure their predicted effects. Called the AlphaGenome Variant Impact (AVI) score, it combines AlphaGenome with AlphaMissense, a model that predicts the effects of mutations in protein-coding regions. Together, these two tools help distinguish harmless mutations from those more likely to play a role in disease.

In collaboration with the Broad Institute, the score has already helped researchers find and prioritize a non-coding DNA variant that may contribute to severe epilepsy. Rare disease researchers, who often lack the funding and computing resources needed to run genomic AI models directly, could particularly benefit from the atlas.

“If somebody is studying a disease, and they don’t have any idea about what cell types to look for or what molecular processes are impacted, then starting with an AVI score…is a great starting point to help you prioritize variants and try to find that needle in the haystack,” said genomic lead and study author Žiga Avsec in a press conference.

Beyond tackling genetic diseases, the atlas could also help decode mysterious non-coding motifs, or snippets of DNA scattered across the genome. Some motifs control the production of messenger RNA, which carries genetic instructions to the cell’s protein-making factories. Others alter the activity of individual genes. But most remain poorly understood, if they have a function at all.

Linking these motifs to large health databases, such as the UK Biobank, could map the gene interactions and resulting proteins underlying height and other complex traits. The atlas could also help AI agents rapidly generate hypotheses for human collaborators to explore in the lab.

AlphaGenome Atlas isn’t meant to replace real-world experiments. And unlike AlphaFold, DeepMind’s protein structure-predicting AI that garnered a Nobel Prize, DeepMind needs to further boost its accuracy. But the atlas is shaping up to be a valuable guide for genomic explorers navigating the vast DNA landscape that makes us human.

The post Google’s Genome Atlas Predicts the Effect of Every Possible DNA Mutation appeared first on SingularityHub.

It’s a hot GLP-1 drug summer. Semaglutide—better known as Ozempic and Wegovy—seems to be everywhere. The blockbuster weight loss aid mimics a natural hormone that tells the brain “you’re full,” making it easier to shed pounds without the constant hunger and cravings that make traditional dieting miserable.

The drug may also have longer effects. A new study in mice suggests that starting semaglutide in old age extends lifespan roughly 12 percent. The mice regained their curiosity and memory and improved on myriad age-related hallmarks. Chronic inflammation cooled. Senescent “zombie cells” dwindled. Their genomes and proteins became more stable, and the hippocampus—a brain region crucial for learning and memory—sprouted new neurons.

The findings are reminiscent of calorie restriction, a way to boost longevity and stave off age-related health problems, at least in lab animals. But sticking to a diet for years, let alone decades, is tough. Scientists have long searched for a drug that could deliver some of the benefits without hunger pangs. Semaglutide seems to fit the bill, with surprising perks beyond dieting.

“If these results from mice hold true in people, this is a promising hint that people taking GLP-1R agonists [GLP-1 drugs] may have an age-slowing benefit as well as benefits to reducing diabetes and obesity,” said Tara Spires-Jones at the University of Edinburgh, who was not involved in the study.

But don’t go ordering GLP-1 drugs online just yet. The study used inbred female mice, whose physiology differs from that of women aging through or beyond menopause. Rapid weight loss in people taking these drugs can also reduce lean muscle, potentially increasing fragility in older people. And while GLP-1 drugs are already being tested in the battle against neurodegenerative disorders, whether they sharpen the aging brain remains an open question.

Still, longevity researchers are cautiously optimistic.

“The findings reframe a key question that has often been asked back to front,” wrote Maria Fernandez and Rafael de Cabo at the National Institute of Aging, who were not involved in the study. “Rather than considering the broad health benefits of GLP-1 drugs as something to be explained one disease at a time, these results suggest that the positive effects have a common cause: slowed aging.”

Fountain of Youth

One way to live healthier and longer is seemingly mundane: adopt a healthy lifestyle.

Diet and exercise have repeatedly been linked to better health in our twilight years. As we age, our bodies slowly break down. Damage and mutations accumulate in DNA. Telomeres, the protective caps at the ends of chromosomes, grow shorter, contributing to genomic instability. The molecular switches that turn genes on or off go haywire, and our cells become less able to make working proteins and clean up damaged ones.

There’s more. Mitochondria, the cell’s power plants, struggle to produce energy and leak toxic molecules. Damaged cells stop dividing, lose their function, but stubbornly refuse to die. Instead, they leak a toxic chemical soup that damages tissues. Chronic inflammation flares, and stem cells run out of steam, making it harder for the body to regenerate or repair itself.

Together called the hallmarks of aging, this laundry list has long challenged scientists looking for a silver bullet against the march of time. They have discovered some exotic options. Transferring components of young mice’s blood to older recipients has rejuvenated faltering hearts, kidneys, and brains. And clearing senescent “zombie” cells with drug cocktails or genetic engineering has attracted billions of dollars in investment.

But perhaps the most studied, and most robust, intervention is caloric restriction. In flies, rodents, and other lab animals, slashing energy intake without causing malnutrition has repeatedly extended lifespan and delayed multiple age-related diseases. Restriction triggers broad changes, including improved metabolism and insulin sensitivity. It also helps prevent damage to cells. In humans, moderately reducing calories seems to improve heart health and slow the speed of biological aging.

Sticking to a diet for years on end, however, is hardly sustainable.

Cheat Code

GLP-1 drugs may make it easier.

Originally designed to control blood sugar and appetite, the drugs have also shown promise for reducing rates of cardiovascular, kidney, liver, and neurodegenerative diseases, at least in people with obesity or Type 2 diabetes. Clinical trials are now exploring their effects in people with metabolic liver disease, which becomes more common and consequential with age.

Not all these effects can be explained solely by weight loss, raising a bigger question: How can a single class of drugs influence so many seemingly unrelated conditions that often crop up with age?

“If GLP-1 medications slow down the aging process itself, a wide range of clinical benefits is

exactly what would be expected, because aging is the root of most chronic diseases,” wrote Fernandez and de Cabo.

To test that theory, the team gave daily semaglutide injections to 20-month-old female mice—roughly comparable to women in their early-to-mid 60s—for as long as they lived.

Compared to a group of mice given saline, the treated mice lived an average of 834 days, versus 724 days for a control group. Both groups could feast on standard chow to their hearts’ content. After just three months of treatment, the mice taking semaglutide were more lively and curious than their peers. They readily explored new environments, balanced better on a skinny rotating rod, ran faster on a tiny treadmill, and solved mazes more quickly.

Under the hood, semaglutide blunted the hallmarks of aging across the board. Stem cells in the bone marrow and hippocampus sprouted, suggesting renewed regenerative capability. DNA damage and protein and energy dysfunction declined. Zombie cells partially disappeared.

The results weren’t simply a consequence of eating less. In another three-month experiment, the team compared the drug with a calorie-restricted diet that cut energy intake by 24 percent—the same reduction seen in the semaglutide-treated mice.

The drug seemed to have a leg up. Compared with caloric restriction, it produced more improvement in cognition and blood sugar control, without the metabolic adaptations normally driven by hunger, such as lowered energy expenditure. The mice also showed fewer signs of hunger. They ate on a normal schedule rather than prowling for food before feeding time and gobbling rations once available.

Genetic sequencing of the liver found semaglutide triggered similar molecular signaling pathways as caloric restriction, like for example, those that sense nutrient availability, cell stress, and proteins involved in longevity. Both interventions tamped down inflammation and boosted genes involved in handling fats, but they didn’t follow the exact same biological playbook.

The findings raise the “intriguing question of whether GLP-1 drugs target an alternative biological route into aging that has its own side effects and therapeutic ceiling,” wrote Fernandez and de Cabo. Exactly how that route works remains unclear, but the team is eager to find out.

The findings are promising, but the study also has major limitations. It didn’t directly compare dieting and semaglutide for lifespan extension. And because gender affects the aging process, the team will need to see if the results hold in males. Then there’s the potential loss of lean muscle, a serious concern for people who are already frail or saddled with age-related health conditions.

Even so, “semaglutide is probably the best caloric-restriction mimetic I have seen,” Tim Rhoads at the University of Wisconsin–Madison , who was not involved in the study, told Chemical and Engineering News.

Untangling semaglutide’s bonus effects could ultimately reveal new ways to slow—or even rewind—aging’s ticking clock.

The post Could GLP-1 Drugs Help You Live a Longer, Healthier Life? appeared first on SingularityHub.

The Alzheimer’s brain faces a double whammy. Toxic protein clumps build up inside and outside neurons to torpedo normal function and destroy delicate structures. Eventually, the cells die. The adult brain has an extremely limited ability to grow new neurons. Once gone, they’re rarely replaced. Over time, the brain withers, taking learning, memory, and cognition with it.

But there might be a sneaky workaround. The brain is packed with star-shaped cells called astrocytes that keep neurons healthy. They’re also shape-shifters. Under certain conditions, astrocytes can shed their identity and transform directly into mature neurons. In other words, they could be an abundant, untapped source of replacement neurons.

A team at the University of South Carolina has now taken advantage of this quirk. They engineered a tiny molecular cage and filled it with antibodies. Once inside astrocytes, the antibodies released a protein “brake” that normally keeps the cells’ identity stable. Free from this constraint, astrocytes in lab dishes and human brain organoids adopted the molecular signatures of neurons and eventually sparked with electrical activity.

In mice modeling Alzheimer’s disease, the treatment increased the number of neurons in the hippocampus, a brain region crucial for learning and memory and one of the first to falter in the disease. Treated mice resumed normal behavior and performed similarly to healthy mice on tests of learning and memory in a maze.

The approach fundamentally differs from existing methods and could “unlock previously inaccessible regenerative mechanisms,” wrote the team. If it proves safe and effective in clinical trials—and that’s a big if—the approach could one day tackle diseases beyond Alzheimer’s, such as Parkinson’s or amyotrophic lateral sclerosis (ALS).

Born Identity

The quest to treat Alzheimer’s has often been called the “graveyard of dreams.” The most common form of dementia, the disease affects roughly 24 million people worldwide and slowly eats away at thinking, memory, learning, and emotional regulation. Experts still debate Alzheimer’s root cause, but they largely agree that clumps of misshapen proteins called amyloid beta and tau exacerbate the disease.

Current FDA-approved treatments have had limited success. Antibodies that clear clumps offer only modest benefits to cognition and carry the risk of serious side effects. Other drugs, such as memantine, alter brain chemicals to protect damaged cells, rev up faltering brain circuits, and ease symptoms. But they don’t halt degeneration. As the disease progresses, benefits fade.

The central problem is frustratingly clear. Neurons die faster in Alzheimer’s than the brain can replace them. That’s why a landmark study nearly two decades ago made waves. Scientists once thought mature astrocytes were set in their fate. But the study showed the cells could be reprogrammed into neurons that generated electrical activity and formed connections with neighboring neurons in lab dishes to form working circuits.

Scientists later found a protein called PTBP1 that prevented this conversion. In 2020, a team injected an RNA-targeting form of CRISPR into the brains of mice modeling Parkinson’s disease. This reduced PTBP1 levels, which in turn, triggered the production of new neurons. The treatment restored the mice’s balance and motor skills, although some experts were skeptical.

While promising, CRISPR-based approaches can have unintended effects, and brain surgery is a tall order for any treatment. So, the team developed another way to release the PTBP1 brake.

Erase, Rewind

They turned to a duo of technologies that transport antibodies inside nanoparticle cages to degrade specific proteins inside cells. In this case, they used antibodies targeting PTBP1 and packaged the concoction in a biocompatible gel injected into the bloodstream.

Because of their large size, antibodies can’t usually cross the blood-brain barrier, a tightly sealed wall that keeps many molecules out of the brain. But the nanoparticle system helped ferry the antibodies across the blockade, nixing the need for brain surgery.

The team first tested the drug, called TN-PTBP1, on astrocytes grown in lab dishes. Within days, the cells lost their star shapes and began growing long, willowy branches characteristic of neurons. Their molecular profile also shifted, and the cells eventually burst with electrical signals.

The team recorded similar results in brain organoids, or “mini brains,” grown from human stem cells. Given a small electrical zap, the converted neurons responded in synchrony with neighboring neurons, suggesting they had integrated into existing neural circuits.

“The new neurons can become mature and survive,” said study author Peisheng Xu in a press release.

Next, they tested the drug in a mouse model of Alzheimer’s disease. By eight months, the mice showed clear signs of the disease. Their brains were highly inflamed and littered with toxic protein clumps. Neurons in the hippocampus had also substantially died off, similar to the loss seen in moderate to severe Alzheimer’s in humans.

The mice struggled with everyday behaviors, such as foraging for material to build nests. And they consistently performed poorly on a classic memory test where they had to find a location using visual cues (a bit like remembering where you parked your car).

Half the mice received TN-PTBP1 for two weeks; the others received saline. As expected, the drug reliably slashed PTBP1 levels in the brain. Over the course of the trial, treated mice increasingly improved on tests of cognition and memory, eventually performing at levels similar to healthy peers. Mice treated with saline showed no improvement.

“After just two injections, these mice became smarter,” said Xu. “Even after one injection, we already saw these mice’s behavior differ from that of the nontreated ones.”

The team found broader benefits too. The drug reduced inflammation and, surprisingly, the number of toxic protein clumps, suggesting it may have helped restore some of the brain’s ability to rid itself of waste. Neuron density also increased throughout the brain, and the treatment boosted production of proteins involved in maintaining the blood-brain barrier, which is often damaged in Alzheimer’s.

One unexpected, and welcome, effect was neurogenesis, the birth of new neurons in the hippocampus and another brain region. Neurogenesis declines with age, and whether it exists at all in adult humans is hotly debated. How TN-PTBP1 triggered it in mice remains a mystery. It’s also unknown how much the new neurons contributed to the animals’ recovery versus the direct conversion of astrocytes into neurons.

Still, it’s clear the drug boosted neuron numbers and “successfully reversed Alzheimer’s disease progression” in the mice, wrote the team.

The approach has a long road ahead. Many promising treatments in mice have failed in clinical trials. In the next few years, the team hopes to test the approach in monkeys, dial in the dose, and assess long-term safety. Astrocytes perform many tasks that keep the brain humming, and forcing them to abandon their identity could have unexpected consequences. There’s also the possibility newly converted neurons could scramble existing brain circuits rather than integrating safely, causing more harm than good.

But with rigorous testing, the drug could offer new hope.

The post This Drug Makes New Neurons in the Brain. Scientists Say It Reversed Alzheimer’s Symptoms in Mice. appeared first on SingularityHub.

The global nanorobotics market is forecast to reach $31.44 billion by 2034, driven by growing applications in targeted drug delivery, precision medicine and regenerative medicine, according to new research from Polaris Market Research. The research firm estimates the market at approximately $9 billion in 2025 and expects it to expand at a compound annual growth […]

This article was originally published on Undark. Read the original article.

In June, a community of mostly mathematicians released the Leiden Declaration on Artificial Intelligence and Mathematics, an articulation of the values they hope to preserve as automated systems are integrated into the practice of developing mathematical proofs. This is necessary because some frontier AI systems have shown striking capabilities for solving certain advanced mathematics problems, though independent tests show that AI still has important limits.

Although I’m not a member of the pure mathematics community in any strict sense, much of the declaration’s message resonated with me and was relevant to my own research interests as a computational biologist.

I’m encouraged that the mathematics community decided to take a stand on the issue and that it has been successful in organizing a large number of eminent mathematicians to sign the document. The Leiden Declaration, which originated at a conference held at Leiden University in the Netherlands, should spawn proper copycats, because what is true for mathematics is true for virtually every field that calls itself as a science. The inventions of mathematics percolate into the algorithms and statistical methods that help scientists design experiments, build simulations, and analyze data, from sociology to statistical physics and beyond.

I argue that biological fields should consider something of the sort, because the kinds of knowledge that biology generates and predicts are uniquely vulnerable to subversion and mischaracterization by artificial intelligence.

The conversation in the mathematics community has been illuminating, in that the declaration is a coordinated response to the powers and risks of AI, whose acceleration has felt like a Thanos snap, changing the universe in an instant. And part of the reason that mathematicians felt the effects so immediately is tied to the manner in which their research is conducted: A mathematical proof, in principle, is transparent and independently verifiable, and no proprietary equipment is (generally) required to check it.

The Leiden Declaration should spawn proper copycats, because what is true for mathematics is true for virtually every field that calls itself as a science.

As the Leiden Declaration notes, automated techniques now present mathematics with a new forgery problem: Because mathematical truths are fixed and verifiable, one can identify a counterfeit formalism by comparing it to the genuine proof. Biology, however, offers no such guarantee; our so-called “truths” are often noisy and context-dependent, making it nearly impossible to define what an authentic version should even look like. Some of the most widely appreciated biological principles (such as Mendel’s laws of genetic inheritance) are better described as powerful but limited in scope, and with well-characterized exceptions that don’t undermine the laws but refine their application. This is true for many biological theories. Boundary conditions, edge cases, and noise are not bugs but features of how the natural world works.

For example, a mutation that confers drug resistance to a virus with one genetic background may have a much weaker, neutral, or even harmful effect in another, because its impact depends strongly on the surrounding genetic context. This phenomenon, which biologists call epistasis, is not an exotic edge case but a powerful force across the biosphere in shaping the relationship between an organism’s genes and its expressed characteristics. And epistasis is just one of many examples of context dependence in biological systems, in which a finding that holds true in a dish falls apart in a body or has an effect in a mouse model but not in a primate.

When it comes to AI, the mathematician fears producing a counterfeit solution. But the biologist often cannot say, even acting in the fullest good faith, what the authentic version is supposed to look like.

Despite the differences between mathematics and biology, the life sciences should consider embarking on an exercise that is at least analogous to the Leiden Declaration. If nothing else, a biology version could borrow its structure and ambition. We should insist that researchers disclose their use of automated tools, that they are responsible for the veracity of their findings, that credit and accountability belong to people rather than to systems, and that early-career scientists be protected from incentives that prioritize high-volume output over genuine scientific insight.

A biology declaration should adopt these ideas and others, and emphasize additional provisions that are important to the field: the validation of AI-generated hypotheses against results from the wet lab, the management of training data drawn from the biological commons, and the heightened scrutiny owed to any model whose outputs will eventually touch a patient or an ecosystem. The last point is crucial: In the biomedical realm, AI’s missteps and triumphs will manifest in living bodies, with all of the associated corporeal, emotional, ethical, and legal consequences.

We should insist that researchers disclose their use of automated tools, that they are responsible for the veracity of their findings, that credit and accountability belong to people rather than to systems.

A biological Leiden Declaration must appreciate the nature of the data and observation in biology, and other particulars of the field. But the most important feature for responsibly managing the relationship between AI and living systems involves the durability of what is produced.

A mathematical declaration can aspire for permanence because verified proofs can remain valid across centuries. Biological understandings, on the other hand, tend to shift over time, sometimes rapidly. A policy hastily calibrated to the models of this summer might already be miscalibrated by winter. A declaration written in the hope of lasting a decade could risk spending much of that decade catching up.

If we are to orchestrate a responsible treatise for artificial intelligence in the life sciences, it should be adaptive: versioned, dated, revisited on a published schedule, and amended in the open by the very community it claims to represent. And because different subfields of biology have unique challenges—cardiology versus forest ecology, for instance—perhaps we need multiple declarations (but not too many).

The Leiden Declaration incorporates some of these elements, clarifying that its content reflects AI technologies and mathematical practice as of May 2026 and that updates on the document will be shared. Biology should make that feature part of the central architecture, wiring the process of revision into the document, so that updating it becomes a positive action rather than a confession of failure.

Fortunately, life scientists are well equipped for this task. We have long understood that structures unable to change with their environments rarely endure. It would therefore be a strange betrayal of our discipline to write a declaration that forgets this basic principle. Our policies for technological change must keep the dynamism of living systems at the center of how we imagine the future of biology.

The post Biology Needs an AI Declaration appeared first on SingularityHub.

The scent of fresh bread straight from the oven is intoxicating. As sugars and proteins react under heat, they create compounds that give golden-brown crusts their rich aroma. Called advanced glycation end products (AGEs), these molecules also form inside us. Our bodies are essentially ovens running at around 98 degrees Fahrenheit, and AGEs slowly build up over decades. They stiffen bouncy, elastic tissues and trigger lasting inflammation.

One of the hallmarks of aging, AGEs drive a range of age-related problems, increasing the risk of heart disease, diabetes, and eye and kidney troubles. In theory, clearing them out could turn back the clock. But previous attempts have failed, leading some scientists to suspect that the damage is irreversible. Once AGEs form, they stay.

Or maybe not.

A team at Revel Pharmaceuticals in San Francisco and colleagues took a new approach: They designed a synthetic version of an enzyme found inside microbes that targeted the most abundant type of AGE in several human tissues. In tissue from a 75-year-old donor, the enzyme reduced AGE levels to those seen in a 30-year-old, potentially giving the cells and their surrounding scaffold a chance to repair and rebuild.

“This work establishes that damage to aging proteins previously thought to be irreversible can be repaired,” wrote the team. Study author and Revel CEO Aaron Cravens added in a press release: “More work is needed, but these results alter the starting assumption for how we think about this fundamental aspect of the aging process.”

Rusting Away

AGEs are often nicknamed the body’s rust. They coat structural proteins, and like rust eating away at a car, gradually damage them. Scientists discovered AGEs in the 1980s and have sought ways to scrub them away ever since.

Most aging research has focused on keeping cells healthy. The scaffolding surrounding those cells has received far less attention, even though it makes up roughly 70 percent of the body. These structural materials are especially long-lived. It takes the body 15 years to replace half of its collagen, for example. That longevity comes with a price. The longer these proteins stick around, the more likely they’ll incur damage from accumulating AGEs. The result isn’t just loose skin, weakened tendons, and creaky joints. The heart, kidneys, brain, and eyes also suffer.

Scientists have developed drugs to intervene. Some are able to stop new AGEs from forming but fail to clear those already embedded in tissue or restore damaged proteins. Attempts to develop enzymes that could cut them apart have also been unsuccessful, largely because there aren’t obvious natural enzymes in the body to use as a starting point for protein engineering.

The authors of the new study looked outside the body, starting with an unusual idea. Human remains, including AGE-laden proteins, are eventually decomposed by microbes. The team reasoned these bugs may harbor enzymes that can be engineered to clean up the molecular debris while we’re still alive.

Needle in a Haystack

For the search, the team focused on CML, the most abundant type of AGE.

CML is both notoriously stubborn and detrimental to our health. It triggers cells to release inflammatory molecules that stiffen tissues and damage microglia, the brain’s immune cell guardians, contributing to cognitive decline during aging.

“We believe you can remove [CML damage] enzymatically, by going in and developing these lawnmower enzymes that can just cut and clip these changes off of the proteins,” Cravens told The Scientist.

The team screened DNA sequences from over 50,000 microbes with AI and predicted the structures of the enzymes they encoded. They narrowed the candidates by looking for those capable of reaching CML buried within larger proteins like collagen. The winner came from a type of bacteria that thrives in geothermal hot springs.

The enzyme could cleave CML molecules, but barely. To boost its effectiveness, the team turned to directed evolution, a Nobel Prize-winning technique that mimics natural evolution at breakneck speed. After five evolutionary rounds and more than 500 million variants, they landed on CMLase, an engineered enzyme over 10 times more efficient than its ancestor.

To test its activity, the team created CML-laden versions of several proteins, including collagen, retinal proteins, and hemoglobin, which carries oxygen in blood. Initial test-tube experiments showed the enzyme worked as expected. It stripped away the chemical modification and restored the proteins’ original structures, as if they had never reacted with sugar. Think Rust-Oleum, but for damaged proteins.

But does it work in actual tissues?

Mice might seem like the obvious next test, but their short lifespans make them poor models for decades of accumulated molecular damage. Instead, the team tested CMLase on thin slices of donated human tissue.

In aortic tissue—the aorta is the body’s largest blood vessel—from a 75-year-old donor, the enzyme slashed CML by roughly 70 percent, bringing levels down to those seen in a 30-year-old. Skin and eye lens proteins from a 64-year-donor also showed significant reductions.

“We were pretty floored,” said Cravens.

Chemical reversal, however, isn’t the same as tissue rejuvenation. It’s still unknown if stripping away CML can actually restore tissue. But the finding challenges a decades-long assumption this kind of molecular damage can’t be treated. It also highlights long-ignored structural proteins as a crucial part of damage repair during aging, paving the way for new treatments.

An enzyme like CMLase could, in theory, be formulated as eye drops to clear CML from the lens or be used to plump up the skin’s protective barrier or restore hearts and kidneys. It would be especially valuable for people with type 2 Diabetes, who accumulate these compounds faster than usual.

Plenty of roadblocks remain. Safety is a concern. Because CMLase evolved from a bacterial protein, the body could label it foreign and launch immune attacks (especially with repeated doses). The body’s own enzymes could also break it down before it has a chance to work. And the enzymes will have to tunnel through a dense protective biological sheath that surrounds organs to reach their target. Work is underway to improve its activity, stability, and safety.

But the team is already looking beyond CMLase. Engineered enzymes could potentially erase other forms of molecular damage once considered permanent. CML is just one member of the AGE family. If the approach works, other targets could follow and one by one, they might chip away at the molecular scars of time.

The post Designer Enzyme Strips Decades of ‘Rust’ From Aging Human Tissue appeared first on SingularityHub.

Building new enzymes is a labor of love. These proteins are the body’s chemical workhorses, speeding up the reactions that make life possible. Researchers use them in gene editing and synthetic biology, and they’re involved in many medical treatments.

But enzymes are also extremely finicky. Even tiny changes to their structures can jeopardize how well they work. To grow or improve their capabilities, scientists usually begin with a natural enzyme. In a process called directed evolution, they slowly nudge the enzyme towards new versions with tailored properties. The process is tedious, time-consuming, and despite best efforts, it may never yield the desired result.

“Laboratory evolution requires the commitment of time and resources. So what you start with is incredibly important as a major determinant of what you end up with,” said David Liu at the Broad Institute of Harvard and MIT in a press release.

Natural enzymes don’t always make good starting points. During directed evolution, they can collapse and stop working. But upgraded designs could be far more resilient.

Now, Liu and colleagues have redrawn the starting line. As a proof of concept, they redesigned the enzyme behind Botox with the help of a popular AI model to create more stable variants for directed evolution.

The evolved enzymes were far more stable and specific at cutting a protein linked to neurodegeneration compared to enzymes evolved from their natural counterparts. The strategy could expand the universe of designer enzymes, making it possible to target protein sequences that are currently out of reach because no suitable natural enzyme exists.

“The most important finding is that using AI to stabilize natural proteins can provide much better starting points for laboratory protein evolution than what we and other researchers have been using for decades,” said Liu. “This insight could change the way researchers conduct protein evolution.”

Evolutionary Bottleneck

Liu is no stranger to reprogramming proteins. As the pioneer of base editing—an offshoot of CRISPR gene editing that swaps single DNA letters—his team has long pursued enzymes with better stability and precision.

One way researchers do this is by speeding up evolution. Like all proteins, enzymes have evolved over eons. Some copy, repair, or modify DNA. Others convert nutrients into energy, break down toxins and drugs in the liver, or relay messages inside cells.

Researchers have long tried to make enzymes that do even more by evolving them in the lab. Success is largely tied to the number of generations they can produce. The more rounds, the greater the chances of producing the desired results. This is why these experiments are so tedious. Each round takes time and careful monitoring.

In 2011, Liu’s lab reported a system called PACE that could perform dozens of rounds of evolution a day without intervention. The system grows bacteriophages—viruses that infect bacteria—in vessels that are continuously diluted of certain molecules. Only viruses carrying improved proteins survive the selection pressure.

Using PACE, the researchers created more efficient prime editors, highly precise RNA-targeting enzymes, therapeutic antibody fragments, and tiny gene editing “scissor” proteins.

Then they hit a wall. Nearly all of the team’s successes began with natural proteins. These were effective to a point, but their descendants would often lose stability as they evolved.

Proteins work by docking with their targets, called substrates, like keys fitting into locks. But evolving new abilities requires them to mutate, which increases the chances their structures warp. Rather than fitting the intended locks, the resulting altered proteins instead clump together and become useless. Precision can also suffer. Even if enzymes have been evolved to recognize new substrates, they may still unintentionally act on their original targets.

Proteins that become less stable during the process can require additional work to make them usable, wrote the team.

There are a few workarounds. In one such strategy, researchers adds chaperones—these are proteins that help other proteins fold correctly—to buffer the effects of harmful mutations. While this can work, it adds another layer of complexity to an already intricate process. In another method, scientists first evolve a natural enzyme to enhance its stability and then use that version as a starting point. But this costs more time, labor, and frustration.

New Beginning

The team turned to AI. Over the past decade, powerful AI models for biology have emerged that can predict and design protein structures from their underlying molecular sequence alone. One example is ProteinMPNN, developed by Nobel laureate David Baker and colleagues at the University of Washington. The model dreams up new protein sequences that preserve overall structure while altering the underlying building blocks—all in seconds.

Liu’s team reasoned the AI could generate more stable enzymes to kick off directed evolution. To test their theory, they turned to natural botulinum neurotoxin proteases. These molecular scissors paralyze muscles by snipping specific proteins and are the main active component in Botox.

ProteinMPNN generated 58 designs predicted to be more stable. The top three candidates, when produced in E. coli bacteria, were highly soluble, meaning they didn’t aggregate inside cells. Some even had higher activity than their natural counterparts.

The team fed the redesigned enzymes into PACE, evolving them to slice away a mutated region of a protein associated with neuron health. But in diseases such as ALS (Lou Gehrig’s disease), a repetitive stretch expands, causing the protein to clump together and gradually damage neurons. Although the protein is an attractive therapeutic target, naturally occurring enzymes have had limited success cutting the mutant version before it forms toxic aggregates.

Compared with enzymes evolved from natural botulinum neurotoxin, those descended from the AI-redesigned versions were nearly 80 times more efficient at cutting the target protein, and over 56 times more selective for the intended region on the protein. Across three different types of the neurotoxin and multiple substrates, the AI-designed starting points consistently excelled at producing more stable and effective enzymes.

By mathematically mapping their evolutionary paths, the team found the redesigned enzymes tolerated more mutations while gaining new functions. That extra flexibility could open the door to larger reprogramming efforts, such as targeting substrates that lack natural enzymes.

“If you start with a more stable protein, it has more stability to spare, so it can afford larger changes in pursuit of new functions,” said study author Nicholas Krasnow.

The team worked with immortalized human cells for the study, so whether the proteins perform as well in more complex environments remains to be seen. But the work showcases the power of coupling AI and laboratory evolution to rapidly reprogram nature’s molecular machines, endowing them with functions evolution never produced. The team is already applying the strategy to finessing prime editors and other molecular tools.

The post Why Scientists Redesigned the Botox Enzyme With AI appeared first on SingularityHub.

Gene editing is like a molecular meet cute. When protein “scissors” dock onto the intended gene, even a tiny slip—no more than the width of a hydrogen atom—can ruin the connection, and the protein may latch onto similar DNA sequences nearby. In a rom-com, a missed connection means heartbreak; in gene therapy, it can trigger dangerous off-target effects.

Now, AI is playing matchmaker.

In one recent study, researchers used AI to engineer more faithful gene-editing scissors with higher fidelity than previous versions. In another, AI designed the scissors from scratch. Although the synthetic proteins are markedly different than their natural counterparts, they successfully edited genes in cells from multiple species.

The studies expand protein design. “The ability to customize the molecular geometry of genome editors will drive progress towards safer and more efficient therapies,” wrote Hoi Yee Chu and Alan Wong at the University of Hong Kong, who were not involved in either study.

Scientists still need to test the new molecular scissors inside the body. Meanwhile, they’ll continue searching for natural gene editors they can both employ and use to train AI.

Long Road to Precision

There’s no doubt CRISPR has transformed biology.

From blood disorders to inherited blindness and high cholesterol, the gene editor has gone from academic curiosity to a therapeutic powerhouse in just over a decade. Researchers and doctors are also using it to engineer immune cells that recognize and attack once untreatable cancers.

But it’s not all roses: CRISPR doesn’t always edit the right gene.

The gene editor’s protein scissors, called nucleases, are steered to a DNA sequence by a fragment of guide RNA. Once the arrive, the scissors cut the DNA and change the genome.

CRISPR was first used to inactivate target genes. A more sophisticated version, called base editing, can handle single DNA letter swaps. Yet precision is still a hurdle. Early CRISPR was even branded “genetic vandalism” for straying away from its intended target and making unpredictable genome-wide changes. Another problem is called bystander editing. This is when the tool alters neighboring DNA letters that weren’t supposed to be changed. Even a handful of unintended edits could undermine treatment.

Making CRISPR more precise is something of a holy grail. But nucleases are intricate molecular machines, and even small changes to a few critical building blocks can cripple them. To improve the proteins, studies have subtly altered existing nucleases and screened variants to surface versions that have better specificity without sacrificing activity, a tradeoff that has long plagued the field.

Both approaches are tedious and slow. And because they begin with natural enzymes, they explore only a tiny fraction of the protein designs that might actually work.

“What remains unclear is which amino-acid residues [protein building blocks] in Cas9 can be further engineered to maximize fidelity—that is, to ensure that the enzyme cleaves the genome at the correct site and makes the intended edit,” wrote Chu and Wong.

AI Intuition

A Chinese team turned to Google DeepMind’s AlphaFold 3 to open the black box. AlphaFold predicts not only protein shapes but also how proteins interact with DNA, drugs, and other biomolecules.

Most researchers use AlphaFold to CRISPR and its target DNA, revealing potential hotspots for engineering. This team took a different approach. Rather than focusing on a single protein-DNA structure, they used the AI to calculate the likelihood that specific parts of of CRISPRs protein scissors would interact with various DNA sequences.

They first mapped changes to the genome after base editing in human kidney cells and then compared thousands of off-target and on-target changes. To make sense of the data, they developed ContactSeek, an AI that pinpointed protein areas more often associated with mistaken targeting. These would be prime candidates for redesign.

They then used ContactSeek to improve a base editor that switches the DNA letter A to G. With only two changes, the new editor outperformed several existing high-fidelity editors. They also generated more selective CRISPR variants—those that used a different pair of protein scissors—without sacrificing editing efficiency.

Traditional methods often rely on individual trial-and-error experiments. But ContactSeek extracts patterns from thousands of predicted interactions, revealing contact regions that might be hard to detect from single tests. But like other AI models, ContactSeek’s predictions are only as good as the data used to train it. The tool could be further improved with more data and by adding complementary AI tools, such as RoseTTAFoldNA.

In a separate study, CRISPR pioneer Jennifer Doudna and colleagues asked AI to dream up entirely new nucleases. They focused on compact proteins that gave rise to Cas12, the proteins scissors often used in base editing. Instead of tweaking existing proteins, however, they fed an AI model the proteins’ 3D structure, and asked it to redesign them. The AI spooled out thousands of synthetic candidates.

But it didn’t give any hints about which might work, and testing each would be impractical.

Instead, the team trained a second AI on which parts of the proteins interact with each other and which with DNA. Eventually, the second model learned what sections could be changed and homed in on a handful of promising designs. They differed from their natural counterpart sequences by roughly 30 percent, far more than previous AI-designed CRISPR nucleases.

Despite being somewhat alien, several edited genes in bacterial, plant, and human cells. A few even outperformed their natural counterparts in terms of efficiency. Like ContactSeek’s designs, the synthetic nucleases must next prove themselves in the body. Researchers want to make sure they don’t trigger an immune attack and can edit enough cells to treat disease.

Neither study directly addressed bystander editing, another headache in the field. But the tools can work with each other. One fine-tunes nature’s gene editors; the other creates brand new designs. It’s early, but AI is beginning to help design the next generation of gene editing tools.

The post Scientists Are Designing CRISPR Gene Editors With AI appeared first on SingularityHub.

Scientists just transformed a living mouse’s kidney into an incubator for developing human sperm made from blood cells.

It sounds like sci-fi Mad Libs. But a team at the University of Pennsylvania, led by Kotaro Sasaki, pulled it off. For up to nine months, a tiny pouch of human cells nestled beneath a mouse’s kidney gradually developed into immature sperm. The study is the latest in a decade-long quest to grow sperm in the lab.

If successful, lab-grown sperm could open a new window into the earliest stages of sperm development, a process that’s notoriously difficult to study because it begins before birth. The research could also shed light on male infertility—which, in many cases, has no clear cause—and inspire treatments.

More controversially, lab-grown sperm could one day be used to make babies, offering hope to people struggling to conceive and same-sex couples who want to have children genetically related to both parents. That goal is still far off. Though gene activity was similar to their natural counterparts, none of the lab-grown cells were able to develop into functional sperm.

Those results starkly contrast similar attempts in mice. Researchers have already produced functional sperm and egg cells from rodent skin cells, and in two pioneering cases, used them to create healthy pups with two dads. But translating this capability to humans has been difficult, largely because reproductive development differs tons between species.

Still, the new system can help scientists probe the earliest stages of human sperm development. And because any future clinical applications would first need extensive testing in non-human primates, the team also generated immature sperm cells from monkeys, whose reproductive biology more closely mirrors our own.

Recapitulating sperm development in the lab has uses beyond fertility treatment too, such as testing whether drugs interfere with reproduction. The platform “establishes a robust framework for modeling primate germ cell [reproductive cell] development,” the team wrote.

Winning Recipe

For decades, scientist have been able to rewind adult cells into induced pluripotent stem cells (iPSCs). These cells can go on to  become nearly any other cell type. But steering them to become sperm has proven far trickier, largely because human sperm takes years to fully develop.

The journey begins before birth. Early stem cells give rise to spermatogonia, the founder cells that replenish sperm throughout life. These cells are largely dormant until puberty, when some begin meiosis, a special type of cell division that halves their chromosomes. That way, when sperm meets egg, the embryo gains a full genetic set.

But the cells don’t live in a vacuum. Proteins and other molecules instruct immature sperm when to grow, divide, or pause. Physical forces, such as the winding architecture of the testes and the flow of fluid, also play a role. Recreating this intricate environment in a dish has been one of the biggest challenges to the study of sperm development and our ability to grow them in the lab.

Roughly a decade ago, Sasaki and colleagues found a way to transform human iPSCs into early stem cells that could eventually give rise to sperm and egg. On paper, their gene expression profile closely matched that of natural counterparts. But in practice, the cells couldn’t mature further without the right environmental cues.

In an usual workaround, the team next mixed the immature cells with supportive, non-reproductive cells isolated from mice testes. While it was an usual environment, the mice cells provided nutrients and molecular signaling that nudged development forward.

Called xrTestis, the mixture spontaneously organized into tube-like structures resembling those inside testes. “Overall, our culture method accurately recapitulates in vivo human male GC [germ cell] development and allows us to understand the genetic pathways governing this process,” they wrote at the time.

Yet none of the immature sperm advanced beyond developmental stages normally seen in fetuses. And the miniature structure collapsed after 80 days, likely because it lacked a blood supply.

Unexpected Host

To prolong the mixture’s viability and push sperm development further, the team transplanted it into the kidneys of immunodeficient mice.

The graft organized itself into the hallmark tubular structures found in testes within a month and remained stable for at least half a year. The mice showed no signs of discomfort or immune rejection.

Six months later, some human cells developed into spermatogonia—the self-renewing stem cells that eventually generate sperm. Along the way, they underwent a major event: an epigenetic reset. During this process, chemical tags on DNA that influence whether genes are turned on or off are almost completely wiped clean. If that reset is incomplete, it could compromise any sperm eventually used for reproduction.

Here, the team found a “dramatic” genome-wide epigenetic reset. The cells’ gene activity mirrored their natural counterparts. Even though the graft survived for at least nine months, however, none of the cells were able to develop into mature sperm.

This is likely due to the environment. Human and mice testes don’t share the exact same signaling molecules or respond the same way to hormones and other developmental cues. Replacing the mouse support cells with human versions could help the spermatogonia develop further.

The Ultimate Test

The team also tested the technique in monkeys, with results similar to those found in human cells. “While our human iPSC system provided valuable insight into male gametogenesis [the formation of reproductive cells], future studies of fertility competency must be carried out in non-human primates,” they wrote.

Although the cells also halted at the immature stage, the results are still valuable. Previous studies have shown monkey spermatogonia can generate mature sperm after transplantation into recipient testes, opening the door to eventually testing if lab-grown cells can sire healthy offspring.

That idea is precisely what makes some bioethicists uneasy.

Mass-producing sperm and eggs in the lab could generate far more embryos for selection, making it easier for prospective parents to choose desirable traits such as eye color or height. Pairing the technology with gene editing makes “designer babies” less hypothetical. And if skin scrapings or a single hair can be turned into reproductive cells, someone could theoretically create sperm or eggs from another person without consent.

These scenarios are purely speculation, but regulators are already preparing for that future. In 2025, the United Kingdom’s Human Fertilization and Embryology Authority urged the government to explicitly tackle lab-grown reproductive cells in legislation. The International Society for Stem Cell Research has similarly called for careful oversight and public engagement before clinical use. Most countries, however, are only beginning to grapple with how these technologies should be dealt with.

Meanwhile, companies are pressing forward. Paterna Biosciences in Utah recently announced they had produced functional sperm from immature sperm collected during testicular biopsies. According to the company, early embryos created with the lab-grown sperm seemed comparable to those produced through standard in vitro fertilization (IVF). And California startup Conception recently reported generating early human egg cells from iPSCs. Neither company has released results in a preprint or journal article, making the claims hard to evaluate.

Like germline gene editing, conversations weighing the pros and cons of lab-grown reproductive cells will help decide not only what’s possible, but also what should be permitted. For now, the team stresses that their work is only a research tool—not a fertility treatment—and clinical use is a long way off.

The post Scientists Inch Closer to Creating Human Sperm in the Lab appeared first on SingularityHub.

Cancer researchers just found a new way to take on tumors.

CAR T cell therapy revolutionized blood cancer treatment by supercharging a patient’s own immune cells to hunt down cancers. But the approach has struggled in solid cancers. These are some of our top killers—breast, lung, prostate. Roughly two million Americans are expected to be diagnosed with cancer in 2026, and over 600,000 will likely succumb to the disease.

Unlike blood cancers, solid tumors rarely share a single, universal target for CAR T cells. Even cells within the same tumor are a mishmash. Some have little or none of a target protein, allowing them to evade the engineered immune cells, survive treatment, and fuel relapse.

“Target discovery remains a considerable challenge in the development and translation of

CAR T cell therapies for solid tumors,” wrote Christopher Mount and Marcela Maus at the Massachusetts General Brigham Cancer Institute.

Now, two independent teams have converged on the same promising target: A cell-surface protein called GPNMB. In one study, CAR T cells engineered to recognize GPNMB rapidly destroyed glioblastoma—a lethal brain cancer—in tissues taken from patients and shrank tumors in mice.

A second team used a similar strategy against an aggressive soft tissue cancer to fight tumors in organoids and mice. In an early clinical trial involving a single participant, one infusion stabilized the disease for three months without serious side effects.

CAR T designers are often wary of broadly shared targets because they can trigger dangerous attacks on healthy tissue. But GPNMB is an odd duck. In addition to cancer cells, it also sits on immune cells that spur cancer growth or suppress the body’s innate ability to get rid of tumors.

“Our approach attacks both the tumor and the environment that allows it to thrive,” said Sheila Singh at McMaster, who led the glioblastoma study, in a press release. “We’re going beyond targeting the cancer alone and eliminating the immune cells that help shield it from treatment.”

Cancer Fortress

Solid cancers have plenty of tricks to outsmart CAR T cells.

Researchers make these supercharged immune cells  by extracting a patient’s own T cells and genetically engineering them to produce protein “claws” that latch onto a specific cancer target. After infusing the cells back into the body, they seek and destroy tumor cells. CAR T has transformed treatment for several blood cancers and is showing promise in autoimmune diseases and excessive heart and kidney scarring. To simplify the procedure, researchers are also exploring ways to directly transform T cells inside the body with gene therapy.

Solid cancers, however, are far tougher opponents. Unlike blood cancers, which are heavily coated with a shared target called an antigen, solid tumors are molecular patchworks. Cells within the same tumor can display different targets—or none at all—allowing some to evade a CAR T attack and trigger relapse. Many of these targets also appear on healthy tissues, raising the risk of dangerous side effects. And then there’s the tumor microenvironment: A toxic, glue-like “fortress” that hijacks immune cells and uses them to battle incoming CAR T cells.

These barriers aren’t impenetrable. Previous work enlisted  bacteria to help CAR T cells burrow into tumors. Other efforts engineered ultra-sensitive CAR T cells capable of detecting tiny amounts of a cancer target shared across multiple solid tumors.

“Recent reports of activity in several clinical trials reinforce optimism that these efforts may result in true clinical benefit,” wrote Mount and Maus, who were not involved in either study.

But these strategies require additional engineering steps, increasing complexity and cost. And most still leave one major roadblock intact: The tumor’s immune defenses.

One-Two Punch

In the glioblastoma study, the team at McMaster University scoured donated tumors for proteins that distinguished the most aggressive cancer cells. They found one standout: GPNMB. Another test of every protein dotting the cell surface confirmed it as a promising target. The protein is evident across a cancer cell’s membrane, making it readily accessible to CAR T cells.

In lab tests, CAR T cells engineered against GPNMB performed well, nearly eliminating tumors grown from patient samples and extending survival in mice.

The target turned out to be far more valuable than expected. The team soon realized that GPNMB also marked the immune cells that suppress anti-cancer drugs. CAR T cells attacked both fronts simultaneously, weakening the tumor’s immune shield and killing the cancer itself.

“Most approaches have focused on killing cancer cells alone,” said study author Shan Grewal. “Our work suggests we may also need to dismantle the immune support system that helps the tumor survive.”

The second team focused on alveolar soft-part sarcoma, a rare soft-tissue cancer that often spreads to the lungs, brain, and bones before it’s diagnosed. Treatment often comes too late.

The disease is driven by a type of “fusion” gene created when pieces of genetic material are accidentally stitched together. These genes are extremely tough to target directly. Instead, the team screened all surface proteins on the cancer cells and again landed on GPNMB as a top candidate for intervention. The protein’s levels closely tracked the activity of the fusion gene.

CAR T cells targeting GPNMB cleared tumors and prevented metastasis in mice. But because an earlier antibody drug against the protein caused severe skin toxicity in patients, the team also tested their CAR T cells in mice carrying small human skin grafts. Although inflammation initially flared, there were no signs of ongoing skin damage.

Encouraged, the team treated a patient with relapsed, metastasized alveolar soft-part sarcoma. After a single infusion, the engineered cells rapidly divided in the bloodstream and remained detectable for roughly a month. The treatment didn’t trigger skin rashes or more dangerous side effects, like cytokine release syndrome where the body mounts a hyperactive immune defense that harms healthy organs.

The treatment’s benefits outlasted the engineered cells themselves. For roughly three months, imaging tests found fewer of the small, round spots on the patient’s lungs that often signal metastatic cancer, suggesting the disease had stabilized.

A final analysis identified another roadblock: Clusters of cells that suppress the immune system and could blunt the benefits. Adding drugs to block these immune molecules boosted tumor killing in mice. Because the same kind of gene fusion drives other cancers, including kidney, the CAR T cells could have reach beyond this specific type of sarcoma.

Together, the studies underscore that the best CAR T targets might extend beyond cancer cells to expose and attack cancer’s immune cell supporters too. Finding a viable target is a delicate balancing act. Chosen well, and CAR T cells could tackle multiple drivers for cancer growth. Choose poorly, and healthy tissues could get hurt in the crossfire.

Even so, “these two studies indicate that GPNMB represents an actionable target for CAR T cell therapies in several solid tumors,” wrote Mount and Maus.

The post CAR T Revolutionized How We Treat Blood Cancers. Now It’s Closing In on Solid Tumors. appeared first on SingularityHub.

Synthetic biologists have long dreamed of constructing artificial cells from the bottom up. Researchers have now taken a major step in this direction by demonstrating that non-living components can be assembled into a system that grows, copies its DNA, and divides.

The genomic revolution transformed our ability to understand and manipulate cellular machinery, allowing scientists to rewire cells’ genetic circuitry to fight disease, produce valuable chemicals, and make crops more resilient. The holy grail for the field, however, has been to use these tools to create entirely synthetic cells—a milestone that would signal humanity’s mastery of life’s key ingredients.

How best to do this has long been an open question. Genomics pioneer Craig Venter made significant progress by stripping living bacteria back to their bare essentials, culminating in the 2016 unveiling of a minimal cell with just 473 genes. The Synthetic Yeast Genome Project has taken the opposite approach, building artificial versions of all 16 yeast chromosomes from scratch, though they’ve yet to get them working together in a single cell.

Now, researchers from the University of Minnesota, have assembled a synthetic cell out of engineered, non-living components housed inside an artificial, cell-like membrane. Their creation was capable of the four hallmarks of a living entity—the ability to feed, grow, copy genetic material, and produce offspring.

“We’ve replicated in chemistry what only used to be possible in biology: the complete set of behaviors of a cell,” Kate Adamala, who led the project, said in a press release. “It proves that the most fundamental functions of life, like growth and replication, do not need a mysterious magical spark.”

The researchers outline the design for their synthetic organism—nicknamed SpudCell for its potato-like shape under the microscope—in a non-peer reviewed paper uploaded to bioRxiv. SpudCell features a genome 90,000 base pairs long, which is considerably smaller than the 113,000 base pairs researchers had previously predicted would be the bare minimum needed to support a viable cell.

Rather than housing all the genes in a single chromosome, the team split them across several small, circular DNA molecules called plasmids, each specialized to fulfill specific functions. The researchers say this makes it possible to modify different aspects of the organism more easily.

To read the genome and build proteins, SpudCell uses a pre-defined kit of 36 purified enzymes drawn largely from E. coli. The whole assembly sits inside a liposome, a hollow bubble of the same fatty molecules that form natural cell membranes.

The artificial cell feeds in two distinct ways. Small molecules pass directly into the cell through protein pores implanted across the membrane. Molecules too large to squeeze through—like ribosomes and enzymes—are packaged inside tiny lipid bubbles that fuse with the membrane and empty their contents inside.

While the cell can feed, it’s entirely reliant on the researchers providing it with specially prepared meals. This means it’s a long way from surviving in the wild, which is both a major limitation and a key safety mechanism. “It’s a bed-ridden Frankenstein’s monster that has to be spoon-fed,” Adamala told New Scientist. “There’s no danger of it running amok.”

After ingesting “food,” SpudCell’s genes use the material to churn out proteins, while folding the incoming lipids into its membrane. This causes the whole cell structure to swell. Within a few hours, it’s bulked up enough to reproduce by dividing into two smaller cells.

Replicating cell division has been a longstanding challenge in the field. Natural cells split using an intricate protein scaffold called a cytoskeleton that’s fiendishly difficult to recreate. Adamala’s team sidestepped this problem by using a completely different mechanism, in which proteins bunch up on the membrane’s surface, putting it under mechanical strain. Eventually this squeezes two parts of the membrane together to pinch off a new cell.

The cells even manage a crude form of evolution. When the researchers introduced a genetic tweak boosting the cells’ ability to feed, those with the variant outcompeted the original lineage within five generations, and their edge widened when the researchers exposed the population to nutrient scarcity.

However, no one is claiming SpudCell is alive. Crucially, the cells cannot make their own ribosomes—the machines that build proteins from genetic instructions—and the ribosomes provided by the researchers degrade over time, limiting the cells to five to ten divisions.

The University of Chicago’s Jack Szostak told Quanta the work is an “impressive step” but the inability to produce ribosomes seriously limits potential for sustained growth. “If their system was able to generate its own ribosomes and other proteins and RNAs, it would be much closer to existing biological cells such as bacteria,” he said.

Nonetheless, the researchers think these artificial cells are a promising way to manufacture drugs, fuels, and materials without the toxic, energy-hungry industrial chemistry we rely on today. And they’ve created a new nonprofit called Biotic to share the tools they’ve developed with researchers.

The post This Synthetic Cell Grows, Copies Its DNA, and Produces Offspring—But It Isn’t Alive appeared first on SingularityHub.

Researchers at the University of Cambridge have developed what they describe as a fundamentally new type of vaccine using artificial intelligence. The vaccine’s key component was designed entirely by AI and has now been tested in people for the first time.

The goal is ambitious: a single vaccine that works not just against all known human coronavirus variants, but against related bat viruses that could jump from animals to humans and cause future pandemics.

Traditional vaccines train our immune system to recognize one specific virus. The problem is that viruses mutate. When they change enough, the vaccine stops working, which is why we need a new flu shot every year and why Covid vaccines have been updated repeatedly since 2021.

AI offers a way around this. By analyzing genetic data from thousands of related viruses, it can identify the parts that stay the same across different strains and that are unlikely to change over time. Target those stable features, and you have a vaccine that should work against the whole family, not just the strain you started with.

This is exactly what the Cambridge team did. They used AI to scan viruses from the sarbecovirus family, which includes the viruses that cause both SARS and Covid, as well as a range of animal coronaviruses—looking for shared features that evolution has left largely untouched. Those features became the basis of the vaccine.

DNA Vaccines

While many people are familiar with the mRNA shots used during the pandemic, this new vaccine uses DNA. DNA vaccines are generally more stable than mRNA vaccines, making them easier to store and transport. This is a significant advantage in lower-income countries where “cold-chain” infrastructure is limited.

They can also be administered without needles. A high-pressure stream of liquid delivers the vaccine through the skin, making administration less painful and easier to scale up during an outbreak.

Could It Protect Against Future Pandemics?

These practical advantages matter most if the vaccine itself can do something no existing jab can: protect against viruses we haven’t encountered yet.

Broad-spectrum vaccines could change the way the world responds to emerging infectious diseases. By offering much wider protection than traditional vaccines, they could provide rapid immunity against new and emerging viral threats. This would equip public health officials with tools to stop future outbreaks in their tracks before they have a chance to turn into global pandemics.

They could also transform our approach to more familiar diseases. Influenza is a prime target because it exists in many different strains and evolves so rapidly. Scientists have to predict which strains will dominate each flu season, and if they guess wrong, vaccine effectiveness can suffer. A universal flu vaccine that targets features shared across multiple strains could eventually end the annual race to keep up with the virus.

The Ebola virus shows why this matters right now. The recent outbreak in the Democratic Republic of the Congo and Uganda is driven by the Bundibugyo strain, which bypasses existing vaccines. While researchers rush to create a new vaccine specifically for this strain, local communities remain at high risk. A broad-spectrum vaccine designed to cover an entire virus family could transform that picture.

What the Trial Found

This is the first human trial of an AI-designed vaccine. The results showed that this DNA vaccine was able to stimulate the immune system to produce antibodies that can recognize different types of sarbecoviruses. The technology was found to be safe and well tolerated.

This is an exciting advance because it demonstrates how AI has the potential to design variant-proof vaccines against future pandemic threats. The needle-free delivery system could also make the vaccine easier to administer and distribute worldwide.

However, there is more work to do. Although the results in this study are encouraging, the immune responses following vaccination were modest. It was also uncertain how long the protection lasts and whether further boosters will be required. Larger trials are also needed to determine whether the vaccine can prevent or reduce viral infections in the real world.

A universal vaccine remains a few years away. And any new vaccine must still pass larger trials to prove it is safe, effective, and provides lasting protection. But this study shows the goal is getting closer—and AI may help us get there faster.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The post The First AI‑Designed Vaccine Has Been Tested in People. Here’s What Happened. appeared first on SingularityHub.

A handful of healthy senior citizens are about to trip on psilocybin—to see if the psychedelic protects aging brains.

Psilocybin, the active ingredient in magic mushrooms, is best known for its ties to 1960s counterculture. But now it may also herald a new genre of mental health treatment. From severe depression to post-traumatic stress disorder, studies have highlighted psychedelic drugs’ ability to reshape brain networks and relieve debilitating symptoms.

Most of these studies have focused on younger people with mental health conditions that don’t respond to standard treatment. The field’s success is prompting scientists to ask if psychedelics could also help healthy brains age better.

A team from the UC Berkeley Center for the Science of Psychedelics is about to find out. In a first-of-its-kind study focused on adults between the ages of 60 and 85, they’ll investigate how psilocybin affects perception, emotion, and memory using a battery of psychological tests.

Multiple scans before and after dosing will track changes in the brain. And detailed surveys will gauge broader shifts in well-being: Do participants feel more “in tune” with their emotions, feel less isolated, or experience a renewed sense of wonder about the world?

“What really excites me is that we’re focused on healthy older adults,”  said Tyler Toueg, who co-led the study’s design, in a press release. “Most clinical trials with older adults are focused on people who already have a diagnosis. We’re asking whether we can actually promote positive outcomes in older adults who are healthy.”

Called PLASTICITY, the trial could also open a rare window into how a psychedelic experience reshapes healthy brain networks. And because the drug alters our sense of self, psilocybin could help researchers probe the ways in which the brain constructs reality.

“I’m very interested in psilocybin as a potential mental health treatment, but I’m also interested in it as a way to shed light on these central mysteries in neuroscience and psychology,” said study designer Michael Silver.

Chasing the White Rabbit

Psychedelic research was highly restricted for decades. But advocates, including the non-profit Multidisciplinary Association for Psychedelic Studies, have steadily pushed to reopen the field, arguing that these drugs might keep mental health symptoms at bay.

Early results helped usher psychedelics into the mainstream. In 2023, a randomized, placebo-controlled trial found that a single dose of psilocybin, paired with therapy, eased depression. Oregon later approved supervised psilocybin therapy—though the drug remains federally illegal in the US—and Australia became the first country to greenlight it for depression and post-traumatic stress disorder. More recently, two late-stage studies reported strong effects in severe depression, potentially paving the way for FDA approval.

Scientists still don’t fully understand how psilocybin works in the brain. But there are hints. The drug appears to rapidly reorganize the connections between brain cells, particularly in the hippocampus, a region of the brain central to learning, memory, and navigation.

Neurons constantly change their connections in a process called plasticity that encodes experiences into neural networks, allowing the brain to process information, learn, and lock in memories. In youth, these connections are flexible and expansive. But with age and in conditions like depression, the brain’s flexibility wanes.

The birth of new neurons, or neurogenesis, also contributes to plasticity. Neurogenesis only occurs in two brain regions, one of which is the hippocampus. Although whether it actually takes place in humans is controversial, it is strongly linked to learning, memory, and emotion, and it declines in both psychiatric disorders and aging.

Psilocybin may reset brain plasticity to a more youthful state.

In rats modeling depression, for example, a study showed the drug shifted dark moods into behavior that was more exploratory and engaging. Where traditional antidepressants, like Prozac, tend to blunt symptoms, psilocybin seems to overwrite entrenched negative patterns. This suggests deeper circuit-level changes.

In another study, the drug reopened a critical window for learning in mice. During adolescence, the brain is highly plastic, but it begins to stiffen in adulthood. Psilocybin temporarily restored malleability and changed the mice’s social behavior. In some brain regions, the drug increased sensitivity to oxytocin, the so-called “love hormone.” The authors suggested the drug induced a state called metaplasticity, in which neurons are more likely to respond to oxytocin and other regulators to rewire, form new connections, and grow their branches.

Psilocybin’s effects may extend beyond the brain. Depression, chronic stress, and the immune system are tightly linked. In a third study, researchers identified a brain-spleen connection that drives fear and anxiety. Psilocybin suppressed inflammatory immune cells associated with brain inflammation and dampened anxiety-like behavior in stressed mice, even under threat.

Both effects—dialing up plasticity and lowering inflammation—make psilocybin an intriguing way to potentially counter changes in the aging brain.

“We know that with age, we lose synaptic connections, especially in certain brain regions like the hippocampus and prefrontal cortex,” said Toueg. “There’s a lot of overlap between the mental states that psychedelics influence and those associated with successful aging.”

Tomorrow Never Knows

The PLASTICITY trial is designed to test whether psilocybin can produce lasting changes in neuroplasticity in healthy adults aged 60 to 85. Participants will first undergo assessments of cognition, visual perception, and brain structure using advanced MRI techniques.

Diffusion MRI scans will focus on the hippocampus to capture microscopic changes in its structure. Functional MRI will focus on brain activity as participants perform learning and memory tasks, offering a dynamic view of how activity shifts after dosing.

The study will also see if psilocybin increases vagus nerve activity, which has been linked to better stress recovery. Participants will complete detailed surveys about the experience ranging from emotional responses, like wonder, to potential shifts in outlook and social cognition.

“Things like depression, anxiety, stress and rumination are all associated with worse aging outcomes,” said Toueg. “Things like having purpose in life, emotional regulation, and awe are all associated with more successful aging.”

The trial began enrolling participants in November last year. Two volunteers have already completed the tests, and the team aims to dose 20 people by the end of 2026.

Although psilocybin trials are now widespread, older adults remain underrepresented. One estimate suggests just 1.4 percent of participants are 65 or older, despite potentially being among those most likely to benefit from interventions that enhance plasticity.

“This study allows us to directly test whether the promising findings from animal models translate to older humans and to generate data that will inform future research on aging, cognition, and mental health,” said Silver.

Toueg agrees. “I think that no matter what we find, this study will have implications for how we think about intervening in the aging brain,” he said.

The post Can Psychedelics Reboot Aging Brains? We’re About to Find Out appeared first on SingularityHub.

Scientists at Columbia University have used a precise gene-editing tool, base editing, to make changes in three disease-linked genes in early-stage human embryos. The goal wasn’t to create pregnancies, but to test the safety and limits of rewriting DNA at the very early stages of life.

The paper, not yet peer reviewed, sparked immediate controversy. Some researchers hailed it as a technical milestone that could one day prevent devastating inherited diseases before birth. Others warned it edges society closer to the prospect of “designer babies”—an idea bioethicists have argued is akin to modern eugenics.

The debate is hardly hypothetical. The work has already attracted commercial interest. New York-based Nucleus Genomics, which screens in vitro fertilization (IVF) embryos for serious genetic disorders, has also developed predictive models for complex traits such as intelligence. The company plans to sponsor future research by study leader Dieter Egli and team.

Critics worry that even experimental advances could fuel demand from wealthy patients while encouraging companies to develop and market embryo-editing technologies, despite unresolved ethical and safety concerns.

Egli argues the findings should be public precisely because these debates are no longer academic curiosity. He has repeatedly called for scientists, regulators, and the public to weigh the pros and cons of editing human embryos. As for clinical use today, his position is unequivocal: “You can’t use it. It’s as clear as day and night,” he told Nature.

Conceptual Shift

Why edit embryos at all?

Cells in an early embryo eventually give rise to every tissue in the body. Correct a harmful mutation at the start of development, and the fix could, in theory, propagate throughout a child’s entire body—and even be passed on to future generations.

The strategy could help in genetic disorders that hamper fetal development or trigger diseases in newborns. For some developmental and metabolic conditions, intervention after birth may already be too late. Even when treatment is possible, gene editors must be able to target various organs, which is an ongoing challenge.

In various efforts, scientists have already repaired disease-causing mutations in mouse embryos and fetuses, including those linked to blood disorders. But mice aren’t humans. Early embryos from the two species repair DNA damage in fundamentally different ways, making it tough to gauge whether a strategy that works in mice will succeed, or prove safe, in people. That uncertainty has fueled interest in testing gene-editing tools directly in human embryos.

Not everyone is on board. International scientific groups have repeatedly called for a temporary ban on editing human embryos, and the practice is illegal in several countries.

That didn’t stop Chinese scientist He Jiankui. In 2018, he announced the birth of gene-edited babies after using a tool called CRISPR-Cas9, claiming the changes would protect them against HIV infection. Global outrage ensued.

By then, years of research had already highlighted CRISPR’s risk. The tool cuts both strands of DNA and relies on the body’s repair machinery to stitch them back together. But the process can go awry, introducing unintended mutations, deleting large chunks of DNA, or altering the wrong locations on the DNA strands altogether. He’s reckless experiment resulted in three years of imprisonment, although he still defends the work.

Subsequent studies only deepened concerns. In some cases, CRISPR editing in human embryos caused extensive genetic damage. In one study,  it completely destroyed the chromosome that housed the target gene.

An Imperfect Upgrade

The new study tested a next-generation gene editor designed to overcome some of CRISPR’s biggest shortcomings.

Egli and team used an approach called base editing, which rewrites individual DNA letters. Unlike CRISPR, base editing only nicks the DNA strands and is generally thought to be more precise. The technology hit a major milestone last year when it helped cure a baby with a potentially fatal genetic disorder, and earlier lab studies hinted it could also succeed in human embryos.

Working with early-stage embryos, the team edited three genes with the potential to cause illness. In each case, they converted the genetic letter A to G at precise locations. One of the genes, PCSK9, regulates “bad” cholesterol levels. Mutations are associated with a high risk of heart problems. The team’s edit was designed to switch off the gene, mirroring strategies already being explored in adults.

The other two targets, HBG1 and HBG2, control production of fetal hemoglobin, an oxygen-carrying protein. The edits made here reflected a natural protective variant that could lessen symptoms in blood disorders, such as sickle cell disease and beta thalassemia.

The team found no signs of widespread DNA damage, suggesting the tool is more precise than CRISPR. But it wasn’t perfect. Many embryos emerged as so-called genetic mosaics, with some cells carrying the intended edit and others retaining their original genetic blueprint.

That’s a huge problem. As an embryo develops, unedited cells could outcompete edited ones, leaving the disease-causing mutation largely intact. In some embryos, edited cells stopped dividing altogether.

And a lack of obvious chromosome damage doesn’t guarantee safety. The edits could still trigger harmful effects that aren’t noticeable until after birth—when it’s already too late to reverse them.

Calls for Scrutiny

Egli stresses that embryo editing is still far from being ready for the clinic. “These base editors—they can have damaging effects on the embryo. So why would you use it if you don’t fully understand that?” he told Nature.

His team is now working to reduce mosaicism and plans to test the technology in embryos that have developed to roughly 100 cells. This is when fertility clinics typically evaluate and freeze embryos.

Speaking to The New York Times, fertility expert Paula Amato at Oregon Health & Science University, who was not involved in the work, called the strategy “promising.” Genomics researcher Greg Neely at the University of Sydney in Australia also praised the work: “This will go down in history in a positive way—less reckless, more careful and ethical than previous attempts.”

Others remain deeply skeptical. Critics argue that embryo editing permanently alters the genetic inheritance of future generations, who have no say in the decision. The study’s ties to Nucleus Genomics also raised eyebrows. The company previously drew controversy for developing genetic predictions for traits such as intelligence and height and for its slogan “have your best baby.”

To Kian Sadeghi, CEO and cofounder of Nucleus, embryo editing extends that vision. The technology could help couples carrying mutations who struggle to produce enough unaffected embryos for selection during IVF.

Fyodor Urnov at the University of California, Berkeley, who was not involved in the study, isn’t convinced. IVF clinics already screen embryos for many inherited disorders without altering their DNA. Given the risks, selecting an unaffected embryo is often a safer option than rewriting its genome.

“In practical terms, therefore, this preprint will solely impact the rapidly growing movement of embryo editors for purposes of ‘baby improvement’,” he said.

That movement, once taboo, is gaining steam. Yet the traits most often cited by proponents—height, intelligence, emotional regulation—are shaped by hundreds or even thousands of genes, which scientists still don’t fully understand. Such enhancements are far beyond the reach of today’s technology. Every additional edit also increases the chance of unintended consequences.

For Egli, that’s precisely why the research should be discussed openly. “Research is necessary to provide information to discourage the wrong use of a technology,” he said.

The post Precise Gene Editing in Early Human Embryos Reignites the ‘Designer Baby’ Debate appeared first on SingularityHub.

For decades, a handful of molecular switches has haunted the nightmares of cancer researchers. The switches trigger runaway tumor growth and cause the disease to spread across the body in multiple cancers. In theory, this makes them perfect treatment targets. Blocking even one could lead to drugs that are effective against a variety of cancers.

But despite considerable efforts, these switches—all of which are proteins—have escaped our most advanced cancer treatments, earning them the term “undruggable.” This is largely due to a shared trait: They all have smooth surfaces, making it difficult for drugs to interact with them.

But maybe not for much longer.

Researchers recently reported promising results for a new medication targeting a family of undruggable proteins in a clinical trial for advanced pancreatic cancer. The drug, daraxonrasib, nearly doubled survival time compared to chemotherapy, with fewer side effects. It’s not a total cure. But the treatment gives patients precious time, adding roughly 13 months after diagnosis. Patients also reported less pain and better quality of life.

Daraxonrasib is the latest in a new generation of drugs aimed at undruggable proteins. And AI-based tools are now poised to further accelerate progress in the field.

RAS Attack

The RAS family was the first group of oncogenes—or genes that drive cancer—ever discovered. The genes became a major focus in 1982 when several teams independently showed the mutation of a single DNA letter could transform RAS genes into a potent cancer trigger.

The proteins RAS genes encode are like spring-loaded molecular switches that relay signals from a cell’s surroundings. When proteins called growth factors latch onto a cell, RAS switches flip on to promote cell growth and survival, while built-in safeguards quickly turn them off again.

Cancerous mutations break this cycle. The switches get stuck in the “on” position, continuously instructing cells to grow and divide. This is, of course, a hallmark of cancer.

An ideal drug would simply switch RAS off. But most drugs are like rock climbers. They need grooves, pockets, or bumps on a protein to grab onto. Similar to a smooth rock face, RAS offers few such features. Making matters worse, different mutations subtly reshape the protein, so it’s tough to build a one-size-fits-all inhibitor.

The first RAS drug wasn’t approved in the US until 2021, nearly four decades after discovering the genes’ role in cancer. Even then, the drug targeted just one family member of three, limiting its reach to a relatively small group of patients. Many eventually developed resistance.

That’s why daraxonrasib turned heads. Developed by Revolution Medicines in Redwood City, California, the drugs switches off all three RAS family members. Rather than trying to grip the slippery proteins directly, it binds to a partner molecule that helps RAS proteins fold into their final 3D shapes. In this way, the drug hitches a ride on active RAS and shuts the proteins down.

The workaround paid off. The new study enrolled 500 people worldwide with advanced pancreatic cancer. All participants had already tried cancer therapies with limited success. On average, patients receiving daraxonrasib lived 13.2 months and spent most of that time with limited pain. The most common discomfort was a rash. Those receiving chemotherapy fared worse, living roughly 6.6 months and experienced more severe side effects.

The results don’t rival the dramatic success of CAR T cell therapies in blood cancer. In CAR T, caregivers engineer a patient’s own immune cells to recognize and attack tumors, sometimes producing long-lasting remission after a single infusion.

But the findings have energized the field. If approved, a daily daraxonrasib pill would likely be far more affordable and easier to administer than a personalized cell therapy. And because RAS mutations fuel many solid cancers—which CAR T still struggles to control—the drug could offer a new defense against deadly cancers that are largely beyond cell therapy’s reach. Combining daraxonrasib with earlier-generation RAS inhibitors may further boost its effects.

The Genome Guardian

Daraxonrasib didn’t appear overnight. Scientists used a crystallized snapshot of its target protein as a molecular blueprint. Years of medicinal chemistry followed, with scientists repeatedly tweaking candidate compounds to boost potency, improve selectivity, and minimize toxicity.

AI could dramatically accelerate similar efforts against other undruggable cancer targets. Among the most coveted is p53, often called the “guardian of the genome” for its dizzying array of roles. The protein orchestrates the activity of over 300 genes involved in DNA repair, metabolism, cell death, and inflammation, making it one of the cell’s most important defense systems.

Since its discovery in 1979, p53 has been both a holy grail and a headache for cancer researchers. Mutations in the gene are common in multiple cancers. But like RAS, the protein is flat and smooth. Some mutations destabilize its structure; others turn it into misfolded clumps. A universal p53 drug has remained elusive.

Some researchers are trying to restore the protein. In a small trial earlier this year, they tested a drug that restabilizes a common mutant form of p53. Within 21 days, tumors shrank roughly 20 percent in patients with ovarian, breast, and several other solid cancers.

Other researchers aim to selectively kill cells carrying the mutation. Using AI, a team at Baylor College of Medicine screened nearly 10 million compounds that cause mutated p53 cells to self-destruct, while sparing healthy cells. The search uncovered 83 chemically distinct candidates. One called H3 dramatically suppressed tumor growth in mice.

“These results highlight the potential use of AI-powered drug screening to investigate individual p53 mutants in the future,” they wrote. Although the approach is early-stage and only focused on one mutation, the team is hopeful it can be extended to other cancerous mutations.

Most Wanted

MYC is another formerly undruggable protein that could now be vulnerable. Roughly 70 percent of cancers have abnormal MYC activity. Normally, the protein is a master regulator of growth, directing cells to manufacture proteins, replicate DNA, absorb nutrients, and divide when needed.

Cancer finds many ways to hijack the system and keep cells in a state of runaway growth. MYC gene mutations aren’t just single-letter swaps. Sometimes the gene duplicates or is rearranged across the genome, churning out excessive amounts of the protein it encodes. This genetic diversity makes approaches using gene therapy difficult. And again, like RAS, the MYC protein’s smooth, featureless surface lacks stable anchors for drugs.

An emerging strategy is to disrupt MYC’s interaction with other proteins that it needs to function. A designer protein blocking MYC activity, for example, recently showed promise in a small trial against solid cancers. Other teams are using AI to identify drugs that limit MYC’s ability to fix damaged DNA in tumors, kneecapping their ability to divide. Meanwhile, biotechnology companies are deploying AI to map out MYC’s structure and molecular interactions in search of new ways to shut the protein down.

Daraxonrasib’s success shows that undruggable proteins aren’t untouchable. There’s a lot more work ahead to prove other similar drugs can work too. But scientists are increasingly leaning into AI during all stages of drug development to speed up the process. Maybe, one day, “undruggable” will disappear from our vocabulary altogether.

The post After Decades of Failure, ‘Undruggable’ Cancers Begin to Give Way appeared first on SingularityHub.

There’s truth to the old adage, “Age is just a number.” People of the same age differ vastly in health and mental capabilities. One 80-year-old may be vibe coding with Claude, while another is gradually forgetting familiar faces and memories.

To better gauge this difference, scientists have been developing “clocks” that measure biological age. Rather than the number of candles on a birthday cake, these tools capture health at the cellular level and are remarkably accurate at estimating disease risk and even life expectancy. But how they work is hard to explain.

Now Harvard scientists and collaborators have released a powerful and more interpretable clock. Using the gene activity of thousands of individuals and animals, the clock predicts biological age in rodents, monkeys, and humans, including how many years they have left.

The analysis involved over 11,000 gene activity profiles across four species, highlighted shared mechanisms during aging, and responded to known anti-aging interventions—such as parabiosis, during which aging animals receive blood from a young donor.

Although the clock isn’t ready for clinical use, it is a boon to scientists working to slow or even reverse the unstoppable progression of time. It “could help researchers to pinpoint which processes are modulated by interventions or diseases,” wrote João Pedro de Magalhães at the University of Birmingham, who was not involved in the work.

Tick, Tock

Biological clocks come in a variety of flavors.

Most rely on AI to make sense of information held in large databases of people. One of these, for example, uses blood proteins related to brain aging to reflect cognition and its decline better than chronological age. Another type, metabolomic age clocks, sorts through protein and fatty acid building blocks to estimate biological age. These clocks correlate well with risk of inflammation, chronic disease, and frailty (where the body struggles to recover from a mild infection or minor fall). More recent multi-omics clocks combine blood measures, metabolism, gene activity, and clinical data for a comprehensive bird’s-eye view of biological age.

But epigenetic clocks remain the field’s defining breakthrough.

As we age, chemical tags accumulate on DNA, switching genes on or off. The pattern of these tags shifts over time and is shaped by everyday life—diet, exercise, stress, sleep quality. Studies have found that the age gaps between biological and lived years measured by the well-known Horvath epigenetic clock, which relies on DNA methylation, were associated with the risk of various types of diseases. Later versions of the Horvath clock could predict maximum lifespan. And other groups have developed “pan-mammalian” epigenetic clocks that work across species.

“One drawback of epigenetic clocks, however, is their limited interpretability,” wrote Magalhães. “The mechanisms that underpin age-related methylation changes are still debated.”

Clocking In

In the new study, the team measured aging by looking at gene activity, or transcriptomics. Transcriptome profiles capture which genes are switched on at any given moment.

Previous studies have linked the aging transcriptome to chronic inflammation, faltering mitochondria, and the gradual breakdown of the extracellular matrix, the molecular scaffolding that supports tissues and organs. With age, these systems go awry.

“Because the signatures reflect changes in the activity of specific genes, transcriptomic biomarkers are more interpretable than are epigenetic ones,” wrote Magalhães. The tradeoff is that gene activity is far more dynamic than DNA methylation, the epigenetic signature used in the Horvath clock. A transcriptome can shift in response to stress, illness, exercise, or even the time of day, making it a less reliable measure of aging.

To make the new clock, the team assembled over 11,000 transcriptomes, heavily relying on data from the Interventions Testing Program, a giant effort to study longevity treatments in mice. The dataset included mice exposed to genetic tweaks, drugs, and dietary therapies known to affect aging and lifespan. The team also added more than 2,600 samples from monkeys, several hundred from rats, and over 4,000 from humans to deliver a cross-species view of aging.

They then built multiple transcriptome clocks that estimated age and mortality risk. To validate the clocks, they turned to an independent dataset that included rodent models of accelerated aging, Alzheimer’s diseases, chronic kidney disease, and other age-related conditions. When applied to individual cells, the clocks yielded older transcriptomic ages in more than 90 percent of the samples, suggesting that aging is deeply rooted at the cellular level.

In humans, the clocks accurately predicted the lifespans of participants enrolled in a large heart health study. They were also sensitive to environmental factors that affect aging, ticking forward after exposure to radiation or chronic diseases and rewinding after treatments such as young-blood transfusion, a strategy shown to rejuvenate elderly rodents.

An analysis of the genes driving the clocks highlighted many of the usual molecular suspects. Aging turned on genes involved in inflammation, cellular energy disfunction, and senescence—where failing cells leak toxic molecules. Many of these signatures appeared across organs and species, suggesting that core aspects of aging have been conserved in mammals.

These findings are especially valuable for longevity researchers, who often work with rodent models. Despite living a fraction of a human lifespan, aging rodents undergo transcriptomic shifts similar to those found in us. The new clock could easily test their biological age after potential anti-aging treatments, capture the immediate effects, and predict lifespan, long before they die. It could, in theory, speed up aging research and the quest for treatments.

But to be clear, like other aging clocks, it isn’t a crystal ball. Scientists don’t know if the transcriptome changes drive aging or merely reflect its aftermath. The signatures could be capturing overall health and resilience, rather than molecular changes associated with aging per se.

That distinction matters. As we grow older, cells activate a variety of protective genes to counter rising stress, inflammation, and damage. Not every age-related transcriptomic change is harmful. Some changes reflect the body’s attempt to fight back. Because transcriptomes capture only a snapshot in time, scientists still need to differentiate genes that contribute to aging from those that help defend against it and learn how those patterns shift over time.

There’s a broader challenge too. Researchers are building more and more biological clocks using different criteria, and they don’t always agree. One may say you’re far older than another. This highlights “the need for any aging biomarker to be validated carefully,” wrote Magalhães.

The post How Fast Are You Aging? New Genetic Clock May Have the Answer appeared first on SingularityHub.