Gilead Sciences has agreed to acquire German-based Tubulis for up to $5 billion, the companies said today, in a deal designed to expand the buyer’s antibody–drug conjugate (ADC) capabilities with a focus on fighting cancer.
Headquartered in Munich, privately held Tubulis has developed next-generation ADC candidates based on its own conjugation, linker and payload technologies intended to more selectively deliver diverse payloads to tumors deemed to be of high unmet need. The companies said Tubulis’ programs and platforms have broad potential across multiple tumor types, complementing Gilead’s development and commercialization expertise in oncology.
“We like the strategic fit and deal terms of the Tubulis (private) acquisition,” Daina M. Graybosch, PhD, senior managing director, immuno-oncology and a senior research analyst at Leerink Partners, wrote this morning in a research note. “This is more than an oncology bolt-on; we see real platform value in application of Tubulis’ ADC technologies to other therapeutic areas, namely virology.”
Tubulis’ lead pipeline candidate, TUB-040, is a sodium-dependent phosphate transport protein 2B (NaPi2b)-targeting topoisomerase-I inhibitor (TOPO1i) ADC that is now under study in the Phase Ib/II NAPISTAR1-01 trial (NCT06303505) assessing its safety, pharmacokinetics, and preliminary efficacy as a treatment for platinum-resistant ovarian cancer and non-small cell lung cancer (NSCLC).
In October at the European Society for Medical Oncology (ESMO), Graybosch noted, Tubulis presented data for TUB-040 showing a confirmed 50% overall response rate (ORR) and a 60% unconfirmed ORR across dose levels and irrespective of target antigen—results that were competitive with more mature datasets from leading TOPO1i ADCs.
“Though the dataset was early, and our primary outgoing question was how durability would mature, we suspect that Gilead saw durability maturing positively in their diligence,” Graybosch added. “If TUB-040 proves active in NSCLC, the program could complement their Trodelvy and IO [immune-oncology] lung programs. We wonder if Gilead saw early clinical NSCLC data in their diligence and if excitement around the emerging signal drove some of Tubulis’ valuation.”
Another Tubulis pipeline candidate, TUB-030, is a 5T4-targeting ADC that according to the companies has shown promising initial clinical data across various solid tumor types. TUB-030 is currently under study in the Phase I/IIa 5-STAR 1-01 trial (NCT06657222), a first-in-human study which aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-030 as a monotherapy in patients with advanced solid tumors. Tubulis has said it is developing TUB-030 for up to 13 undisclosed solid tumor indications.
Partners since 2024
The acquisition deal follows a two-year, up-to-$465 million collaboration with Tubulis launched in December 2024. Gilead gained access to Tubulis’ Tubutecan and Alco5 platforms after signing an exclusive option and license agreement to discover and develop an ADC against a solid tumor target.
At the time, Gilead agreed to pay Tubulis $20 million upfront, received an option that if exercised would have given Tubulis an additional $30 million—plus up to $415 million in payments tied to achieving development and commercialization milestones, as well as mid-single to low double-digit tiered royalties on sales of marketed products resulting from the collaboration.
“Today’s agreement follows a two-year collaboration with Tubulis, which has given us strong conviction in their programs and research capabilities,” Gilead Chairman and CEO Daniel O’Day said in a statement. “The agreement to acquire Tubulis is a significant milestone in Gilead’s progress in oncology. The company brings a clinical-stage candidate that is a potential new treatment for ovarian cancer, as well as a next-generation ADC platform and a promising early pipeline.”
“Bringing this potential into Gilead would further expand what is already the strongest and most diverse pipeline in our company’s history,” O’Day declared.
Investors appeared less enthusiastic about the acquisition, as shares of Gilead dipped 1.7% in early Tuesday trading to $137.80 as of 12:01 p.m. ET.
Tubulis is Gilead’s third announced acquisition this year. The biotech giant announced plans in March to buy Ouro Medicines for up to $2.18 billion, and in February agreed to acquire Arcellx for up to $7.8 billion—for which it agreed last week to extend its tender offer until 5 p.m. ET on April 24.
Under the acquisition deal, Gilead agreed to acquire all of the outstanding equity of Tubulis for $3.15 billion in upfront cash payable at closing, and up to $1.85 billion in payments tied to milestones.
The transaction is expected to close in the second quarter subject to expiration or termination of specified regulatory filings and other customary conditions.
Upon closing of the deal, Tubulis will operate as a dedicated ADC research organization within Gilead, with the Munich site serving as a hub for ADC innovation, building on its integrated discovery, manufacturing, and clinical capabilities to advance next generation ADCs.
Gilead said it plans to finance the transaction with a combination of cash on hand and senior unsecured notes. Gilead finished 2025 with $10.605 billion of cash, cash equivalents and marketable debt securities, up from $9.991 billion as of December 31, 2024.
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Good morning. Here in Chicago, cherry blossoms are blooming, rat birth control is working, and it finally feels like spring may be upon us.
Budget proposals aim to boost U.S. drugmaking
As part of President Trump’s 2027 budget blueprint, the FDA has proposed policies aimed at encouraging domestic development and manufacturing of drugs, such as making it easier for drugmakers to move into clinical testing in the U.S. and giving an “exclusivity” period to U.S.-based generics manufacturers.
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Today, a deep dive into why America’s most powerful health insurer is looking more and more like a technology company.
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The 2027 budget that the Trump administration released on Friday is in many ways a repeat of last year’s proposal: It includes deep cuts to the National Institutes of Health, the elimination of a health research agency, and the creation of a new agency devoted to chronic diseases called the Administration for a Healthy America.
Genomic testing for advanced cancer in the U.S. is hampered by unequal access across demographic groups and needs targeted policy solutions, researchers report.
Next-generation sequencing (NGS) was not carried out for the five most prevalent types of solid tumor among thousands of patients studied, the team revealed in JAMA Network Open.
And among those who did undergo this testing, wait time significantly varied according to race, insurance status, and practice setting.
“Our findings highlight the underrepresentation of certain patient demographics in tumor genomic profiling, revealing disparities in access to standard-of-care diagnostic modalities,” reported researcher Chadi Hage Chehade, MD, from the University of Utah, and coworkers.
“These results emphasize the need for healthcare policies to mitigate these gaps.”
Precision oncology has defined a new era in cancer treatment, enabling clinicians to tailor care based on the specific clinicogenomic features of a patient’s tumor, enabling more effective and less toxic treatment strategies.
NGS has emerged as a transformative technology, enabling comprehensive genomic profiling and uncovering alterations for targeted therapies.
To examine equity of care in the field, the researchers studied electronic health record data for patients with common advanced or metastatic cancers that spanned over 800 U.S. community and academic sites across the U.S. between 2018 and 2022.
The team examined time to first NGS testing and frequency of testing for 63,294 patients, including those with metastatic breast (19.1%), prostate (6.9%), pancreatic (9.7%), colorectal (21.6%), and non–small cell lung cancer (42.7%, NSCLC).
The median age in the group was 68 years and 53.7% was female. In terms of ethnicity, 2.7% were Asian, 10.0% were Black, 6.0% were Hispanic, 61.0% were White, and 20.3% were other races and ethnicities.
The frequency of testing increased over the four-year span across all cancer types, but by the final year of study up to 40% to 50% of patients were still not receiving NGS testing.
Results showed there were differential rates of testing and longer waiting times to NGS testing in some groups.
Patients with lower socioeconomic status (SES), non-Hispanic Black or Hispanic patients, those covered by Medicare, Medicaid, or other government programs, and those treated at an academic practice setting were significantly less likely to be tested in some of cancers than patients with high SES, who were non-Hispanic White, those covered by a commercial health plan, or those treated in community practice, respectively.
Among specific cancers, Hispanic patients were significantly less likely to be tested in metastatic breast or prostate cancer, and non-Hispanic Black patients were less likely to receive NGS in advanced NSCLC, metastatic colorectal or metastatic pancreatic cancer.
The findings highlight the need to improve access to standard-of-care diagnostic modalities and serve as a call to improve NGS testing rates nationwide, said Igor Makhlin, MD, in an accompanying Commentary article.
“While the accelerating pace of research and AI-driven technology is poised to herald the next generation of discoveries that translate into greater survival for patients with cancer, we cannot ignore the increased burden to stay up to date, largely born by community oncologists who manage a wide gamut of solid and liquid cancers,” he maintained.
“Creation and adoption of innovative strategies to support clinicians in implementing breakthrough advances into their practice regardless of zip code, practice site, or other factors will require a concerted effort by all relevant stakeholders, but closing this gap in GCC is absolutely necessary. Our patients are depending on us.”
<![CDATA[Early MRS data show AL001 delivers lithium effects across the brain while sparing glutamate, hinting at better tolerability than lithium carbonate.]]>
For some advanced cancers, sequencing the tumor genome should be one of the first steps patients and physicians take. But a new study finds that many patients never receive genomic testing and so never get the chance to know if they might have benefitted from newer, more targeted therapies.
The study, published on Tuesday in JAMA Network Open, examined how many patients diagnosed with one of five different metastatic cancers received genetic sequencing for the cancers. For most cancers in the study, roughly half of patients in the cohort received genetic sequencing. Patients with low income, Medicare or Medicaid coverage, and Black or Hispanic race or ethnicity were also less likely to receive sequencing.
Cancer medicine and research have made enormous progress over the last few decades. The overall five-year survival rate has pushed up to 70% as of 2026, and the five-year survival rate for metastatic cancer has doubled since the 1960s. That’s in large part thanks to advances in medicines and technologies that can help treat cancer, like targeted therapies that work by exploiting key cancer mutations.
MIT Technology Review Explains: Let our writers untangle the complex, messy world of technology to help you understand what’s coming next. You can read more from the series here.
As the conflict in Iran has escalated, a crucial resource is under fire: the desalination technology that supplies water across much of the region.
In early March, Iran’s foreign minister accused the US of attacking a desalination plant on Qeshm Island in the Strait of Hormuz and disrupting the water supply to nearly 30 villages. (The US denied responsibility.) In the weeks since, both Bahrain and Kuwait have reported damage to desalination plants and blamed Iran, though Iran also denied responsibility.
In late March, President Donald Trump threatened the destruction of “possibly all desalinization plants” in Iran if the Strait of Hormuz was not reopened. Since then, he’s escalated his threats against Iran, warning of plans to attack other crucial civilian infrastructure like power plants and bridges.
Countries in the Middle East, particularly the Gulf states, rely on the technology to turn salt water into fresh water for farming, industry, and—crucially—drinking. The mounting attacks and threats to date highlight just how vital the industry is to the region—a situation made even more precarious by rising temperatures and extreme weather driven by climate change.
Right now, 83% of the Middle East is under extremely high water stress, says Liz Saccoccia, a water security associate at the World Resources Institute. Future projections suggest that’s going to increase to about 100% by 2050, she adds: “This is a continuing trend, and it’s getting worse, not better.”
Here’s a look at desalination technology in the Middle East and what wartime threats to the critical infrastructure could mean for people in the region.
A vital resource
Desalination technology has helped provide water supplies in the Middle East since the early 20th century and became widespread in the 1960s and 1970s.
There are two major categories of desalination plants. Thermal plants use heat to evaporate water, leaving salt and other impurities behind. The vapor can then be condensed into usable fresh water. The alternative is membrane-based technology like reverse osmosis, which pushes water through membranes that have tiny pores—so small that salt can’t get through.
Early desalination plants in the Middle East were the first type, burning fossil fuels to evaporate water, leaving the salt behind. This technique is incredibly energy-intensive, and over time, processes that rely on filters became the dominant choice.
Membrane technologies have made up essentially all new desalination capacity in recent years; the last major thermal plant built in the Gulf came online in 2018. Many reverse osmosis plants still rely on fossil fuels, but they’re more efficient. Since then, membrane technologies have added more than 15 million cubic meters of daily capacity—enough to supply water to millions of people.
Capacity has expanded quickly in recent years; between 2006 and 2024, countries across the Middle East collectively spent over $50 billion building and upgrading desalination facilities, and nearly that much operating them.
Today, there are nearly 5,000 desalination plants operational across the Middle East.
And looking ahead, growth is continuing. Between 2024 and 2028, daily capacity is expected to grow from about 29 million cubic meters to 41 million cubic meters.
Uneven vulnerabilities
Some countries rely on the technology more than others. Iran, for example, uses desalination for about 3% of its municipal fresh water. The country has access to groundwater and some surface water, including rivers, though these resources are being stretched thin by agriculture and extreme drought.
Other nations in the region, particularly the Gulf countries (Bahrain, Qatar, Kuwait, the United Arab Emirates, Saudi Arabia, and Oman), have much more limited water resources and rely heavily on desalination. Across these six nations, all but the UAE get more than half their drinking water from desalination, and for Bahrain, Qatar, and Kuwait the figure is more than 90%.
“The Gulf countries are much, much more vulnerable to attacks on their desalination plants than Iran is,” says David Michel, a senior associate in the global food and water security program at the Center for Strategic and International Studies.
There are thousands of desalination facilities across the region, so the system wouldn’t collapse if a small number were taken offline, Michel says. However, in recent years there’s been a trend toward larger, more centralized plants.
The average desalination plant is about 10 times larger than it was 15 years ago, according to data from the International Energy Agency. The largest desalination plants today can produce 1 million cubic meters of water daily, enough for hundreds of thousands of people. Taking one or more of these massive facilities offline could have a significant effect on the system, Michel says.
Escalating threats
Desalination facilities are quite linear, meaning there are multiple steps and pieces of equipment that work in sequence—and the failure of a component in that chain can take an entire facility down. Attacks on water inlets, transportation networks, and power supplies can also disrupt the system, Michel says.
During the Gulf War in 1991, Iraqi forces pumped oil into the gulf, contaminating the water and shutting down desalination plants in Kuwait.
The facilities are also generally located close to other targets in this conflict. Desalination is incredibly energy intensive, so about three-quarters of facilities in the region are next to power plants. Trump has repeatedly threatened power plants in Iran. In response, Iran’s military has said that if civilian targets are hit, the country will respond with strikes that are “much more devastating and widespread.” Other governments and organizations, including the United Nations, the European Union, and the Red Cross, have broadly condemned threats to infrastructure as illegal.
But war isn’t the only danger facing these plants, even if it is the most immediate. Some studies have suggested that global warming could strengthen cyclones in the region, and these extreme weather events could force shutdowns or damage equipment.
Water pollution could also cause shutdowns. Oil spills, whether accidental or intentional, as in the case of the Gulf War, can wreak havoc. And in 2009, a red algae bloom closed desalination plants in Oman and the United Arab Emirates for weeks. The algae fouled membranes and blocked the plants from being able to take water in from the Persian Gulf and the Gulf of Oman.
Desalination facilities could become more resilient to threats in the future, and they may need to as their importance continues to grow.
There’s increasing interest in running desalination facilities at least partially on solar power, which could help reduce dependence on the oil that powers most facilities today. The Hassyan seawater desalination project in the UAE, currently under construction, would be the largest reverse osmosis plant in the world to operate solely with renewable energy.
Another way to increase resilience is for countries to build up more strategic water storage to meet demand. Qatar recently issued new policies that aim to improve management and storage of desalinated water, for example. Countries could also work together to invest in shared infrastructure and policies that help strengthen the water supply through the region.
Preparedness, resilience, and cooperation will be key for the Middle East broadly as critical infrastructure, including the water supply, is increasingly under threat.
“The longer the conflict goes on, the more likely we’ll see significant water infrastructure damage,” says Ginger Matchett, an assistant director at the Atlantic Council. “What worries me is that after this war ends, some of the lessons will show how water can be weaponized more strategically than previously imagined.”
A new study published in Nature Chemical Biology titled, “Munc13-4–STX7 inhibitors impair endosomal TLR activation and systemic inflammation,” scientists from Scripps Research have developed a new class of drug compounds, called ENDOtollins, that reduce harmful inflammation while maintaining the body’s ability to fight infections. The results offer new directions to treat autoimmune diseases, such as lupus, and rheumatoid and juvenile arthritis, which together affect more than 15 million Americans.
“A key component of our approach is to begin by understanding the biological mechanisms at play,” said Sergio Catz, PhD, professor at Scripps Research and corresponding author of the study. “By accomplishing this first, we can more easily target the pathway driving inflammation without affecting other important processes.”
Current autoimmune disease treatments, such as hydroxychloroquine, function by broadly blocking endosomes. While effective, this approach can lead to significant side effects, including gastrointestinal problems and, less commonly, vision damage, that cause patients to stop treatment.
The authors focused on two proteins, Munc13-4 and syntaxin 7, that bind together to activate Toll-like receptors (TLRs), immune sensors that activate endosomes. This mechanism plays a key role in detecting foreign DNA and RNA from viruses and bacteria. In autoimmune diseases, TLRs become overactive and trigger chronic, damaging inflammation in the absence of a threat.
The team screened roughly 32,000 compounds and identified molecules that specifically block the Munc13-4–syntaxin 7 interaction without disrupting other cellular functions. Given that Munc13-4 is found mainly in immune cells, the compounds offer a targeted approach to reduce inflammation.
“Most treatments for autoimmune diseases manage symptoms; they don’t change the underlying course of the disease,” said Hugh Rosen, MD, PhD, professor at Scripps Research and co-author of the study. “What’s exciting about this approach is its potential to be disease-modifying: targeting the specific molecular machinery that drives inflammation, rather than broadly suppressing the immune system.”
Notably, the study screened compounds in an intact cellular environment which contrasts from many drug screening approaches, which extract proteins from the cell.
“By maintaining the proteins in their natural environment, we increase the likelihood that compounds we find will actually work in living cells,” said Jennifer Johnson, PhD, first author and senior staff scientist at Scripps Research.
The most potent compound, ENDO12, reduced inflammation in animal models that were also given a TLR-activating molecule. Blood levels of inflammatory markers, including immune system activators IL-6 and IFN-γ, and the enzyme myeloperoxidase, dropped significantly in animals that were treated.
ENDO12 treated animals demonstrated normal antiviral immune response when exposed to a virus. This selectivity addresses the concern that dampening inflammation with immunosuppressive drugs may leave patients vulnerable to infections.
Looking ahead, the team will test ENDOtollins in models that more closely mimic human autoimmune diseases and evaluate the compounds’ chemistry for potential clinical use.
Beyond autoimmune conditions, the researchers suggest ENDOtollins might help treat cytokine storms, the dangerous immune overreactions seen in patients with severe COVID-19 and as a side effect of CAR T cancer therapy. Both involve excessive IL-6 and runaway inflammation.
While translating these findings into treatments for patients remains a long-term goal, Catz emphasizes that the mechanistic insights are valuable in their own right. ENDOtollins can serve as precision tools to probe other cellular processes regulated by endosomes and lysosomes, including pathways implicated in neurodegeneration and immune dysfunction.
A woman lies on an exam table, holding her partner’s hand tightly with anticipation, as a technician glides an ultrasound probe across her abdomen. On the screen, shifting staticky shadows resolve into a skull, a liver, and the flicker of a beating heart. For many families, this moment brings joy and relief. For others, it’s paralyzing, as doctors detect signs that something is wrong.
A single nucleotide change can cause neurodevelopmental delays and dimorphism, failing livers, and arrhythmia-ridden hearts. For decades, medicine could only identify these conditions, usually after birth. Prenatal screening has made it easier to detect progressive diseases like Duchenne muscular dystrophy, which degenerates and damages muscles before symptoms typically appear in childhood. But treating before birth could preserve tissue prior to the onset of irreversible deterioration.
Once unthinkable, genetic diseases can now be treated before birth. Fetal genetic intervention—including early screening, in utero gene therapy, stem cell transplantation, and even embryo editing—aims not just to diagnose disease but to correct it at its earliest stages. It is a rapidly advancing frontier, defined by technological promise and profound ethical questions.
It starts with detection
Jennifer Hoskovec, vice president of medical affairs at BillionToOne, has spent more than 20 years in prenatal genetics, an era dominated by risk assessment rather than intervention.
Historically, prenatal genetic screening has fallen into two main categories. Aneuploidy testing determines the risk of Down syndrome and other trisomies, sex chromosome abnormalities, and specific microdeletions. Screening is essential for these de novo mutations, which have no U.S. Food and Drug Administration (FDA)-approved genetic interventions. High-risk Down syndrome patients may receive a fetal echocardiogram, closer ultrasound monitoring, or tertiary care delivery with neonatal support. The standard practice is to screen, monitor, and manage.
Jennifer Hoskovec Vice President BillionToOne
The second category involves inherited recessive conditions like cystic fibrosis (CF), spinal muscular atrophy (SMA), and phenylketonuria. If both parents are carriers for the same genetic mutation, then their child has a 25% chance of being affected. Testing typically requires samples from both parents. If both are carriers, chorionic villus sampling (CVS) and amniocentesis can detect fetal abnormalities in the first and second trimesters, respectively. However, getting each partner to follow up is a major hindrance. “When people go through a screening process and are found to be carriers, less than 50% of their partners complete the testing,” Hoskovec told Inside Precision Medicine. “Half of U.S. carriers of these genetic conditions, whether common or rare, don’t know what it means for their pregnancy. That limits their ability to get diagnostic testing because we do not have all the pieces of the puzzle.”
Hoskovec’s team developed a workaround: a single-gene noninvasive prenatal test that analyzes fetal cell-free DNA (cfDNA) circulating in maternal blood. Around nine weeks into pregnancy, fragments of fetal DNA shed from the placenta can be sequenced and quantified. If a mother is a carrier for a condition like CF or sickle cell disease, the test looks for a second variant that is not present in her DNA and forms evidence of paternal contribution.
“For example, if a mother has [the] sickle cell trait, we first sequence the full beta-globin gene in the cfDNA, which contains a mixture of maternal and fetal DNA,” Hoskovec said. “We look for a second variant not present in the mother that would indicate paternal contribution.”
Despite not replacing CVS or amniocentesis, Hoskovec said the result is highly sensitive, identifying 95% of affected pregnancies in the conditions it covers. Crucially, it does not require partner testing. “This is a stepping stone,” Hoskovec explained. “This earlier detection will likely accelerate the field by increasing the number of eligible patients for clinical studies and registries, improving equitable access across ethnic groups, and advancing precision medicine in prenatal care.”
Avoiding germline editing
David H. Stitelman, MDr Associate Professor Yale-New Haven Children’s Hospital and Yale School of Medicine
As screening opens the door, fetal surgeons and gene therapy researchers are taking their first steps through it. A pediatric surgeon at the Yale School of Medicine, David H. Stitelman, MD, believes prenatal treatment has benefits. The fetus is small, so it can receive higher doses based on weight. As its immune system is still developing and more tolerant, stem cells are growing quickly and organs are still being formed, so problems can be fixed before they become permanent. Because the placenta exchanges oxygen, lung conditions like congenital diaphragmatic hernia can be treated during fetal life. But once a newborn takes a first breath, defective lungs can spell immediate crisis.
Fetal therapy is not new. Specialized centers have performed open fetal surgery for spina bifida and diaphragmatic hernia lung growth, and blood transfusions for fetal anemia dating back to the 1960s. What is new is the molecular toolkit. Stitelman’s lab is investigating gene editing methods that use the cell’s repair machinery to fix one- to three-base-pair DNA errors. Another team, led by pediatric and fetal surgeon Tippi MacKenzie, MD, at the University of California, San Francisco, is using viruses to replace genes for lysosomal storage diseases and fetal stem cells for alpha thalassemia.
Some diseases require only modest correction. In hemophilia, one percent normal clotting factor expression improves outcomes greatly. Increasing the expression of functional CFTR protein to 15% of wild-type levels may cure CF or at least make it manageable. Even a small number of liver cells corrected in hereditary tyrosinemia can boost growth and repopulate the organ. However, some situations, such as congenital cancer syndromes, may require nearly 100% correction. At present, Stitelman’s team achieves single-digit percentage editing in models of CF and beta thalassemia. “We’re in the optimization phase,” Stitelman told Inside Precision Medicine. “We are testing different nanoparticles and generations of editing strategies to incrementally reach therapeutic levels.”
Stitelman draws a clear ethical boundary: this is somatic editing, not germline editing. The aim is to treat the fetus as a patient, not to create heritable genetic changes. Instead of editing embryos in vitro, systemic therapeutic agents are delivered to avoid reproductive cell damage.
Unintended germline modification remains a concern. Editing a target gene could inadvertently disrupt developmental genes and affect future generations. But, Stitelman argues, medicine always carries risk. “In 1950, children with leukemia all died,” said Stitelman. “Today, some forms have a 98% long-term survival rate with chemotherapy. We know chemotherapy can cause germline mutations, yet we accept that risk because it saves lives. With gene editing, the issue is not zero risk but understanding and quantifying the risk. Ideally, there would be no measurable off-target effects. In the places we have examined, we have not seen off-target effects.”
One pregnancy, two patients
In a landmark trial in 2011 known as the Management of Myelomeningocele Study, investigators found that fetal surgery for severe spina bifida (myelomeningocele) achieved better results than postnatal repair. Surgically closing the spinal defect in utero improved motor function and reduced the need for shunting to relieve hydrocephalus. The benefit was so clear that the trial was stopped early and influenced how doctors treat structural birth defects.
Aijun Wang, PhD Professor University of California, Davis
At the University of California, Davis, biomedical engineer Aijun Wang, PhD, is working closely with fetal surgery pioneer Diana L. Farmer, MD, to evolve fetal intervention from heroic surgery to cellular and molecular therapy. Wang and Farmer launched the Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe) trial, combining fetal surgery with stem cell transplantation. The goal is to not only close the spinal defect but also restore neural tissue and improve long-term function.
The lens that Wang has used to focus his research is fetal and maternal safety. “The fetus is the patient, but treatment inevitably carries some risk to the mother,” Wang told Inside Precision Medicine. “Open fetal surgery, in particular, poses significant maternal risk. Genetic treatments introduce additional uncertainties because the long-term effects of DNA modification are not fully understood. Safety must remain the highest priority.”
Genetic medicine delivery is a critical challenge for all life stages, but the stakes are particularly high for a developing fetus. In fetal development, targeting stem cell populations is especially important because these cells are highly active, proliferating, and migrating. If edited successfully at the right developmental window, their progeny will carry the correction. The problem would be if the edit was not just unsuccessful but detrimental.
Wang’s lab focuses on delivery systems, particularly lipid nanoparticles carrying mRNA-encoding gene-editing enzymes. For genetic manipulation and high-throughput screening, Wang’s lab utilizes mouse models. Fetal sheep are used for scaling and dosing, while human organoids are used for human-specific editing and functional outcomes.
“In our clinical work, we have engaged with the FDA and conducted extensive preclinical studies,” said Wang. “Using multiple complementary models is essential. Combining small animal models, large animal translational models, and human organoid systems provides a comprehensive framework for product development, from early screening to human-focused therapeutic design.”
Although the field is highly exciting and progressing rapidly, Wang warns against premature application, which could be dangerous. Safety, developmental biology, ethical considerations, and multidisciplinary collaboration are all essential. “Despite the excitement in the field, we must proceed cautiously,” said Wang. “There is strong potential for correcting specific mutations, especially point mutations, using precise gene editing approaches such as base editing. However, safety evaluation must precede rapid clinical application.”
Effective progress requires a village of physicians, surgeons, researchers, engineers, and ethicists working together. Scientific progress requires caution, responsibility, and thorough evaluation before clinical use.
The earlier, the better
If fetal intervention treats a diagnosed fetus, embryo editing operates even earlier—at the blastocyst stage in in vitro fertilization (IVF). Norbert Gleicher, MD, a fertility specialist known for treating some of the oldest and most difficult IVF patients in the United States, approaches genetic technologies with caution. Due to biological mosaicism, sampling limitations, and his belief that many abnormal embryos self-correct or develop normally, Gleicher opposes preimplantation genetic testing for aneuploidy.
Norbert Gleicher, MD Founder & Medical Director Center for Human Reproduction
But when it comes to single-gene diseases, he sees a different calculus. Couples with recessive mutations may have one-in-four embryos affected, and in dominant or X-linked diseases, half may carry the mutation. For patients who produce few embryos—especially older women—discarding affected embryos can mean losing precious chances at pregnancy. “If you can cure an embryo rather than discard it,” Gleicher told Inside Precision Medicine, “that makes a lot of sense.”
For single-gene diseases, Gleicher believes genetic editing with CRISPR or other platforms is the most straightforward intervention. He points to the 2025 work at the Children’s Hospital of Philadelphia on Baby KJ as a recent milestone. Even partial correction, which Gleicher believes is likely the case with Baby KJ—though no liver biopsies have been extracted—can transform prognosis. Gleicher said, “Correcting some cells was enough to clinically cure the baby, at least for the time being, from symptoms of a disease that historically kills affected children within a few years. However, we do not know whether the treated baby, who likely still has many affected cells, might become symptomatic again later in life.”
To Gleicher, success in a newborn is all the more reason to apply genetic intervention to fetal stages. “If this can be successful in a full human being, imagine how much easier it would be at the blastocyst stage, or even earlier at the cleavage stage, when the embryo consists of only six to eight cells,” said Gleicher. “If [CRISPR] is applied at that point, correcting those six to eight cells would mean that all their daughter cells would also be corrected. The result would be a normal baby at birth. That is the much stronger argument in this case.”
Just because something is possible, it doesn’t necessarily mean it should be done, and Gleicher establishes a clear ethical boundary. Editing to prevent a devastating single-gene disease is one thing. Editing for traits—eye color, intelligence, polygenic risk scores—is another. Polygenic predictions explain only a fraction of trait variance, and embryo implantation itself is uncertain. To him, offering polygenic selection in IVF is not only scientifically dubious but also ethically troubling. “It is surprising that professionals, particularly in genetics, would suggest such an approach,” said Gleicher. “It is worse than snake oil, because while snake oil may occasionally work by accident, this carries a real risk of causing serious harm.”
A pretty penny
What ultimately restricts fetal genetic intervention is timing. Early screening increases experimental trial eligibility, and early treatment may preserve organ development before irreversible damage. In conditions like CF and SMA, where postnatal gene therapies are expensive and delivered after injury, fetal intervention could change outcomes. Frontline screening can identify high-risk pregnancies at 11 weeks without family history or ethnicity, expanding trial access.
Yet, fetal genetic interventions require specialized teams, advanced delivery systems, counseling, and long-term follow-up. Without careful planning and reimbursement policies, only a few top-tier centers could progress, widening the gap. Ethical scrutiny remains inseparable from progress. Innovation must balance maternal risk, fetal benefit, and future consequences with safety, appropriate use, and clear limits. As prenatal care shifts from prediction to prevention, restraint and evidence will determine its future.
Jonathan D. Grinstein, PhD, North American editor for Inside Precision Medicine, investigates the most recent research and developments in a wide range of human healthcare topics and emerging trends, such as next-generation diagnostics, cell and gene therapy, and AI/ML for drug discovery. He is also the host of the Behind the Breakthroughs podcast, featuring people shaping the future of medicine. Jonathan earned his PhD in biomedical science from the University of California, San Diego, and a BA in neural science from New York University.
