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Tag: Gene

  • Gene Editing Nears an End to Daily Cholesterol Meds

    Gene Editing Nears an End to Daily Cholesterol Meds

    A new one-time CRISPR treatment targeting “bad” cholesterol will enter Phase I human trials. If it works, it could become the first approved gene-silencing therapy, removing the need for lifelong drugs and significantly cutting cardiovascular risk.
    Image Credits: New therapy targets the liver’s PCSK9 gene to lower cholesterol
    Depositphotos

    A new one-time CRISPR treatment targeting “bad” cholesterol will enter Phase I human trials. If it works, it could become the first approved gene-silencing therapy, removing the need for lifelong drugs and significantly cutting cardiovascular risk.

    Strong expectations surround Scribe Therapeutics’ STX-1150, a US-developed therapy that lowers LDL (“bad”) cholesterol by epigenetically silencing the PCSK9 gene in the liver. Although Verve Therapeutics tested a similar approach in 2023 and CRISPR Therapeutics developed the more recent CTX310, both candidates are still undergoing clinical trials.

    STX-1150 targets hypercholesterolemia, a major driver of atherosclerotic cardiovascular disease (ASCVD). Rather than permanently altering DNA, it reduces LDL-C by temporarily switching off PCSK9 through epigenetic mechanisms.

    A Reversible Gene-Silencing Approach for Cholesterol

    Scribe CEO Dr. Benjamin Oakes says the therapy tackles the shortcomings of current cholesterol treatments and could transform cardiovascular risk management for millions.

    Rather than cutting or permanently changing DNA, STX-1150 works by adding regulatory modifications and DNA methylation marks to the PCSK9 gene in liver cells, switching off its activity in a way that can be reversed if necessary.

    Although CRISPR has made rapid progress, it is still a young technology in medicine. Major advances emerged around 2019, followed by the first successful use of CRISPR to treat a baby with a previously incurable genetic disorder. In 2024, the US Food and Drug Administration approved a landmark CRISPR/Cas9 therapy for sickle cell disease, highlighting the pace at which the field is moving. Despite this promise, precision gene therapies continue to face significant regulatory and ethical hurdles.

    Cost and Availability Continue to Pose Challenges

    Access and affordability remain major concerns as well. The sickle cell treatment Casgevy carries an estimated price tag of US$2.2 million per patient, putting it beyond the reach of most people. While an effective cardiovascular gene therapy could eliminate the long-term costs of managing conditions like high LDL cholesterol, it is still unclear whether the roughly 70 million Americans with chronically elevated cholesterol would be able to access such a one-time treatment if it gains approval.

    That said, penicillin was also extremely expensive when it was first introduced in 1940, costing the equivalent of about $400 per dose. An approved CRISPR therapy for lowering LDL cholesterol could similarly pave the way for broader access over time, becoming the first of many treatments that gradually transform affordability. After all, biotechnology and personalized medicine are widely seen as the future of healthcare—we just need to reach that point.

    “Bringing STX-1150 into the clinic marks a pivotal milestone for Scribe and for the genetic medicine field as a whole,” Oakes said. “Scribe has been developing CRISPR-based therapies with the strength, precision, and long-lasting effects needed to raise the standard of care, especially for large cardiometabolic patient populations.”

    Reed the original article on: New Atlas

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  • Bird Flu Has a Heat-Resistant Gene That Helps it Survive Fever Defenses

    Bird Flu Has a Heat-Resistant Gene That Helps it Survive Fever Defenses

    Scientists have found that avian flu viruses carry a gene that makes them unusually tolerant to heat, rendering one of our key immune defenses—fever—largely ineffective. Instead of slowing the infection, higher temperatures actually help these viruses reproduce.
    Bird flu viruses have a genetic component in their “engine” that keeps them running – and replicating – even when our bodies turn up the heat 
    Image Credits: Depositphotos

    Scientists have found that avian flu viruses carry a gene that makes them unusually tolerant to heat, rendering one of our key immune defenses—fever—largely ineffective. Instead of slowing the infection, higher temperatures actually help these viruses reproduce.

    Researchers at the University of Cambridge and the University of Glasgow have shed new light on why bird flu poses a greater threat to humans than seasonal influenza A. The difference appears to hinge on a single heat-protective gene called BP1.

    Why Avian Influenza Thrives Where Human Flu Struggles

    Fever is an ancient mammalian defense mechanism that raises body temperature just enough to hinder the growth of many pathogens, including typical influenza A. Seasonal flu viruses adapted to humans grow best in the cooler temperatures of the upper respiratory tract (around 33 °C / 91 °F) and weaken quickly as temperatures near 40 °C (104 °F).

    Birds, however, naturally maintain much higher body temperatures—between 40 °C and 42 °C (104–108 °F). Avian influenza viruses, including the dangerous strains that occasionally infect humans, have evolved to replicate efficiently in these hotter conditions.

    The researchers set out to determine whether this heat-tolerance trait helps explain why avian influenza causes such severe disease when it infects humans. To test this, they engineered two nearly identical viruses that differed only in their PB1 gene—the “engine” the virus relies on to replicate.

    How a Single Gene Alters Virus Behavior Under Fever Conditions

    One virus carried PB1 from a human-adapted strain, which breaks down at fever-level temperatures; the other carried PB1 from avian influenza strains, including those present in the 1957 and 1968 pandemic viruses.

    This single genetic swap dramatically changed how the viruses behaved, a pattern first seen in cell cultures and later confirmed in mice. At normal temperatures, both versions made the animals seriously ill. Because mice rarely develop fevers in response to flu, the researchers warmed the animals’ environment, raising their core temperature by about 2 °C (3.6 °F).

    In this warmer setting, the human-adapted virus struggled—it couldn’t operate properly or replicate, leading to only mild symptoms. The avian-PB1 virus, however, showed no such weakness: it replicated efficiently and caused severe disease, just as it did in mice kept at normal body temperatures.

    “This elegant study builds on the simple insight that animals maintain different body temperatures, and demonstrates how that can shape the way viruses behave when they jump between species,” said Professor Wendy Barclay, Chair of the Medical Research Council (MRC) Infections and Immunity Board. “The researchers show that human-adapted influenza viruses replicate poorly when temperatures rise, as happens during fever. In contrast, avian influenza viruses—accustomed to the higher body temperatures of their natural bird hosts—are not restrained by the fever response when they infect mammals.”

    PB1 Gene Reassortment

    As noted, the most lethal influenza outbreaks of the 20th century involved viral strains whose PB1 gene originated in birds—a fact revealed through extensive genetic sequencing. Influenza A contains eight separate gene segments, and when two strains infect the same cell, they can exchange these segments through reassortment. PB1 is one of the segments most likely to jump between human and avian viruses during this mixing process.

    “The capacity of flu viruses to trade genes remains a major driver of risk for emerging strains,” explained Dr. Matt Turnbull, lead author from the Medical Research Council Centre for Virus Research at the University of Glasgow. “We’ve seen this happen in earlier pandemics, like those in 1957 and 1968, when a human influenza virus acquired its PB1 gene from an avian strain. That may help explain why those pandemics produced such severe disease.”

    The new research suggests that this small gene might have enabled those pandemic viruses to bypass the human body’s temperature-based defenses, allowing them to cause such widespread and serious illness—and it underscores the potential danger should an avian flu virus successfully jump into humans again.

    “It’s essential to keep a close watch on bird flu strains so we can better prepare for possible outbreaks,” said Turnbull. “Assessing how resistant these viruses are to fever could help us pinpoint the strains most likely to cause severe disease.”

    Rare but Deadly

    Recently, a resident of Washington died from complications after being infected with a novel avian influenza strain not previously seen in humans. While bird flu viruses have not yet become efficient at spreading between people, human infections, though rare, tend to be severe.

    “Fortunately, human infections with bird flu remain uncommon, but we still see several dozen cases each year,” said senior author Professor Sam Wilson from the Cambridge Institute of Therapeutic Immunology and Infectious Disease. “Historically, bird flu infections in humans have had alarmingly high fatality rates, such as with H5N1, which caused over 40% mortality.”

    “Grasping why bird flu viruses trigger severe illness in humans is vital for effective monitoring and pandemic preparedness,” Wilson added. “This is particularly critical given the pandemic risk posed by avian H5N1 strains.”

    Read the original article on: New Atlas

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  • Mouse Created Using Gene Older Than Animal Life

    Mouse Created Using Gene Older Than Animal Life

    Credit: Pixabay

    Scientists have created a hybrid mouse by incorporating a gene that predates all animal life. In this groundbreaking study, the team replaced a single gene in the mouse stem cells with one from an ancient, single-celled ancestor and successfully grew healthy mice from it.

    Stem cells are known for their ability to differentiate into various cell types. In 2006, Japanese scientists discovered how to reprogram mature cells into stem cells, known as induced pluripotent stem cells (iPSCs). This breakthrough has opened doors to potential regenerative therapies.

    The original team found that iPSCs could be created by modifying just four genes, now known as Yamanaka factors. In this new study, researchers from Queen Mary University of London and the University of Hong Kong replaced one of these genes in the mouse with a much older version from choanoflagellates, single-celled organisms that are the closest relatives to the ancestors of animals.

    Although choanoflagellates do not use stem cells, they possess some of the same genes that animals use for stem cell functions. The researchers wanted to test whether these ancient genes could serve the same purpose in modern stem cells.

    Researchers Create Hybrid Mouse iPSCs by Replacing Sox2 with Ancient Gene from Choanoflagellates

    To begin, the researchers created mouse iPSCs using the standard method, with one modification: they swapped out Sox2, one of the Yamanaka factors, with the corresponding gene from choanoflagellates. These “hybrid” iPSCs were then injected into a developing mouse embryo.

    To confirm the success of the experiment, the researchers engineered the iPSCs to produce distinct traits, such as dark eyes and black fur patches. As a result, the mouse that developed from the embryo was a chimera, showing these traits alongside those from the original embryo.

    This remarkable finding demonstrates that the genes responsible for stem cell functions were likely in use long before stem cells were first discovered. The researchers suggest that choanoflagellates may have originally used these genes to regulate basic cellular functions, and that multicellular organisms later adapted them for stem cell purposes.

    “By creating a mouse using genes from our single-celled relatives, we observe an extraordinary continuity of function across nearly a billion years of evolution,” said Alex de Mendoza, the study’s corresponding author. “Our study suggests that genes crucial to stem cell formation may have originated long before stem cells themselves, possibly paving the way for the emergence of multicellular life.”

    The researchers believe this discovery could contribute to advancements in regenerative medicine.

    Read Original Article: New Atlas

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