PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

New insights into long-term dysfunction of edited blood stem cells and how to overcome it

At the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), Milan, scientists uncover senescence as an unexpected side effect of CRISPR gene editing and propose solutions to improve therapeutic outcomes

2025-06-03
(Press-News.org)

Scientists at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, have found that gene editing using CRISPR-Cas9 in combination with AAV6 vectors can trigger inflammatory and senescence-like responses in blood stem cells, compromising their long-term ability to regenerate the blood system. The study, published in Cell Reports Medicine, outlines new strategies to overcome this hurdle, improving both the safety and efficacy of gene-editing-based therapies for inherited blood disorders.

The research was led by Dr. Raffaella Di Micco, group leader at SR-Tiget, New York Stem Cell Foundation Robertson Investigator and Associate Professor at the School for Advanced Studies (IUSS) of Pavia, in collaboration with Professor Luigi Naldini, Director of SR-Tiget, and several European research partners.

Unmasking senescence as an hidden challenge in gene editing.

Homology-directed repair (HDR)-based gene editing in hematopoietic stem and progenitor cells (HSPCs) holds great promise for the treatment of genetic blood diseases. Despite significant advances in HDR-based gene editing, translating these approaches into safe and effective clinical therapies for patients remains a major challenge. While the technology shows strong potential in laboratory settings, achieving reliable, durable outcomes in human hematopoietic stem cells - without compromising their function - has indeed proven difficult. The team of Di Micco at SR-Tiget discovered that CRISPR-Cas9 editing, especially when using AAV6 vectors to deliver the repair template, activates a strong DNA damage response (DDR) and inflammatory signals driven by p53 and IL-1/NF-κB pathways.This leads to inflammation and a senescence-like state that reduces the the regenerative capacity of the edited cells post-transplantation.

“We found that a fraction of gene-edited hematopoietic stem cells shows signs of premature aging,” explains Dr. Di Micco. “This reduces their ability to regenerate blood cells after transplantation, which can limit the long-term success and therapeutic benefit of gene therapy.”

We were surprised by the persistence of senescence-like features even months after transplantation,” says Dr. Anastasia Conti, first author of the study and Project Leader in Dr. Di Micco’s lab. “Our findings suggest that stem cells retain a ‘memory’ of the genetic engineering process. These adverse effects are not just transient stress responses—they can lead to lasting impairments in stem cell function.

Mitigating senescence for superior performance of genetically-engineered cells:

To counteract this adverse effect, the researchers tested two complementary strategies:transient p53 inhibition and the use of anti-inflammatory agents, particularly Anakinra - a clinically approved IL-1 receptor antagonist.

“Both approaches significantly reduced senescence markers in edited HSPCs and improved their ability to regenerate a healthy, diverse blood system in preclinical models. Importantly, Anakinra also reduced potential genotoxic events, such as large deletions and translocations, suggesting a safer profile compared to p53 inhibition alone” says Dr. Conti.

“Our study shows that modulating the inflammatory and senescence-related response during gene editing can preserve the fitness of edited hematopoietic stem cells and enable more stable and polyclonal hematopoietic reconstitution in the long-term. These findings help explain setbacks observed in recent clinical trials involving HDR-based gene editing in blood stem cells and offer a concrete path to enhance outcomes. The strategies proposed could be especially valuable for diseases requiring long-term correction and stem cell engraftment, such as immunodeficiencies or bone marrow failure syndromes” concludes Dr. Di Micco.

This groundbreaking research was conducted in the Di Micco Lab with support from the European Research Council (ERC), the European Innovation Council (X-PAND), and the New York Stem Cell Foundation. With a longstanding history of pioneering gene therapy technologies, SR-Tiget continues to lead international efforts to optimize CRISPR-based treatments for safe clinical translation.

 

END



ELSE PRESS RELEASES FROM THIS DATE:

Severe maternal morbidity by race and ethnicity and birth mode

2025-06-03
About The Study: In this cross-sectional study of births among individuals with a prior cesarean birth, patterns of severe maternal morbidity (SMM) by birth mode varied by race and ethnicity, with elevated rates of SMM among those from marginalized racial and ethnic groups with planned cesarean births. Future work should identify interventions to improve quality of care and promote equity for this population. Corresponding author: To contact the corresponding author, Laura B. Attanasio, Ph.D., email lattanasio@umass.edu. To access ...

Individual- and area-level incarceration and mortality

2025-06-03
About The Study: In this cohort study of 3.26 million individuals in the U.S., results highlighted the dual burden of incarceration on health outcomes. Individuals who were incarcerated faced significantly higher risks of death, particularly from overdoses, and elevated county incarceration rates exacerbated individual-level mortality risks. These findings suggest the need for reforms in criminal justice and public health policies to address these elevated risks and their widespread implications. Corresponding author: To contact the corresponding author, Utsha G. Khatri, M.D., M.S., email utsha.khatri@mountsinai.org. To access the embargoed study: ...

New tool to generate aneuploidies and analyze their impact on development

2025-06-03
Barcelona, 3 June 2025 - More than 80% of early human embryos contain cells with an incorrect number of chromosomes—a phenomenon called aneuploidy. This typically stems from errors in chromosome segregation during the very first cell divisions. Remarkably, aneuploid cells are eliminated before implantation. When this does not happen, aneuploidy causes miscarriages or developmental disorders. Understanding how aneuploid cells are eliminated in these early stages is crucial for gaining insights into fertility, and it could also have implications for diseases like cancer. A team led by Dr. Marco Milán at IRB Barcelona has developed a tool that can generate customized ...

SwRI-led research finds particles energized by magnetic reconnection in the nascent solar wind

2025-06-03
SAN ANTONIO — June 3, 2025 — New research led by a Southwest Research Institute scientist identified a new source of energetic particles near the Sun. These definitive observations were made by instruments aboard NASA’s Parker Solar Probe, which detected the powerful phenomena as the spacecraft dipped in and out of the solar corona. These new results offer fresh perspectives on how magnetic reconnection could heat the solar atmosphere, which then transitions into the solar wind, and also how solar flares accelerate a small fraction of charged particles to ...

Aging increases brain’s sensitivity to hypoxia and blood-brain barrier damage in mice

2025-06-03
“As advanced age is associated with increased incidence of hypoxia-associated conditions such as asthma, emphysema, ischemic heart disease, heart failure, and apnea, our findings have important implications for many people.” BUFFALO, NY — June 3, 2025 — A new research paper was published in  Aging (Aging-US) on May 1, 2025, as the cover of Volume 17, Issue 5, titled “Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age.” In this ...

Eating more phytosterols could lower your risk of heart disease and diabetes

2025-06-03
Heart disease and type 2 diabetes rank among the leading causes of death and disability in the United States, and eating a healthy diet rich in plant-based foods can help to prevent or delay both of these conditions. New research suggests that a particular component of plant-based foods, known as phytosterol, could be instrumental in lowering the risk.   According to the study, people who consumed more phytosterol—a compound structurally similar to cholesterol found in some plant foods—had a significantly lower risk of both heart disease and type 2 diabetes. Higher phytosterol intake was also associated with markers of better insulin regulation and reduced inflammation, ...

Eating more sweet food may not sway sweet preference

2025-06-03
Turns out, your sweet tooth may not be shaped by your diet. Findings from a new randomized controlled trial suggest that eating more sweet-tasting foods doesn’t increase someone’s preference for sweet tastes.   The researchers found that after six months on diets with varying amounts of sweet foods, study participants' preference for sweetness stayed the same, no matter how much sweet-tasting foods they ate.   “We also found that diets with lower or higher dietary sweetness ...

Scientists propose new approach for classifying processed foods

2025-06-03
Recent years have seen growing scrutiny and debate around processed foods, but researchers have struggled to pin down what aspects of food processing are most relevant to health. Now, scientists have developed a system for classifying processed foods based on information about the health impacts associated with particular ingredients.   The new approach was developed by WISEcode, creator of an app that provides consumers with information about the food ingredients found in packaged goods.   “WISEcode’s approach is more nuanced and objective than previous classification ...

New study: Daily mango intake may support postmenopausal heart and metabolic health

2025-06-03
ORLANDO, Fla., June 3, 2025 – Each year, 1.3 million women enter menopause—a life stage during which heart disease risk rises significantly. Nearly half of American women are affected by cardiovascular disease, and since women spend up to 40% of their lives postmenopausal, managing heart health is especially important. A new study published in the Journal of the American Nutrition Association found that eating about two servings of mangos daily for two weeks (330 g, about 1.5 cups) significantly ...

Study finds daily cup of beans boosts heart and metabolic health

2025-06-03
A new study suggests that regularly eating a cup of beans a day may offer measurable benefits for heart and metabolic health. Incorporating beans into daily diets could serve as a simple, cost-effective way to reduce the risk of chronic diseases.   The 12-week study of 72 people with prediabetes showed an association between chickpea consumption and improved cholesterol levels, while eating black beans was linked with reduced inflammation.   "Individuals with prediabetes often exhibit ...

LAST 30 PRESS RELEASES:

Weight stigma—not BMI—has the biggest effect on mental health after weight-loss surgery

Research alert: Alzheimer's gene therapy shows promise in preserving cognitive function

New York Eye and Ear Infirmary of Mount Sinai opens first Comprehensive Center for Refractive Solutions in New York

Storm ready: FAU Sensing Institute’s weather network delivers real-time forecasting

UChicago receives $21 million to establish visionary center in quantum engineering and health

Inherited genetic trait predicts resistance to immunotherapy for deadly skin cancer

Oxford physicists recreate extreme quantum vacuum effects

Talking therapy could be effective treatment for stroke survivors

A new method for studying mechanical proteins and their involvement in muscular disorders

Two big events shaped the herbivores during 60 million years but their role remains

TU Graz study: front brake lights could significantly reduce the number of road accidents

A new mathematical model helps European regions set suitable targets to close gender gaps in education

Rapid testing for sexually transmitted infections on the horizon

Tech sector emissions, energy use grow with rise of AI

Smithsonian research reveals that probiotics slow spread of deadly disease decimating Caribbean reefs

Fungal resistance in wheat: preserving biodiversity for food security

’Round midnight: Late-night romance among medaka in near natural setting

Why seismic waves spontaneously race inside the earth

Survival of the greenest: Why world’s oldest organizations are surpassing young upstarts in environmental sustainability

Have female earwigs evolved their forceps as weapons in battles for mates?

Baby's microbiome may protect against childhood viral infection

Diabetes drug shows benefits for patients with liver disease

P2Y12 drugs may be better than aspirin to prevent heart attack and stroke in patients with coronary artery disease

Long-term data show sustained efficacy and safety of zigakibart in patients with IgA nephropathy

Landmark study reveals survival limits of kidney transplantation in older and high-risk patients

Targeting mitochondria to fight leukemia: Rice University-led research team pursues new treatment strategies

Antibiotics taken during pregnancy may reduce preterm births

Vigilance and targeted public health measures are essential in the face of the diphtheria epidemic that has affected vulnerable populations in Western Europe since 2022

New study: Personalized exercise boosts health for people with neuromuscular disease

FAMU-FSU College of Engineering researchers discover universal law of quantum vortex dynamics

[Press-News.org] New insights into long-term dysfunction of edited blood stem cells and how to overcome it
At the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), Milan, scientists uncover senescence as an unexpected side effect of CRISPR gene editing and propose solutions to improve therapeutic outcomes