Daily Archives: March 11, 2022

FRIDAY, March 11, 2022 (HealthDay News) -- A one-time infusion of betibeglogene autotemcel (beti-cel) gene therapy yields high levels of transfusion independence in children and adults with transfusion-dependent -thalassemia and a non-0/0 genotype, according to a study published in the Feb. 3 issue of the New England Journal of Medicine.

Franco Locatelli, M.D., Ph.D., from the University of Rome, and colleagues conducted an open-label phase 3 study to examine the efficacy and safety of beti-cel in adult and pediatric populations with transfusion-dependent -thalassemia and a non-0/0 genotype. Twenty-three patients were enrolled, underwent myeloablation with busulfan, and then received intravenous beti-cel. Patients were followed for a median of 29.5 months.

The researchers found that 20 of the 22 patients (91 percent) who could be evaluated had transfusion independence, including six of seven (86 percent) who were younger than 12 years. During transfusion independence, the average hemoglobin level was 11.7 g/dL. In patients with transfusion independence, the median level of gene therapy-derived adult hemoglobin with a T87Q amino acid substitution was 8.7 g/dL at 12 months after beti-cel infusion. Four patients had at least one adverse event considered to be related or possibly related to beti-cel; all except one were nonserious. There were no cases of cancer.

"These data suggest that in most patients with transfusion-dependent -thalassemia and a non-0/0 genotype, one-time infusion of beti-cel is potentially curative through transfusion independence and the attainment of near normal hemoglobin levels," the authors write.

Several authors disclosed financial ties to biopharmaceutical companies, including Bluebird Bio, which funded the study.

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Gene Therapy Potentially Curative for -Thalassemia - Consumer Health News | HealthDay - HealthDay News

Specific comorbidities and conditions have been associated with severe COVID-19, including diabetes, obesity, and, of course, older age. But researchers have now identified 16 new genetic variants associated with severe COVID-19. For that and more research stories, continue reading.

16 Genetic Variants Associated with Severe COVID-19

Investigators with theUniversity of Edinburghanalyzedthe genomes of 57,000 people, part of the GenOMICC consortium, a global collaboration to study genetics in critical diseases. They identified 16 new genetic variants associated with severe COVID-19 and sequenced the genomes of 7,491 patients from 224 intensive care units in the U.K. That DNA was compared with 48,400 other people who did not have COVID-19. They were participants inGenomics Englands 100,000 Genomes Project and another 1,630 people who had mild COVID-19. The findings are published inNature.

Our latest findings point to specific molecular targets in critical COVID-19, said Professor Kenneth Baillie, the projects chief investigator and a Consultant in Critical Care Medicine at the University of Edinburgh. These results explain why some people develop life-threatening COVID-19, while others get no symptoms at all. But more importantly, this gives us a deep understanding of the process of disease and is a big step forward in finding more effective treatments.

In addition to the 16 new gene variations, they confirmed seven other genetic variations that were already linked with severe COVID-19. Part of their findings was a single gene variant that can disrupt interferon alpha-10, a key messenger molecule in immune system signaling. This variant alone was enough to increase a patients severe disease risk. Another variation is Factor 8, which is important to blood clotting, and was connected to critical COVID-19.

Nanoparticle decreases Scleroderma Skin and Lung Scarring

Researchers withMichigan Medicine University of Michiganidentifieda unique macrophage, a type of immune cell, that plays a significant role in the chronic inflammation and scarring seen in the lungs and skin of scleroderma patients. The macrophage, dubbed MARCO+, was isolated in people with the disease, which is rare and affects about 70,000 people in the U.S. They then, working with laboratory mice, injected the animals with biodegradable PLG (lactic-co-glycolic acid) nanoparticles that targeted MARCO+ inflammatory cells. This appeared to prevent the skin and lung fibrosis in the mice associated with the disease. The team theorizes that the MARCO+ cells are activated in scleroderma, circulate in the bloodstream, move to tissues, and cause scar formation.

A Predictive Model for Rheumatoid Arthritis

Scientists fromTokyo Medical and Dental Universitydevelopeda genomic model to predict the progression of rheumatoid arthritis. They utilized data from a genome-wide association study (GWAS) of R.A. susceptibility. They then developed a polygenic risk score (PRS) and tested it to predict radiographic progression in people with rheumatoid arthritis. Earlier studies identified specific genetic factors for R.A. progression, including anti-citrullinated protein antibodies (ACPAs) and variants in the human leukocyte antigen (HLA) region of the chromosome that regulates the immune system. Those are useful but not considered robust. Their new analysis found that patients with a higher PRS had a higher risk of severe progression, particularly in people who were younger at the onset.

microRNAs Unique to Human Beings

Student researchers atJohn Jay College of Criminal Justiceidentifiedhuman microRNA genes that are not found in any other primate species. They believe they may have had a significant role in the evolution of human beings. They found at least three families of microRNA genes on chromosome 21. They leveraged genome alignment tools and compared the most recent versions of human and chimpanzee genomes, working to find genetic elements unique to humans.

On chromosome 21, they found a large region of unique DNA called 21p11, which harbors several orphan microRNA genes. The long arm of human chromosome 21 matches up well with other ape species, but the short arm aligns poorly. The microRNAs in that region, specifically miR3648 and miR6724, probably evolved since the chimpanzee and human lineages split probably in the last seven million years.

Organs Age at Different Rates

Youre only as old as you feel, right? Well, maybe. Butnew researchout of theBeijing Genomics InstituteandChina National GeneBankin Shenzhen, China, found that different organs and systems have different ages from a biological perspective.

Using biomarkers, statistical modeling, and other tools, they analyzed the aging in 4,066 volunteers who supplied blood and stool samples, facial skin images, and to undergo physical fitness examinations. They were between the ages of 20 and 45 years. They measured 403 features: 74 metabolomic features, 34 clinical biomarkers, 10 electroencephalography features, 16 facial skin features, and 210 gut microbiome features. They then classified them into nine categories, including cardiovascular-related, renal-related, liver-related, sex hormone, facial skin, nutrition and metabolism, immune system, physical fitness-related and gut microbiome features. They found that the biological ages of different organs and bodily systems had diverse correlations. They also examined single nucleotide polymorphisms (SNPs) and identified certain genetic changes associated with aging-related pathways.

FDA-Approved Drug Halts RAS-Based Tumor Growth

Researchers with theUniversity of California, San Franciscousedan FDA-approved drug to stop tumor growth in cancers driven by mutations in the RAS gene. RAS mutations are typically difficult to treat and make up about one in four cancer deaths. They found that cancer cells require a reactive form of iron called ferrous iron. They then modified an anticancer drug to work only on these iron-rich cells, allowing other cells to function normally. They focused their research on RAS-mutated pancreatic and gastrointestinal cancers. Cobimetinib and similar drugs are effective at blocking the excessive growth stimulated by RAS mutations and do the same thing in non-cancer tissue, which causes serious side effects that lead many patients to discontinue treatment. They modified cobimetinib to have a small molecule that senses ferrous iron, which essentially shuts cobimetinib off until it meets up with ferrous iron in the cancer cells.

By removing toxicity from the equation, youre talking not just about one new drug, but 10 new combinations that you can now think about exploring in the clinic, said Adam Renslo, a pharmaceutical chemist at UCSF and co-author of the study. That would be the home run for this approach.

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Research Roundup: Genetic Variants Associated with Severe COVID-19 and More - BioSpace

NEW YORK

U.S. regulators on Monday cleared the way for the sale of beef from gene-edited cattle in coming years after the Food and Drug Administration concluded the animals do not raise any safety concerns.

The cattle by Recombinetics are the third genetically altered animals given the green light for human consumption in the U.S., after salmon and pigs. Many other foods already are made with genetically modified ingredients from crops like soybeans and corn.

The cattle reviewed by the FDA had genes altered with a technology called CRISPR to have short, slick coats that let them more easily withstand hot weather. Cattle that arent stressed by heat might pack on weight more easily, making for more efficient meat production.

The company did not say when home cooks or restaurants might be able to buy the beef, but the FDA said it could reach the market in as early as two years.

Unlike the salmon and pigs, the cattle did not have to go through a years-long approval process. The FDA said the cattle were exempt from that because their genetic makeup is similar to that of other existing cattle and the trait can be found naturally in some breeds.

Dr. Steven Solomon, director of the FDAs Center for Veterinary Medicine, said the agencys review of Recombinetics cattle took several months. He said theres no reason that meat from the animals or their offspring would need to be labeled differently.

Solomon said a genetically altered animal marketed as having a special advantage such a higher than normal ability to withstand heat might need to go through the full approval process.

This opens up a completely different pathway, he said, noting the decision could be encouraging for other biotech companies, many of which are small startups.

The gene-edited trait in the Recombinetics cattle can be passed down so semen and embryos from them could be used to produce offspring with the same shorter coats.

The trait will make beef production more sustainable and could improve animal welfare in warmer climates, Recombinetics said in a statement without providing further details.

Greg Jaffe, who specializes in biotechnology at the Center for Science in the Public Interest, said the FDAs announcement made clear it wasnt exempting all gene-edited animals from the longer approval process.

They reinforce the idea that this is a case-by-case review, Jaffe said.

He said the agency should be more transparent about the review process so people know whats in the works. That could lead to better public acceptance and minimize any potential economic disruptions from global trade, since other countries might consider the animals genetically modified foods that need to be labeled, he said.

Jaydee Hanson, of the Center for Food Safety, said the agency should keep track of the animals for several generations to ensure there arent any unintended issues.

The genetically modified pig is intended mainly for medical purposes, not meat, according to the company that developed it. The firm recently provided a pig heart that was transplanted into a dying man in an experimental surgery.

The company behind the modified salmon said the fish are being sold to distributors in the Midwest and Northeast.

Alison Van Eenennaam, an animal geneticist at UC Davis who has worked with Recombinetics, said requiring all companies to go through the lengthy approval process could end the possibility of commercializing gene-edited animals in the U.S.

For the gene-edited cattle cleared by the FDA, she said it could take about two years for beef from the offspring to reach the market.

Once the semen is used to create embryos, she said gestation would take about nine months and the resulting calves might be slaughtered after about 10 months. She noted the market isnt limited to the U.S., given the way cattle are bred.

Lets face it, bull semen goes all over the world, she said.

Continued here:
Gene-edited beef cattle receive regulatory clearance in U.S. - Los Angeles Times

Image of the female mouse that gave birth via asexual reproduction.PNAS

Chinese scientists have managed to get a female mouse to produce live viable offspring from an unfertilized egg thanks to gene editing. This is in theory the first case of a mammal that has achieved asexual reproduction, technically known as parthenogenesis or virgin creation, which is common in many insects and reptiles, and even in some bird species. But until very recently, it was believed that mammals could not reproduce without male genetic material.

In 2004, the world learned about Kaguya, a mouse born without the need for sperm or sexual reproduction. Mammals have two copies of each gene in their genome one from their mother and one from their father. When a sperm cell penetrates an egg, something called genomic imprinting happens, meaning that some genes behave differently depending on whether they were inherited from the father or the mother.

Many of the genes involved in the process have to do with growth, which may mean, for evolutionary reasons, that the fathers imprint favors growth in order to have larger offspring, while the mothers may do the opposite to ensure that the pregnancy can be brought to term. Some of these genes are also associated with a greater risk of suffering cancer, among other diseases. The Japanese scientists who created Kaguya used two eggs: one worked as the real egg while the other one imitated the sperms contribution. The result was a baby that was born to two females.

The new study, led by Yanchang Wei, a reproductive medicine researcher at Ren Ji Hospital in Shanghai, took the concept a step further, creating a pregnancy from a single, unfertilized egg. Chinese scientists used a gene-editing technique very similar to CRISPR, which is used in medicine and biotechnology. The authors of the study used the tool to imitate the genomic imprint in seven different points of the genome of an egg that already had two copies of each gene. This triggered a biochemical process that was the equivalent of fertilization: the egg grew from one single cell to a 140-cell blastocyst.

Theyve managed something fascinating but terribly inefficient

The scientists implanted 192 embryos made with this technique in as many female mice, but only one of them gave birth to a healthy pup that survived, although it weighed less than average. Two others died shortly after birth. The survivor reached adulthood and was able to reproduce normally.

In their study, published in the scientific journal PNAS, researchers noted that parthenogenesis can be achieved by targeted epigenetic rewriting of multiple critical imprinting control regions. The team believes that the technique could be perfected to achieve a higher live birth success rate. The success of parthenogenesis in mammals opens many opportunities in agriculture, research, and medicine, says the study.

It is a groundbreaking study, agrees Lluis Montoliu, a researcher at Spains National Research Council (CSIC), who underscored that the eggs had a copy of their genes and another copy taken from another egg that came from a different species of mouse, allowing scientists to check the effects of the editing. In theory at least, further perfecting this technique might allow a woman to have children on her own, admits Montoliu. But the researcher adds that its use on humans is a very long way off. The main thing now is to follow the lives of these mice born through these techniques, and see whether they have problems with their lives and reproduction. There are still a lot of unanswered questions.

Theyve managed something fascinating but terribly inefficient, adds David Haig, a researcher at Harvard University who developed a theory about genomic imprinting several years ago.

English version by Susana Urra.

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Female mouse gives birth without sex or sperm - EL PAS in English