Radically different
Last summer, Bain Capital Life Sciences announced that it would form a new biotech startup, created with $300 million and five drugs licensed from Bristol Myers Squibb.
Now that company has a name, a CEO, and a mission.
The venture, Beeline Medicines, will continue development of five inflammatory and immune disorder drugs, starting with a potential daily pill for lupus. Beeline plans to report data from a Phase 2 trial of that drug later this year.
File this under “hiding in plain sight.”
Last fall, the Journal of the American Academy of Child & Adolescent Psychiatry issued a so-called expression of concern about a controversial study that was published in 2001 about the widely prescribed antidepressant known as Paxil.
Such a step is taken when a study may have errors or include unreliable information. The notice, which followed a request for a retraction, indicated that a review was underway. Meanwhile, it served as a warning, of sorts, to health care providers who might consult the study when deciding whether to prescribe the medicine.
Around half the outputs from five commonly used artificial intelligence (AI) chatbots could lead users to ineffective or harmful medical choices without professional guidance, suggests research led by the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center.
As reported in BMJ Open, the researchers tested the free web versions of Gemini, DeepSeek, Meta AI, ChatGPT 3.5 and Grok available in 2024. They created 50 different adversarial prompts intended to test whether the AI models would give a problematic response or not.
The prompts were intended to realistically represent the kinds of queries members of the public might enter about health topics ranging from cancer to vaccines to stem cells, nutrition, and athletic performance. Some prompts required a specific answer and some were more open.
The researchers collected 250 responses to their prompts and categorized them as non-, somewhat, or highly problematic, using pre-defined criteria. Around 50% were problematic, 30% somewhat problematic and 19.6% highly problematic. Open-ended prompts received the most problematic answers.
In terms of the specific models, Grok produced a disproportionate share of highly problematic answers, while Gemini produced the fewest highly problematic and the most non-problematic responses. Topic-wise, the chatbots appeared more accurate when asked about cancer and vaccines, but less so when asked about stem cells, athletic performance, and nutrition.
Reference lists provided to users by the models were limited or inaccurate and the answers required some knowledge to interpret properly and were aimed at college-educated users.
“Despite adversarial pressure, chatbots typically responded in a confident, authoritative tone. Refusals to answer and explicit caveats or disclaimers were rare, reflecting the models’ strong tendency to provide an output even when prompts steered toward contraindicated advice,” write lead author Nicholas Tiller, PhD, a research associate at the Lundquist Institute, Harbor-UCLA Medical Center, and colleagues.
“As the use of AI chatbots continues to expand, our data highlight a need for public education, professional training and regulatory oversight to ensure that generative AI supports, rather than erodes, public health,” they conclude.
The post Popular AI Chatbots Can Provide Misleading Medical Information appeared first on Inside Precision Medicine.
Regeneron Pharmaceuticals plans to expand its pipeline into radiopharmaceutical therapies through an up to $4.3 billion collaboration with Telix Pharmaceuticals to co-develop and co-commercialize precision oncology treatments and companion diagnostics.
The companies have agreed to partner on next-generation radiopharmaceutical therapies aimed at up to eight solid tumor targets from Regeneron’s portfolio of antibodies, generated from VelocImmune® technology, which uses the company’s own mouse platform engineered with a genetically humanized immune system.
Regeneron and Telix also said they plan to develop radio-diagnostics designed to support patient selection and treatment response assessment.
The collaboration is intended to combine the biologics expertise of Tarrytown, NY-based Regeneron, including bispecific antibody discovery, with the radiopharmaceutical development platform, global manufacturing capabilities, and supply chain infrastructure of Telix, which is headquartered in Melbourne, Australia.
“Regeneron is excited to enter the targeted radiopharmaceuticals space and explore the utility of these agents either as monotherapy or rationally combined with our immunotherapy platform, particularly in areas of high unmet patient need such as lung cancer, where our PD-1 inhibitor is a global standard of care,” Israel Lowy, MD, PhD, Regeneron’s senior vice president and clinical development unit head, oncology, said in a statement.
Lowy referred to Libtayo® (cemiplimab-rwlc), a programmed death receptor-1 blocking antibody approved for multiple oncology indications including forms of non-small cell lung cancer (NSCLC), as well as cutaneous squamous cell carcinoma, and basal cell carcinoma. Libtayo finished 2025 with $1.453 billion in worldwide net product sales, up 19% from $1.217 billion in 2024. Figures include $425 million in Q4 2025 global net product sales, up 16% from $367 million in the year-ago quarter.
“In our view, the deal with Regeneron validates Telix’s differentiated capabilities in radiopharmaceutical development and handling of complex supply chain logistics,” Andy T. Hsieh, PhD, a partner and biotechnology analyst with William Blair, wrote Monday in a research note. “Furthermore, given Regeneron’s track record of developing successful commercial therapeutics, we believe it is an ideal partner in bringing forth antibody-based theranostic assets.”
Telix investors appeared to somewhat agree with that analysis. The company’s ordinary shares traded on the Australian Stock Exchange climbed nearly 8% from A$14.64 ($10.34) to A$15.77 ($11.13). Telix’s American depositary shares traded on NASDAQ rose about 7%, from $10.56 to $11.24.
Hsieh reiterated William Blair’s “Outperform” rating for Telix shares based on several potential value-creating inflection points, including:
The FDA rejected both Zircaix and Pixclara last year via separate complete response letters. The agency held in April 2025 that Zircaix required additional confirmatory clinical evidence, which the company agreed to provide. On Friday, Telix said the FDA accepted its resubmitted New Drug Application (NDA) for Pixcara, assigning a target decision date of September 12 under the Prescription Drug User Fee Act (PDUFA).
In August 2025, the FDA rejected Zircaix via complete response letter, alleging deficiencies relating to its chemistry, manufacturing, and controls (CMC) package—deficiencies the company said were “readily addressable.”
“We look forward to additional updates pertaining to efficacy parameters, such as progression-free survival, an approvable endpoint, likely later this year,” Hsieh added.
Telix has built up its radiopharma infrastructure in recent years through acquisitions, spending $13.6 million to purchase IsoTherapeutics, a contract development and manufacturing organization (CDMO) focused on providing services to Telix and other radiopharmaceutical companies—followed by an up to $82 million buyout of radioisotope production technology firm ARTMS, which stands for alternative radioisotope technologies for medical science.
In September 2024, Telix expanded its manufacturing footprint by acquiring RLS Radiopharmacies for up to $250 million, part of an investment strategy focused around creating vertically integrated supply chain, manufacturing, and distribution.
The global radiopharmaceuticals market is predicted to grow at a compound annual growth rate of 10.1%, more than doubling from $14.2 billion this year to $31 billion in 2032, then soaring again to $54.6 billion by 2040, according to a Roots Analysis report issued in January.
Telix briefly pursued a U.S. initial public offering, which it withdrew in June 2024. The company cited market conditions as biotech IPOs met with chilly receptions on Wall Street and asserted that the offering was not predicated on the need to raise capital.
Regeneron has agreed to pay Telix $40 million in upfront cash for access to its radiopharmaceutical manufacturing platform for four initial therapeutic programs, with Regeneron holding an option to expand the collaboration to include four additional programs with additional upfront payments.
Telix and Regeneron have agreed to share equally their global commercialization costs and potential profits, with Telix retaining the option to co-promote certain potential products. However, if Telix were instead to opt out of the co-funding model for any of the original four programs, it would then be eligible to receive up to $535 million in development and commercial milestone payments, plus low double-digit royalties on future net sales, for that program.
If Telix opts out of co-funding for all four, company could achieve $2.14 billion in payments tied to achieving milestones.
For the diagnostics to be covered by the collaboration, Telix and Regeneron have agreed to jointly develop diagnostic assets, with Telix leading commercialization and Regeneron receiving a set percentage of profits.
“The collaboration with Regeneron reflects a highly complementary set of capabilities and a unique opportunity to explore what true ‘next gen’ biologics-based radiopharmaceuticals can potentially do for patients,” added Christian Behrenbruch, DPhil, managing director and group CEO at Telix. “We are well positioned to work toward the shared goal of advancing next-generation precision radiopharmaceuticals for patients with hard-to-treat cancers.”
The post Regeneron, Telix Launch Up-to-$4.3B Cancer-Focused Radiopharma Drug, Diagnostic Collaboration appeared first on GEN – Genetic Engineering and Biotechnology News.
Studying mice, researchers at Toronto’s Sinai Health have found that semaglutide—the active ingredient in popular weight loss drugs that mimic the gut hormone GLP-1—acts directly on a subset of liver cells to improve organ function, and does so independently of weight loss. The finding challenges long-held assumptions about how GLP-1 medicines work in the liver and could reshape how physicians treat metabolic liver disease.
Headed by Daniel Drucker, MD, a senior investigator at the Lunenfeld-Tanenbaum Research Institute, the team reported on their findings in Cell Metabolism, in a paper titled “The weight-loss-independent hepatoprotective benefits of semaglutide are orchestrated by intrahepatic sinusoidal endothelial GLP-1 receptors.”
For years, the liver benefits of semaglutide have puzzled scientists. “Glucagon-like peptide-1 (GLP-1) medicines improve metabolic liver disease through weight-loss-dependent and -independent actions,” the authors wrote. The drug was known to lower blood sugar and promote weight loss, but patients’ livers were improving in ways that those effects alone could not explain. And as the authors further noted, “The therapeutic scope of GLP-1 medicines extends beyond glycemic control and weight loss, with benefits evident in people with atherosclerotic heart disease, heart failure with preserved ejection fraction (HFpEF), peripheral artery disease, diabetic kidney disease, knee osteoarthritis, and obstructive sleep apnea (OSA).” However, as the team further pointed out, “… the mechanisms by which GLP-1 medicines improve organ dysfunction remain incompletely understood.”
Drucker has been at the forefront of GLP-1 research since the 1980s when his pioneering discoveries helped lay the groundwork for the development of GLP-1 medicines. After transforming treatment of type 2 diabetes and obesity, semaglutide and other GLP-1 medicines have been approved for other conditions including MASH (metabolic dysfunction-associated steatohepatitis). MASH is a severe form of fatty liver disease in which fat build-up, inflammation, and tissue scarring can lead to cirrhosis and liver failure. It affects about 25% Canadian adults and because it is closely linked with obesity and type 2 diabetes, treatment typically includes lifestyle interventions to reduce weight. “The approval of semaglutide for MASH highlights the importance of understanding the hepatoprotective mechanisms of GLP-1 action,” the investigators stated.
Drucker and colleagues have now found that semaglutide acts directly on the liver to reduce inflammation and scarring and improve organ function in a way that is independent of weight loss. Their finding overturns a prevailing assumption in the field that liver cells do not carry the receptor that semaglutide binds to, meaning the drug had no direct route to the organ.
Postdoctoral researcher Maria Gonzalez-Rellan, PhD, spearheaded the work that combined sophisticated mouse models of MASH with deep molecular analyses of liver cells. Her work identified two cell types carrying semaglutide receptors: liver sinusoidal endothelial cells (LSECs) and immune T cells. Although LSECs account for only about 3% of liver cell volume, they proved to be the key driver of semaglutide’s liver benefits.
![A pioneer in GLP-1 biology Dr. Daniel Drucker has dedicated his career to understanding how the GLP-1 hormone, and the therapies derived from it, function in the body. His early discovery that GLP-1 stimulates insulin secretion in a glucose-dependent manner paved the way for today's widely popular medications for type 2 diabetes and obesity. Dr. Drucker's ongoing research continues to shine light on the less understood aspects of GLP-1 biology including its effects on the liver and in regulating inflammation. [Colin Dewar, Sinai Health]](https://www.genengnews.com/wp-content/uploads/2026/04/Low-Res_Drucker_LTRI_Colin_Dewar-225x300.jpeg)
LSECs line the tiniest blood vessels in the liver and are studded with pores that allow them to act as a molecular sieve, filtering substances passing between the liver and the bloodstream. Gonzalez-Rellan showed that semaglutide reversed MASH in mice that lacked the brain receptors controlling appetite, demonstrating that weight loss is not required for liver benefits. “Unexpectedly. semaglutide improves hepatic inflammation, fibrosis, and immune remodeling through actions on Glp1r+ pericentral liver sinusoidal ECs (LSECs) independent of changes in body weight (BW),” the team reported. “… we leveraged a unique model of GLP-1R deficiency, Glp1rWnt1-/- mice, which are resistant to GLP-1RA-induced weight loss. Remarkably, semaglutide markedly improved hepatic steatosis, fibrosis, and immune remodeling in the absence of weight reduction.”
In a further test, mice lacking LSEC receptors showed no liver improvement on semaglutide even after losing 20% of their body weight. Detailed molecular analyses of liver cell types showed that semaglutide shifts gene activity in LSCEs, prompting them to release anti-inflammatory molecules that act on the broader liver environment, pushing it toward a state more closely resembling a healthy, disease-free liver. “Together, the data using mouse models of MASH reveal an EC-specific, weight-loss-independent, semaglutide-regulated, GLP-1R-dependent intrahepatic network for improving liver health,” the scientists said.
“It turns out that the receptor responsible for these benefits is in a very specialized population of liver cells,” commented Drucker, who is also a professor of medicine at the University of Toronto. “And this receptor orchestrates the production of molecules that talk to many different types of liver cells to calm down the inflammatory environment that is the problem in metabolic disease.”
The findings carry practical implications. GLP-1 medicines have become widely prescribed, yet their mechanism of action in the body, beyond appetite suppression and blood sugar control, have remained incompletely understood. Knowing that semaglutide improves liver health independently of weight loss could influence prescribing decisions. “We’ve seen in clinical trials that patients who lose very little weight see the same reductions in liver inflammation, scarring and enzyme levels as those who lose a great deal of weight. Now we know why,” Drucker pointed out. In their paper the team concluded “Hence, semaglutide produces a broad proteomic remodeling of the liver, enabling restoration of metabolic homeostasis and suppression of fibrogenic and inflammatory programs. The strong concordance between single-cell transcriptional changes, bulk tissue proteomics, and biomarker signatures underscores the breadth of GLP-1R-mediated hepatic reprogramming.”
Physicians may choose lower doses that avoid the side effects associated with the higher doses needed for significant weight loss, potentially also lowering costs for patients, Drucker suggested adding “We’re not saying weight loss isn’t important because many things improve when patients lose weight. But we now know that weight shouldn’t be the only measure of success, because GLP-1 medicines will improve liver health whether or not the patient loses weight.”
The post GLP-1 Drug Improves Liver Health Independent of Weight Loss, Mouse Study Finds appeared first on GEN – Genetic Engineering and Biotechnology News.
Cancer researchers in the United States are once again bracing for a high-stakes funding battle in Washington, as a proposed $6 billion cut to the National Institutes of Health (NIH) for fiscal year 2027 threatens to derail years of scientific progress.
For advocates like Jon Retzlaff, Chief Policy Officer and Vice President for Science Policy and Government Affairs at the American Association for Cancer Research (AACR), the situation feels strikingly familiar and deeply consequential. That sense of déjà vu is shaping the response from the cancer research community, which is now urging Congress to once again reject the administration’s proposal just as it did last year.
To understand the urgency of the current moment, Retzlaff points back to the turmoil of the previous budget cycle. “A year ago, the president had proposed a 40% cut to NIH,” Retzlaff told Inside Precision Medicine. “Things looked pretty bleak.” The consequences were immediate and unsettling: grants were stuck and there were cutbacks on committees and staff.
But Congress ultimately intervened decisively. “We engaged with Congress, who has the power of the purse,” Retzlaff said. “They summarily rejected the president’s proposal for the 40% cuts and instead provided a $450 million increase for NIH.” Lawmakers also delivered a significant boost to the National Cancer Institute (NCI), reinforcing what Retzlaff described as a clear signal of bipartisan support for biomedical research. “What we saw for the current fiscal year… is they summarily rejected the president’s proposal,” Retzlaff said. “So now we are going through the exercise all over again.”
Despite the renewed threat, Retzlaff sees reasons for hope rooted in last year’s outcome. “People asked, ‘How can you be so optimistic?’” He recalled the earlier funding fight. “At least this year, I’m going to be able to tell them why I can be optimistic,” he said. “Because it was Congress that stood up.”
Still, he cautioned against complacency. “We can’t rest on our laurels. We can’t take it for granted,” Retzlaff said. “We will be continuing to press the issue.”
For AACR, the renewed funding fight underscores a central truth: cancer research depends on long-term, uninterrupted investment. “You need this sustained funding over time,” Retzlaff said. “You go where the science is showing opportunities and also where there might not be opportunities right now.”
He emphasized that scientific progress is rarely linear or predictable. “Even though people can’t necessarily say it’s clear-cut that if we do research in this, we’re going to make some progress,” he said, “for some of the cancers, we just need to do research to try to have that knowledge discovery going on.”
Retzlaff added, “Basic biology is so important,” stressing that foundational science underpins every future breakthrough and the continued growth of precision medicine as the new standard of healthcare. “It’s about identifying the biomarkers that are important,” Retzlaff explained.
Meanwhile, emerging areas such as cancer vaccines are generating both excitement and urgency. “Cancer vaccines are now a big issue,” he said. “AACR is very interested in pushing that kind of research forward.”
Yet all of this progress depends on stable funding. Without it, Retzlaff warned, research priorities could narrow dangerously. “If you start cutting back, the next thing you know, we’re just funding breast cancer and lung cancer,” he said, “whereas the rare cancers need to be investigated. We need to give those people hope.”
Funding cuts would also ripple through the clinical research pipeline. Retzlaff, who has become more involved in clinical trials in recent years, noted their complexity and cost.
While pharmaceutical companies often support later-stage development, early and exploratory studies depend heavily on NIH funding. “We rely on pharmaceutical companies… once you get into the translational part,” he explained, but without federal investment at the front end, fewer discoveries will ever reach that stage.
For AACR, protecting NIH funding is about more than preserving scientific momentum; it’s about sustaining a national commitment to health. “We’ve got 50,000 members,” Retzlaff said. “Two-thirds of them are from the U.S., and probably two-thirds of them are completely reliant in many ways on NIH funding.” That dependence drives the organization’s advocacy efforts. “Our number one priority is inspiring excitement on Capitol Hill and from lawmakers for robust, sustained and predictable funding for the NIH,” he said.
AACR’s outreach spans everything from congressional briefings to large-scale advocacy events. “It’s working with the entire community,” Retzlaff said, noting collaborations with hundreds of organizations and initiatives, such as Medical Research Hill Day. “We’re constantly looking at drum[ming] up conversations with the media,” he added. “It’s things like that—briefings, reports, letters—you name it.”
At the same time, AACR is navigating broader policy and public health challenges. Retzlaff highlighted ongoing engagement with the Food and Drug Administration (FDA) on issues ranging from clinical trial efficiency to tobacco regulation.
Prevention, too, remains a critical priority. “HPV prevention is very important,” he said, though he acknowledged that misinformation has slowed progress. “The anti-vaccine movement is a huge concern.”
Retzlaff said that the cancer vaccine issue is rooted in communication and not the regulators. According to Retzlaff, the director of the National Cancer Institute has had some meetings with Secretary Kennedy, who was supportive of moving cancer vaccines forward. “We have to figure out what it is that people will accept about cancer vaccines that they’re not accepting about vaccines overall,” Retzlaff said. “That’s a communication issue… trying to combat the misinformation out there.”
AACR has even debated trying new names for the modality. Retzlaff elaborated, “There was some discussion about whether we can change the name of this from ‘cancer vaccines’ to something else.”
As Congress weighs the proposed cuts, AACR is calling on researchers, patients, and advocates to speak out once again. The message, Retzlaff said, is simple but urgent: “We definitely want to get the information out… about the importance of NIH medical research… and inspire people to take action.”
The outcome will determine not only the trajectory of cancer research but also the pace at which new discoveries can translate into treatments and, ultimately, save lives.
The post AACR Warns Congress of Cancer Care Setbacks from Proposed NIH Cuts, Again appeared first on Inside Precision Medicine.
While developing an ultrasensitive test for the detection of Mycobacterium tuberculosis DNA (TB-DNA), researchers from Boston University have unexpectedly found a high prevalence of the molecular marker in U.S.-born patients hospitalized in Boston.
“We began this research with the intent of sourcing respiratory samples to support the ongoing development of a new molecular assay for TB,” said Guillermo Madico, MD, PhD, scientist at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and co-inventor of the TOP TB assay. “What we found was completely unexpected. Our ultrasensitive test is detecting Mycobacterium tuberculosis DNA in patients who are unlikely to be diagnosed with TB using current methods. This opens the possibility that there could be thousands of Americans infected with forms of tuberculosis disease that remain hidden from our current diagnostic tools—putting them at risk of developing more serious complications or potentially transmitting the disease to others.”
In 2022, there were over 8000 reported cases of TB in the United States, over 600 TB-related deaths, and an estimated 13 million people with Mycobacterium tuberculosis infection. Although incidence has steadily decreased in the U.S., the rate of decline is too slow to meet the ambitious World Health Organization strategy to end the global TB epidemic by 2035.
One threat to the global elimination goal is a gap in the detection of paucibacillary TB disease—a type of TB characterized by a low concentration of M. tuberculosis bacilli in samples that often results in false negative test results.
To improve detection, Madico and colleagues developed an ultrasensitive molecular assay developed at Boston University called the Totally Optimized PCR (TOP) TB assay, which targets a gene involved in M. tuberculosis cell wall assembly.
During the development process, the researchers conducted three separate clinical studies involving 297 patients from Boston hospitals.
Across the studies, the TOP TB assay detected TB DNA in 12–16% of samples—a rate far higher than expected given Boston’s low TB incidence rate. Of note, most TB DNA-positive patients tested negative on standard TB infection tests (tuberculin skin tests or interferon-gamma release assays), and the researchers hypothesize that the findings “indicate the existence of a paucibacillary form of TB that remains unrecognized and is not detectable using current diagnostic tools.”
During the study, there were three patients diagnosed with acute chest syndrome, a life-threatening complication of sickle cell disease, all of whom tested positive for TB DNA.
The researchers point out in Nature Communications that this “previously unrecognized association” has potential implications for clinical care in the U.S. and many other settings.
“These findings suggest we may be missing a significant burden of TB disease, particularly in older Americans and in patients with certain underlying conditions,” said Edward Jones-López, MD, who co-led the study while at Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine. “Most concerning is the potential association with acute chest syndrome in sickle cell patients. If confirmed and expanded upon in larger studies, this finding could lead to better health outcomes for patients with this potentially life-threatening condition.”
The researchers emphasize that their preliminary findings require confirmation in larger, prospective multicenter studies that include comprehensive clinical, radiological, immunological, and microbiological correlation. However, they argue the evidence warrants immediate dissemination given potential implications for medical care and public health.
The post Ultrasensitive Molecular Test Identifies Substantial TB Underdiagnosis in Boston appeared first on Inside Precision Medicine.
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Trump deleted an AI image of himself on Truth Social looking a whole lot like Jesus after conservative Christians cried blasphemy. “It’s supposed to be me as a doctor,” Trump told reporters while stepping out of the Oval Office to get a McDonald’s delivery. Send news tips and surprising health care angles to John.Wilkerson@statnews.com or John_Wilkerson.07 on Signal.
Congress returns to a packed health care agenda after two weeks off. Here’s what to follow.
Gene editing has been able to silence the extra chromosome that is mostly responsible for Down syndrome (DS) in a cell-based study that could be the first step towards therapeutic treatment.
The approach uses a modified form of CRISPR-Cas9 to alter precise sections of DNA.
Researchers used this to insert the X-inactivation specific transcript (XIST) gene to deactivate X chromosomes in female cells, thereby correcting chromosomal triplication.
The partial transcriptional correction, reported in PNAS, offers a scalable, targeted platform for chromosomal therapy in Down syndrome and other aneuploidy disorders, which are conditions involving an abnormal number of chromosomes.
“These studies overcome a major hurdle in the treatment of Down syndrome (a genetic disorder cause by three rather than two copies of chromosome 21) by dramatically increasing the efficiency with which to insert XIST onto a single copy of chromosome 21 and thereby silencing this third copy,” senior researcher Volney Sheen, PhD, from Beth Israel Deaconess Medical Center, told Inside Precision Medicine.
“Determination of the best ways and times to deliver these constructs to the brain will become the next focus as we seek a clinical treatment for DS.”
Down syndrome is the most common genetic disorder and occurs in one out of 700 live births. It is linked with cognitive impairment, heart defects, and early-onset Alzheimer’s disease and results from the triplication of approximately 500 genes as well as other genetic changes on chromosome 21.
The XIST gene produces a long, noncoding RNA that inactivates many of the genes on one of the two X chromosomes of female mammals. It has therefore been mooted as a treatment for Down syndrome but technical limitations, including low levels of gene integration, have hindered progress.
In an attempt to address this, Sheen and team created a CRISPR-based method that involved fusing a codon-optimized λ-phage with Cas9, assembling single guide (sg)RNAs specific to single nucleotide polymorphisms (SNPs), and enhancing donor-acceptor DNA pairing.
The modified CRISPR-Cas9 method achieved a high level of genomic integration of large genetic material, improving the efficiency and specificity of XIST integration.
Inserting XIST onto one of the trisomic chromosome 21 alleles using SNP-dependent sgRNAs achieved an integration efficiency of 20% to 40% for the 14kb XIST gene.
XIST integration was revealed through expression of the enhanced green fluorescent protein reporter, clonal sequencing of individual lines, and fluorescent in situ hybridization.
The team further demonstrated that XIST activation led to upregulation of epigenetic markers, broad downregulation of messenger RNA expression on chromosome 21, and downregulation of specific genes on this chromosome.
“Our findings demonstrate atrial transcriptional correction of trisomic gene dosage and offer a scalable targeted platform for chromosomal therapy in DS and other aneuploidies,” the researchers reported.
They added: “The modified CRISPR method with XIST paves a rode for therapeutic treatment for DS.”
The post Down Syndrome Chromosomal Therapy Draws Closer appeared first on Inside Precision Medicine.