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Researchers at the University of Essex have developed microscopic medicines that could pave the way for new approaches to treating neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and motor neurone disease (MND).
Working with an international team, the scientists used artificial intelligence to create extremely small antibody fragments that can be produced directly inside human cells. Once there, the fragments can attach to proteins associated with disease.
Ordinary antibodies generally function outside cells. The newly redesigned fragments, called intrabodies, have instead been engineered to remain stable within cells, allowing them to target proteins involved in neurodegenerative conditions.
Electrical Charge Helps Antibodies Survive Inside Cells
The research was funded by the MND Association and led by Dr. Caitlin O’Shea and Dr. Gareth Wright from the School of Life Sciences. The team discovered that electrical charge is a key factor in determining whether antibody fragments can remain stable and functional inside cells.
Using that insight together with AI-powered protein redesign, the researchers converted 672 different antibodies into intrabodies capable of targeting important disease-related proteins.
The advance could give scientists new ways to study and potentially treat neurodegenerative diseases by acting directly inside living cells, where many of the biological processes involved in these conditions begin.

Following publication of the research in Nature Communications, the redesigned molecules will be made freely available to other scientists.
Lead author Dr. O’Shea, who specializes in MND and Parkinson’s disease, said: “We looked at the properties of millions of antibodies and compared them with human proteins found inside the cell.
“From this we figured out that antibodies usually have the wrong charge to exist inside cells without sticking together.
“We used software developed by Nobel Prize winner David Baker and his group to redesign our antibody fragments, so they had the right charge and are super stable.”
Repurposing Millions of Existing Antibodies
The researchers believe the findings could allow scientists to find new uses for millions of antibodies developed during decades of biomedical research.

Rather than starting entirely from scratch, existing antibodies may be adaptable for use as powerful laboratory tools and, potentially, as the foundation for future treatments aimed at disease-causing proteins.
Dr. Wright, who directed the research, said the approach could have major implications for diseases that affect tens of millions of people around the world.
“We’ve made intracellular antibodies that stick to proteins that cause neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and motor neurone disease,” said Dr. Wright.
“These diseases can lead to cognitive impairment, forgetfulness, loss of muscle control and death. They affect over one million people in the UK alone, so they are a big public health concern.
“There are no cures for these diseases and finding molecules that interact with the proteins that cause them in their native environment is a major challenge in the medicine discovery process.”
New Therapeutic Possibilities for MND and Other Diseases
The MND Association welcomed the findings and highlighted their potential importance for future treatments.
Chief Scientist at the charity, Dr. Brian Dickie, said: “Dr. Wright and his colleagues have made a significant advance in overcoming one of the key challenges that has impeded the development of antibodies as treatments for neurodegenerative diseases, such as MND.
“Their research findings provide optimism that a combination of this novel ‘intrabody’ science with emerging gene therapy techniques may lead to new therapeutic strategies that can hit specific molecular targets within neurones.”

‘I can’t do the things my friends do’: Life as a teenage carerImage source, OtherByNick TriggleHealth correspondentPublished20 August 2026Ava-Grace Britton is 17 and studying acting at college in north London. She likes going out, seeing her friends and wants to go to university next year.Unlike most of her peers, however, she also cares for her father, Paul, who has significant mobility and memory issues after suffering a series of strokes eight years ago.Along with her mother Karen, Ava-Grace monitors Paul’s blood glucose levels, gives him medication and helps with dinner and jobs around the house. “I worry about him all the time,” Ava-Grace told the BBC. “Before I go to college I help him and most days I have to return home quickly to look after him.”She is not alone. Officially, census data suggests there are around 130,000 carers under the age of 18 in England and Wales.But the true figure is thought to be much higher, with many young carers hidden from view. The Carers Trust estimates there could be as many as 1 million carers under 18, with another 500,000 aged 18 to 25.For some the responsibilities are significant, amounting to more than 50 hours a week – with consequences on young carers’ social and academic prospects. ‘Life upside down’Paul’s strokes were brought on by a sepsis infection, which he caught after cutting his thumb at work. His health is further compromised by diabetes which needs careful monitoring.His condition deteriorated so much he had to give up work as a borehole engineer. He is now cared for full-time by Ava-Grace and Karen, who runs her own charity which organises lunch clubs for the elderly and vulnerable.”It turned our life upside down,” said Karen.”Paul spent three months in hospital and in rehab. I don’t know how I would cope without Ava-Grace.”Ava-Grace says her caring responsibilities have demanded a number of trade-offs over the years.”You have to make sacrifices. I can’t do all the things my friends do,” she said. “At one point I was really enjoying dance and could have started competing, but it would have been a huge time commitment which wasn’t possible.While enjoying college now, she had to move schools several times after being bullied and struggling with attendance because of her caring responsibilities and epilepsy, which she has to manage.”I worry about the future,” she said. “I really want to go to university, but can’t imagine going anywhere too far from home. I know my dad needs me.”Image source, OtherMore than half of young carers, like Ava-Grace, provide support to parents.The rest mainly look after siblings and grandparents. The Carers Trust says there has been a big rise in non-parent carers in recent years as the cost of living crisis has meant parents have had to prioritise earning money, leaving children to care for other family members.That can make socialising and pursuing hobbies difficult as well as lead to higher rates of bullying, school absence and even suspensions.Young carers are 25% less likely to achieve five GCSE passes including English and Maths than their peers, according to Department for Education data.As a result they are twice as likely to be out of education, employment or training for two years or more.Support for carersSome support is available. Young carers are entitled to assessments from their local council to look at the impact on their health, education and wellbeing.”When young carers get these it can make a real difference,” said Andy McGowan, the lead on young carers at the Carers Trust. “But it takes many years of caring before they are actually identified. And then the support in place to help is patchy, it really depends on where you live.”McGowan, who was a young carer himself to both his parents, says even when help is given to the young in the form of respite breaks, peer support and counselling, the underlying issue – the caring demands being placed on them – is often not addressed.”The threshold to get adult social care from councils to relieve the caring burden is so high, many don’t get help. Until that is addressed, the inequalities young carers face will not be tackled.”The NHS could do more, he added, particularly in terms of preventative and early support for things like substance misuse and mental health, which are also contributory factors to the caring responsibilities young carers have.”Often young carers are left to fight their own battles for too long – and so school and their own health come second,” he said. In July, the government published an action plan for unpaid carers which included measures to support young carers, including improved help in schools and joined-up support between the NHS, social care and education. Other parts of the UK have their own policies – in Scotland, for example, there is a dedicated young carers’ grant.”Through our new national care service, this government is determined to build a system that recognises the extraordinary contribution of unpaid carers, supports them better and, in particular, helps young carers,” a government spokesman told the BBC.For families like the Brittons, more help cannot come soon enough. “I worry about the impact caring has on Ava-Grace,” said Karen. “She has had to grow up very quickly – that has had benefits, she is calmer and more mature than many girls her age and she has a real strength about her. But Ava-Grace and others like her need more help and understanding.”Get in touchHave you spent time as a young carer? 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Weekly type 2 diabetes jab could replace daily injectionsImage source, Getty ImagesByDominic HughesHealth correspondentPublished20 August 2026Hundreds of thousands of people with type 2 diabetes could get access to a new weekly insulin jab to replace daily injections, reducing the number needed each year by 86%.Patients still have to wait for the treatment to be approved by the medicines regulator before it is made available on the NHS. The treatment, known as Onswik and made by Eli Lilly, is said to work as well as daily insulin jabs but only needs to be injected once a week.The charity Diabetes UK says it will help people manage their condition better, especially those who have extra care needs and who require help to inject every day.Around 4.7 million people in the UK were living with diabetes in 2024-25, of which roughly 90% had type 2. The condition means the body can’t make enough of a hormone called insulin, or the insulin it makes doesn’t work properly – also known as insulin resistance.Diabetes UK says that around 1 in 4 people with type 2 diabetes takes insulin.Greater flexibility Moving from daily injections to a weekly jab is most likely to benefit those who need help with their injections.That might include frailer people and those with sight loss, limited hand movement and learning disabilities.People who have difficulty following the steps involved in a daily injection or those who struggle to stick to their treatment regime are also likely to be helped by the new drug.Douglas Twenefour, head of clinical at Diabetes UK, said: “For some, especially those with additional care needs, moving from daily insulin injections to a once-weekly option could help manage their diabetes more easily, improving their quality of life.”It’s essential that everyone who could benefit is supported by their healthcare team to make informed decisions, and that this treatment helps reduce inequities in diabetes care.”Helen Knight, director of medicines evaluation at Nice, said the new treatment could make a “real difference to the day-to-day lives of people with type 2 diabetes, especially those who rely on a carer, family member or healthcare professional to help them inject”. She added: “This recommendation is the result of rigorous, evidence-based decision making, striking a balance between the benefits to patients and the best use of limited NHS funding.”The initial approval for the new treatment has come from the National Institute for Health and Care Excellence (Nice), which is the body responsible for deciding what medication and treatments should be available on the NHS.But before type 2 diabetes patients can access the treatment via the NHS it needs to be licensed by another body, the medicines regulator, the Medicines and Healthcare products Regulatory Agency (MHRA).Health officials say they are waiting on the MHRA’s ruling on the treatment “to understand whether it could be rolled out on the NHS”.Nice guidance applies to the NHS in England, but the NHS in Wales also frequently follows its recommendations.They aren’t automatically followed in Northern Ireland where they are reviewed by the Department of Health, and in Scotland the process is managed by the Scottish Medicines Consortium.More on this storyMore young women in their 20s are getting type 2 diabetesPublished22 JulyMore weight-loss drugs could be offered as part of new diabetes carePublished20 August 2025

Vapes could lead to health harms in children, doctors warnImage source, Getty ImagesByHugh Pym, Health editor 

A mother’s age can influence the physical traits and behavior of her offspring in humans and across many other animal species. Researchers refer to these changes as maternal age effects. Although the phenomenon is common throughout the animal kingdom, scientists are still working to understand the biological processes underlying it and why it has persisted over evolutionary history.
“Maternal age effects are incredibly common, from invertebrates up through humans, elephants, other primates and other mammals,” said Kristin Gribble, an associate scientist in the Bay Paul Center at the Marine Biological Laboratory. “Nearly all forms of life show some level of maternal age effect, and most are negative effects caused by advanced maternal age.”
Rotifers Offer Clues to Maternal Age Effects
To investigate how information about maternal age is passed to offspring, Gribble’s laboratory studies rotifers, tiny aquatic animals that reproduce rapidly and are well suited for laboratory experiments.
“Understanding the mechanism in these simple invertebrates can help us understand how maternal age effects occur in people as well,” she said.
Research on rotifers has led the team to an unexpected possibility. Maternal age effects may be controlled by epigenetic processes that change how genes are used rather than by mutations that alter the underlying DNA sequence.
Work in Gribble’s lab by postdoctoral scientist Alyssa Liguori, who is now an assistant professor at SUNY-New Paltz, examined two different genotypes from the same rotifer species. The results showed that the effects associated with maternal age did not become progressively stronger with each generation. Instead, those effects could be reversed within a single generation.

That rapid reversal argues against the idea that maternal age effects are primarily caused by the gradual buildup of cellular damage or DNA mutations associated with aging, as many researchers had previously suspected. The findings instead point toward an epigenetic process involving histone modifications. These modifications can influence whether genes are switched on or off.
How Mothers May Pass Biological Information
Gribble’s team is now testing whether histone modifications are responsible for the maternal age effects observed in the rotifers. She is also considering whether mitochondrial DNA, which is generally inherited from the mother, could play a role “in transmitting information about maternal age from moms to offspring.”
Genetic differences may also determine how strongly offspring are affected by an older mother.
“There are likely gene variants out there that are protective of negative effects of advanced maternal age,” Gribble said. “In one of our strains, we saw that offspring from older mothers had a longer lifespan, implying a genetic mechanism may be involved in that beneficial effect.”
That finding highlights an important complication. Although advanced maternal age is often associated with harmful outcomes, genetic variation may sometimes reduce those effects or even produce benefits.

Why Maternal Age Effects Persist
A major evolutionary puzzle is why maternal age effects remain so widespread. Offspring born to older mothers often live shorter lives, reproduce less, and have lower evolutionary fitness. In theory, natural selection might be expected to gradually remove traits that produce such disadvantages. Yet maternal age effects continue to appear across an extraordinary range of species.
Gribble thinks part of the explanation may be that natural selection becomes weaker later in an organism’s life.
“Selective pressure is much lower at advanced ages, particularly in rotifers which are really geared to do most of their living and reproducing very young,” she said.
By the time female rotifers reach advanced ages, they have already produced most of their offspring. As a result, there may be less evolutionary pressure favoring traits that help older females produce especially fit offspring.
Biological Effects Across Generations
For Gribble, one of the most compelling questions is how biological information can travel beyond a single generation.
“I want to know how it happens that information about a grandmother or great-grandmother’s environment can affect the phenotype of her grandchild or great-grandchild,” she explains.
Understanding how maternal effects move across generations could eventually deepen scientists’ knowledge of human health and contribute to future approaches in precision medicine. The research suggests that an individual’s biology may reflect more than the DNA inherited at conception. Conditions experienced by previous generations could also matter.
“It’s not just about what’s in your genome as an individual,” Gribble said, because “your health potentially depends on the health and environment of your mom and grandmother and great-grandmother.”

Salmonella outbreak: What we know so far Image source, Getty ImagesBySmitha MundasdHealth reporter Published19 August 2026The UK Health Security Agency (UKHSA) has recently declared a national outbreak,

Coffee is consumed around the world every day, and earlier research has associated coffee drinking with a reduced risk of conditions including type 2 diabetes and cardiovascular disease. Scientists still do not fully understand the biological processes that might explain those connections. Now, new research from Finland suggests that regular coffee consumption is associated with healthier body composition, favorable metabolic markers, and distinct patterns involving sex hormones in men and women.
Researchers at the University of Oulu analyzed information from 2,264 people who were 46 years old and taking part in the Northern Finland Birth Cohort 1966. The team investigated how participants’ usual coffee intake related to circulating metabolites, indicators of cardiometabolic risk, and sex hormone levels.
Coffee Drinkers Had Less Fat and More Muscle
People who consumed more coffee tended to have lower levels of both total body fat and visceral fat, along with greater skeletal muscle mass. These differences appeared even though participants with higher and lower coffee intake had a similar body mass index (BMI).
Higher coffee consumption was also associated with lower circulating concentrations of branched-chain amino acids in both men and women. When chronically elevated, these biomarkers have previously been associated with insulin resistance and a greater risk of developing type 2 diabetes.
Coffee Intake Was Linked to Different Hormone Patterns
Some of the clearest differences appeared among men. Greater coffee consumption was associated with a more favorable glucose-insulin profile, higher levels of total and bioavailable testosterone, and greater concentrations of sex hormone-binding globulin (SHBG). However, free testosterone and the free androgen index were modestly lower.

The hormonal associations were less extensive in women. Higher coffee consumption was mainly associated with increased SHBG and lower measures of free androgens.
“Coffee is consumed by millions of people every day, yet we still know surprisingly little about how it relates to our metabolism and hormones. What stood out in our findings was a distinct hormonal signature that didn’t disappear even after we took into account BMI and lifestyle factors, with several of these associations differing between men and women,” says Luca Verroest, lead author of the study and Doctoral Researcher at the University of Oulu.
Hormones Could Offer a Clue to Coffee’s Health Links
The findings raise the possibility that hormonal pathways could help explain some of the previously observed relationship between coffee consumption and metabolic health. Because the research was observational, however, it cannot establish that drinking coffee directly caused any of the biological differences identified in the study.
The setting also makes the research especially relevant. Finland ranks among the world’s highest coffee-consuming countries, with average annual consumption of approximately 11.8 kilograms (26 pounds) per person.
Researchers say the results offer a starting point for studies designed to determine whether coffee itself produces these biological changes and, if so, which compounds may be responsible. Scientists are currently investigating these questions using animal models, with the longer-term aim of moving toward human intervention studies.
Additional research will be necessary before the findings can be used to shape dietary recommendations.
The study, “Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland Birth Cohort 1966 study,” was published in the European Journal of Nutrition.

Cancer immunotherapy has dramatically changed how doctors treat many forms of cancer, yet pancreatic cancer has remained particularly resistant to these advances. A major obstacle is the environment that develops around pancreatic tumors. These tumors often create a “cold” tumor microenvironment that blocks immune cells from launching an effective attack.
Researchers at the University of Chicago have now developed a new approach that could help overcome this problem. In a study published in Science Advances, the team used BifidoSumIL-2, an engineered strain of Bifidobacterium longum, a probiotic bacterium naturally found in the gut, to carry an immune-stimulating treatment directly into tumors.
In animal models, the therapy slowed the growth of pancreatic tumors by selectively activating T cells that fight cancer. Its effects became even stronger when researchers combined it with chemotherapy, radiotherapy or immunotherapy. The findings suggest that BifidoSumIL-2 could eventually provide a new way to improve how pancreatic tumors respond to treatment.
Using Bacteria to Deliver Cancer Therapy
“A big unmet medical need has been pancreatic cancer, and so that was going to be our mountain to climb,” said Ralph Weichselbaum, MD, the Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at the University of Chicago.
BifidoSumIL-2 was created to release a modified version of interleukin-2 (IL-2) once it reaches a tumor. IL-2 is a potent immune signaling molecule that activates T cells involved in attacking cancer. Conventional IL-2 treatment, however, can produce serious side effects and can also stimulate immune cells that actually weaken the antitumor response.
The researchers sought to avoid these problems by using SumIL-2, a modified form of IL-2 engineered to more precisely activate cancer-fighting T cells while reducing stimulation of regulatory T cells. They then placed SumIL-2 inside Bifidobacterium longum so that the therapeutic molecule could be concentrated within tumors instead of throughout the body.

Developing the treatment required scientists from several disciplines to work together, including specialists in microbiology, synthetic biology, oncology, and immunology.
“This was a highly interdisciplinary effort,” said Mark Mimee, PhD, Assistant Professor of Microbiology at the University of Chicago. “We had to bring together people who understand bacteria, people who understand tumors, and people who understand the immune system to make something like this possible.”
Why Bifidobacterium Can Target Tumors
Bifidobacterium offered the researchers an unusual advantage as a delivery system. The bacterium grows in anaerobic environments, meaning places with very little oxygen. Low oxygen levels are common inside many solid tumors, including pancreatic tumors, while healthy tissues generally contain more oxygen and are therefore less suitable for the bacteria.
“Bifidobacterium is an obligate anaerobe, so it doesn’t grow in the presence of oxygen,” Mimee said. When the bacteria are injected systemically, they are cleared from healthy tissues with abundant oxygen. Inside the low-oxygen regions of tumors, however, they can become active.
That preference allows the engineered bacteria to function as microscopic drug factories inside tumors. Once there, they produce SumIL-2 where the treatment is needed rather than broadly throughout the body. Researchers also noted that Bifidobacterium has shown a favorable safety profile in preclinical models and is already well known as a probiotic organism. It is commonly present in yogurt and is generally recognized as a safe, off-the-shelf probiotic.

Engineering the organism was not simple.
“Bifidobacterium is not the easiest organism to work with,” Mimee said. “It’s anaerobic, it grows slowly, and the genetic tools for manipulating it are much more limited compared to model bacteria like E. coli. A lot of the work was just figuring out how to reliably engineer it.”
Stronger Results With Combination Treatments
Tests in animal models showed that BifidoSumIL-2 preferentially gathered inside tumors, stimulated immune activity, and slowed the growth of pancreatic cancer. It also changed the tumor microenvironment in a potentially beneficial way by increasing the activity of cancer-fighting CD8+ T cells.
The results improved further when BifidoSumIL-2 was paired with established cancer treatments. Combining the bacterial therapy with chemotherapy, radiation therapy, or anti-PD-L1 immunotherapy led to better tumor control and longer survival than the individual treatments achieved on their own.
“This combination potential is one of the study’s most important findings; BifidoSumIL-2 not only works by itself — it works with radiotherapy, chemotherapy, and immunotherapy,” Weichselbaum said.
Despite the encouraging findings, BifidoSumIL-2 has not been tested in humans. Future research will need to examine its long-term safety, the possibility of effects outside the intended tumor, how long the immune response lasts, and whether the bacteria might eventually be given orally instead of through injection. The researchers also want to investigate whether the strategy can be combined with newer pancreatic cancer treatments, including KRAS inhibitors.
The Growing “Bugs as Drugs” Approach
The research adds to growing interest in a strategy known as “bugs as drugs.” By engineering probiotic bacteria to seek out tumors and produce therapies directly inside them, scientists may be able to concentrate powerful immune treatments where they are most useful while reducing unwanted effects elsewhere in the body.
The study, “Engineered probiotic Bifidobacterium for tumor-targeted pancreatic cancer therapy” was supported by funds from the Ludwig Foundation and the National Institutes of Health.
Additional authors include Jaehyun Lee, Kaiting Yang, Christina Nowicki, Wei Liu, Emile Naccasha, and Hua Liang from the University of Chicago; Zhichen Sun from the University of Texas Southwestern, Dallas; and Yang-Xin Fu from Tsinghua University, Beijing, China.
UChicago Medicine and the Biological Sciences Division continue to be at the forefront of cancer care and research. In April 2027, UChicago Medicine will open the AbbVie Foundation Cancer Pavilion, Chicago’s first freestanding cancer pavilion, to bring advanced diagnostics, innovative treatments, translational discoveries, and comprehensive support to patients and the community.

A new UC San Francisco-led study has identified a sharp increase in invasive breast cancer among Asian American women over the past two decades.
Breast cancer rates have climbed across nearly every Asian American ethnic group at a pace that exceeds increases seen in any other U.S. ethnic group. The trend is particularly pronounced among women under 50 and among those diagnosed with advanced disease or certain aggressive forms of breast cancer.
Breast Cancer Rates Are Climbing Quickly
The study, published in JAMA Network Open, found that breast cancer incidence rose by more than 3% annually in nearly every Asian American ethnic group examined. The increases were even greater among Chinese and Vietnamese women.
Native Hawaiian women already have some of the highest breast cancer rates among women in the United States. However, their rates increased by about 1% per year, substantially less than the increases observed among Asian American groups.
Researchers say greater use of breast cancer screening probably does not explain the trend. Screening tends to identify more cancers at earlier stages, yet the fastest increases occurred among cancers that had already spread.
One particularly concerning finding involved triple-negative breast cancer, which is considered the most aggressive subtype. Among Chinese American women, cases of triple-negative breast cancer increased by more than 6% each year between 2017 and 2022.

“These patterns are highly concerning from a disparities standpoint,” said senior author Scarlett Lin Gomez, PhD, professor of epidemiology and biostatistics at UCSF and co-leader of the Cancer Control Program at the UCSF Helen Diller Family Comprehensive Cancer Center. “They underscore why it is so important to move beyond treating Asian Americans, Native Hawaiians, and Pacific Islanders as a single population.”
A Closer Look at Breast Cancer Risk
To examine these trends, researchers analyzed about 150,000 invasive breast cancer cases diagnosed from 2000 through 2022. The data came from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program.
The analysis included nine specific Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations across 14 states. Together, those states are home to about two-thirds of the U.S. AANHPI population.
Historically, Asian American women, with the exception of Native Hawaiian women, have had lower breast cancer rates than non-Hispanic white women. That difference is now shrinking quickly. By 2022, breast cancer incidence among Asian American women under 50 had become comparable to the rate among white women of the same age group.
Why Breast Cancer Is Rising Remains Unclear
Researchers do not yet know what is driving the increase in breast cancer among women younger than 50.

Changes in reproductive patterns, diet, and other lifestyle factors may contribute to the trend, but the research team said those factors do not fully account for what they are seeing.
Some Asian American communities may also face risk factors that scientists have not yet identified. Researchers hope two UCSF-based projects, the CRANE breast cancer study and the ASPIRE cohort study, will help uncover additional explanations.
“Understanding why breast cancer is increasing so rapidly in these communities is critical,” Gomez said. “At the same time, we need to ensure that women across all Asian American, Native Hawaiian, and Pacific Islander communities have access to culturally appropriate education, screening, and timely follow-up care.”
Authors: Other UCSF authors are Meg McKinley, MPH; Katherine Lin, MPH; Iona Cheng, PhD; and Salma Shariff-Marco, PhD.
Funding: The Breast Cancer Research Foundation, the National Cancer Institute’s SEER Program, and the Surveillance Research Program Division of Cancer Control and Population Sciences of the National Cancer Institute.

DNA consists of long molecular chains that carry the genetic instructions needed for life. In genetic engineering, researchers cut DNA at carefully chosen locations and connect those pieces with other DNA sequences. This process supports a wide range of applications, including improved crop breeding, treatments for genetic diseases, and the creation of animal models used in drug development.
To efficiently connect short pieces of DNA, scientists rely on overhanging sequences called sticky ends. These exposed sections help DNA fragments bind to one another. Producing the right sticky ends, however, requires highly precise cutting at specific locations, something existing technologies do not always handle well.
Researchers in Japan have now developed a method that uses silver nanoparticles to cut and reconnect DNA at targeted sites. The technique produced DNA assembly efficiencies two to five times higher than those achieved with conventional restriction enzyme methods. The findings were published in Nucleic Acids Research.
Limitations of Conventional DNA Assembly
Standard methods for assembling long DNA molecules typically use restriction enzymes to make cuts and T4 DNA ligase to connect the resulting fragments. Restriction enzymes, however, can only recognize and cut certain DNA sequences. They also tend to produce sticky ends that are relatively short, which can reduce the efficiency of the joining process.
Seeking an alternative, a team led by Professor Hiroshi Abe and Assistant Professor Masahito Inagaki at Nagoya University, working with Professor Natsuhisa Oka at Gifu University, investigated whether chemical reactions could be used to cut DNA at selected locations instead of relying on restriction enzymes.
The researchers revisited a reaction first reported between 1990 and 1992 in which silver ions cut 3′-thiol-modified DNA at specific sites. They tested whether this reaction could be used to create useful sticky ends. Silver ions were effective at cutting the DNA, but they also attached nonspecifically and caused precipitation. As a result, only about 14% of the DNA could be recovered, far too little for practical applications.

Silver Nanoparticles Improve DNA Recovery
The team next replaced silver ions with silver nanoparticles. The researchers reasoned that nanoparticles could be separated from the reaction mixture through centrifugation, which could make it easier to recover the DNA afterward.
Initial experiments found that DNA cleavage efficiency reached about 50% at 70°C and almost 100% at 95°C within two hours. Those temperatures, however, can damage long DNA molecules, creating another obstacle for practical use.
To solve this problem, the researchers coated the nanoparticles with polyethylene glycol (PEG), a water-soluble polymer, to improve their stability and dispersion. The coating raised DNA cleavage efficiency from 36% without PEG to 92% with PEG at 37°C over 31 hours. “In the end, we optimized the conditions to a practical level and, under ambient temperatures, achieved PEG-modified cleaving efficiency above 91% at 50°C within just one to two hours,” stated Inagaki, the study’s first author.
The nanoparticle approach provided another important advantage. Unwanted DNA fragments remained attached to the nanoparticle surfaces, while the desired fragments containing sticky ends stayed in solution. This built-in purification effect raised the final DNA recovery rate from 14% to 98%.
Longer Sticky Ends Boost DNA Joining
Silver nanoparticles also allowed the researchers to produce DNA fragments with 8-base sticky ends, which are difficult to generate using conventional restriction enzymes. When the scientists used T4 DNA ligase to connect those fragments, joining efficiency was about twice as high as with traditional methods.

The improvement became even greater with longer overhangs. Using an 18-base overhang, the researchers achieved a joining efficiency of 44%. By comparison, a conventional 4-base overhang produced an efficiency of only 8%, giving the new approach a fivefold advantage.
To test whether the method could work in a practical biological setting, the team assembled a DNA fragment that encoded green fluorescent protein (GFP). They then introduced the assembled DNA into human HeLa cells. The cells successfully expressed GFP, confirming that the DNA had been assembled accurately.
Potential Uses in Gene Therapy and Synthetic DNA
Inagaki commented, “We believe this technology will be useful for synthesizing genomic DNA, with many possible applications in areas such as mRNA library establishment for cancer vaccines and gene therapy, as well as the development of artificial protein drugs and genome crops.”
The researchers now want to determine whether the technique can move beyond connecting just two DNA fragments at a time. He also explained the next step: “We have shown that two DNA fragments can be joined. Now, we need to confirm whether multiple fragments can be joined at the same time — a key step for building genome-scale DNA.”
This work was supported by the Japan Science and Technology Agency (JST) (JPMJCR18S1, JPMJCR23N1, JP25H00427, JP24H00737, JP22H02219, JP22K21346 International Leading Research), and Japan Agency for Medical Research and Development (AMED) [JP22gm0010008 (LEAP), JP25ak0101289, JP223fa827 (SCADA), JP243fa827032 (SCADA), JP23bm1223009, JP24ek0109697, JP25ama221315, JP25km0405209, JP25ama221230; JP23fk0210133) and Tanaka Kikinzoku Memorial Foundation [Precious Metals Research Grants 2021 Silver Award to M.I.]. Funding to pay the Open Access publication charges for this article was provided by the Japan Science and Technology Agency.