(Press-News.org) A study published today in the journal Cell marks the first reported instance of generative AI designing synthetic molecules that can successfully control gene expression in healthy mammalian cells. Researchers at the Centre for Genomic Regulation (CRG) created an AI tool which dreams up DNA regulatory sequences not seen before in nature. The model can be told to create synthetic fragments of DNA with custom criteria, for example: ‘switch this gene on in stem cells which will turn into red-blood-cells but not platelets.’
The model then predicts which combination of DNA letters (A, T, C, G) are needed for the gene expression patterns required in specific types of cells. Researchers can then chemically synthesise the roughly 250-letter DNA fragments and add them to a virus for delivery into cells.
As a proof-of-concept, the authors of the study asked the AI to design synthetic fragments which activate a gene coding for a fluorescent protein in some cells while leaving gene expression patterns unaltered. They created the fragments from scratch and dropped them into mouse blood cells, where the sequence fused with the genome at random locations. The experiments worked exactly as predicted.
“The potential applications are vast. It’s like writing software but for biology, giving us new ways of giving instructions to a cell and guiding how they develop and behave with unprecedented accuracy,” says Dr. Robert Frömel, first author of the study who carried out the work at the Centre for Genomic Regulation (CRG) in Barcelona.
The study could lead to new ways for gene-therapy developers to boost or dampen the activity of genes only in the cells or tissues that need adjusting. It also paves the way for new strategies to fine-tune a patient’s genes and make treatments more effective and reduce side effects.
The work marks an important milestone in in the field of generative biology. To date, advances in the field have largely benefited protein design, helping scientists create entirely new enzymes and antibodies faster than ever before. However, many human diseases stem from faulty gene expression that is cell-type specific, for which there might never be a perfect protein drug candidate.
Gene expression is controlled by regulatory elements like enhancers, tiny fragments of DNA which switch genes on or off. To fix faulty gene expression, researchers can comb through genomes looking for naturally-existing enhancers that happen to suit their needs, limiting themselves to the sequences evolution has produced.
AI-generated enhancers can help engineer ultra-selective switches that nature has not yet invented. They can be designed to have exactly the on/off patterns required in specific types of cells, a level of fine-tuning which is crucial for creating therapies that avoid unintended effects in healthy cells.
However, the development of AI models requires lots of high-quality data, which has been historically lacking for enhancers. “To create a language model for biology, you have to understand the language cells speak. We set out to decipher these grammar rules for enhancers so that we can create entirely new words and sentences,” explains Dr. Lars Velten, corresponding author of the study and researcher at the Centre for Genomic Regulation (CRG).
The authors of the study created huge volumes of biological data to build their AI model by carrying out thousands of experiments with lab models of blood formation. They studied both enhancers and transcription factors, proteins also involved in controlling gene expression.
Until now, scientists studying enhancers and transcription factors typically used cancer cell lines because they are easier to work with. The researchers worked with healthy cells instead because it’s more representative of human biology. Their work helped uncover subtle mechanisms that shape our immune system and blood cell production.
Over five years, the team synthesised more than 64,000 synthetic enhancers, each carefully designed to test different arrangements and strengths of binding sites for 38 different transcription factors. It’s the largest library of synthetic enhancers ever built in blood cells to date.
Once inserted into the cells, the team tracked exactly how active each synthetic enhancer became across seven stages of blood-cell development. They discovered that while many enhancers activate genes in one type of cell, they repress genes in another.
Most enhancers worked like a volume dial, turning gene activity up or down. Surprisingly, certain combinations acted like on/off switches. The scientists call this “negative synergy,” meaning two factors that usually turn a gene on individually could effectively shut that gene down when they occur together.
The data from the experiments was crucial in setting out the design principles of the machine learning model. Once the model had enough measurements of how each synthetic enhancer changed gene activity in real cells, it could predict new designs that yield on/off outcomes, even if these enhancers had never existed in nature.
The study was designed to determine if a technology can work in practice before committing to larger-scale research. The researchers have only scratched the surface. Both humans and mice have an estimated 1,600 transcription factors regulating their genomes.
The work was carried out by Lars Velten, Robert Frömel, Julia Rühle, Aina Bernal Martínez, Chelsea Szu-Tu and Felix Pacheco Pastor, all members of Lars Velten’s research group at the Centre for Genomic Regulation. Rosa Martinez Corral from the Barcelona Collaboratorium, a joint initiative between the CRG and EMBL-Barcelona, also took part. The research was funded by an ERC Starting Grant from the European Union and a grant of the Spanish National Agency for Research.
END
AI-designed DNA controls genes in healthy mammalian cells for first time
A study in Cell describes a powerful and precise new way of turning genes on or off in specific types of cells only
2025-05-08
ELSE PRESS RELEASES FROM THIS DATE:
Veterans with depression have increased risk of heart failure: Study
2025-05-08
U.S. veterans with depression had a 14% higher risk of heart failure, a new Vanderbilt University Medical Center-led study found, even after adjusting for traditional risk factors.
The study, “Depression and Heart Failure in U.S. Veterans,” was published May 8 in the journal JAMA Network Open.
Corresponding author Evan Brittain, MD, MSCI, professor of Medicine, said the study suggests implications for patient care.
“Patients and clinicians have another reason to screen for and treat depression in order to prevent potential future heart failure,” he said.
Brittain, who holds the Cardiology Division Directorship, noted the study is the largest ...
Maternal cardiometabolic risk factors in pregnancy and offspring blood pressure at ages 2 to 18
2025-05-08
About The Study: In this cohort study of 12,480 mother-offspring pairs, researchers found that pre-pregnancy obesity, gestational diabetes, and hypertensive disorders of pregnancy, alone or in various combinations, were prospectively associated with higher offspring blood pressure at an early age and with an increased rate of blood pressure change from age 2 to 18 years, with the most profound associations with diastolic blood pressure among female offspring and with systolic blood pressure among Black offspring. These findings suggest that ...
Depression and heart failure in US veterans
2025-05-08
About The Study: In this cohort study, depression among veterans was associated with an increased hazard of incident heart failure after controlling for demographic and cardiovascular risk factors. Higher incident heart failure rates in patients with depression remained consistent in an otherwise low-risk cohort.
Corresponding Author: To contact the corresponding author, Evan L. Brittain, MD, MSc, email evan.brittain@vumc.org.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2025.9246)
Editor’s Note: Please see the article for additional information, ...
Experiences of care and gaslighting in patients with vulvovaginal disorders
2025-05-08
About The Study: In this cross-sectional study, a patient-centered measure of adverse experiences in vulvovaginal care was developed. Participants reported common past experiences with gaslighting (a patient’s concerns are dismissed without proper evaluation) and substantial distress; they frequently considered ceasing care. There is an urgent need for education supporting a biopsychosocial, trauma-informed approach to vulvovaginal pain and continued development of validated instruments to quantify patient experiences.
Corresponding Author: To ...
Vitamin supplements slow down the progression of glaucoma
2025-05-08
A vitamin supplement that improves metabolism in the eye appears to slow down damage to the optic nerve in glaucoma. Promising results have been published in the journal Cell Reports Medicine. The researchers behind the study have now started a clinical trial on patients.
In glaucoma, the optic nerve is gradually damaged, leading to vision loss and, in the worst cases, blindness. High pressure in the eye drives the disease, and eye drops, laser treatment or surgery are therefore used to lower the pressure in the eye and thus slow down the disease. Unfortunately, however, the effect ...
Physics: Eggs less likely to crack when dropped side-on
2025-05-08
Eggs are less likely to crack when dropped on their side than when dropped vertically, finds research published in Communications Physics. Controlled trials simulating the ‘egg drop challenge’, a common classroom science experiment, found that the shell of an egg can better withstand an impact when dropped side-on.
The goal of the ‘egg drop challenge’ is for students to prevent an egg from cracking when dropped from a set height. A common belief is that an egg is stronger and less likely to crack when dropped vertically, with this assumption often ...
Study links maternal health risks during pregnancy to higher blood pressure in children
2025-05-08
Children born to mothers with obesity, gestational diabetes mellitus or a hypertensive disorder of pregnancy have higher systolic and diastolic blood pressure than children born to mothers without these risk factors, according to a new USC study. Among children whose mothers had at least one risk factor, blood pressure also rose more quickly between ages 2 and 18 compared to their peers. The findings, which suggest that blood pressure interventions could start as early as pregnancy, were just published in JAMA Network Open.
Across the ...
Building vaccines for future versions of a virus
2025-05-08
At a glance:
Researchers have created an AI tool called EVE-Vax that can predict and design viral proteins likely to emerge in the future.
For SARS-CoV-2, panels of these “designer” proteins triggered similar immune responses as real-life viral proteins that emerged during the pandemic.
EVE-Vax could give scientists valuable clues to help them develop vaccines that protect against future versions of rapidly evolving viruses.
Effective vaccines dramatically changed the course of the COVID-19 pandemic, preventing illness, reducing disease severity, and saving millions of ...
Incidence of several early-onset cancers increased between 2010 and 2019
2025-05-08
PHILADELPHIA – In the United States, breast, colorectal, endometrial, pancreatic, and kidney cancers are becoming increasingly common among people under age 50, according to a study published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR).
The findings may have implications for early-onset cancer prevention and screening efforts, the researchers noted.
Early-onset cancers, defined in this study as those diagnosed in individuals under age 50, are rising in incidence for reasons that remain unclear, according ...
The road to lenacapavir, a breakthrough HIV treatment
2025-05-08
In the hunt for a remedy, when the baton is passed from dedicated academic scientists to an innovative company to trusted community advocates, outcomes for society can be especially powerful.
Today, thanks to that sequence of contributions, the first HIV drug to offer long-lasting protection from infection — eliminating the need for people to take a daily pill — exists. For their role in ensuring that drug, lenacapavir, came to life and to market, the AAAS Mani L. Bhaumik Breakthrough of the Year Award is being awarded to Wesley Sundquist, chair of the University of Utah Department of Biochemistry; Moupali Das, vice president, Clinical Development, HIV Prevention ...
LAST 30 PRESS RELEASES:
School dinners may encourage picky teenagers to eat better, says new study
Study suggests loss of lung capacity begins between the ages of 20 and 25
California chief nurse officer recognized as national champion for women’s health
Dental and vision services among veterans in Medicare Advantage vs traditional Medicare
Under embargo: Mount Sinai experts to present new research on preeclampsia, doula care and more at 2025 2025 ACOG Annual Clinical and Scientific Meeting
Study reveals a deep brain region that links the senses
Bismuth’s mask uncovered: Implications for quantum computing and spintronics materials
Two HIV vaccine trials show proof of concept for pathway to broadly neutralizing antibodies
Ewell joins Gerontological Society of America’s Board of Directors
Large study traces prehistoric human expansion into South America, where genomic studies have been lacking
Millions of previously undocumented genetic variants discovered in Brazil’s highly admixed population
Limited evidence for “escalator to extinction” in mountain ecosystems under climate change
Asians made humanity’s longest prehistoric migration and shaped the genetic landscape in the Americas, finds NTU Singapore-led study
OHSU study reveals impact of oft-overlooked cell in brain function
World’s largest bat organoid platform paves the way for pandemic preparedness
Mapping the genome of the Brazilian population, with implications for healthcare
Proof of concept for Amsterdam UMC-led HIV vaccination
MSK researchers identify key player in childhood food allergies: Thetis cells
Link between ADHD and obesity might depend on where you live
Scientists find two brain biomarkers in long COVID sufferers may be what’s causing their brain fog, other cognitive issues
Empowering cities to act: The Climate Action Navigator highlights where climate action is most needed
KAIST's pioneering VR precision technology & choreography tool receives spotlights at CHI 2025
Recently, a joint Chinese–American research team led by Dr. HU Han from the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) of the Chinese Academy of Sciences and Dr. Jingmai O’Conno
Nationally recognized emergency radiologist Tarek Hanna, MD, named new chair of Diagnostic Radiology & Nuclear Medicine at the University of Maryland School of Medicine
“Chicago archaeopteryx” unveiled: New clues on dinosaur–bird transition revealed by Chinese–American research team
‘Rogue’ immune cells explain why a gluten-free diet fails in some coeliac patients
World's first patient treated with personalized CRISPR gene editing therapy at Children’s Hospital of Philadelphia
Infant with rare, incurable disease is first to successfully receive personalized gene therapy treatment
Digital reconstruction reveals 80 steps of prehistoric life
GSA and GSA Foundation announce record support for the geosciences
[Press-News.org] AI-designed DNA controls genes in healthy mammalian cells for first timeA study in Cell describes a powerful and precise new way of turning genes on or off in specific types of cells only