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Category: genetics

In addition to having access to large colonies of monkeys and other species, animal researchers in China face less public scrutiny than counterparts in the United States and Europe. Ji, who says his primate facility follows international ethical standards for animal care and use, notes that the Chinese public has long supported monkey research to help human health. “Our religion or our culture is different from that of the Western world,” he says. Yet he also recognizes that opinions in China are evolving. Before long, he says, “We’ll have the same situation as the Western world, and people will start to argue about why we’re using a monkey to do an experiment because the monkey is too smart, like human beings.”

This story, one in a series, was supported by the Pulitzer Center.

BEIJING, GUANGZHOU, JIANGMEN, KUNMING, AND SHANGHAI—Early one February morning, researchers harvest six eggs from a female rhesus macaque—one of 4000 monkeys chirping and clucking in a massive outdoor complex of metal cages here at the Yunnan Key Laboratory of Primate Biomedical Research. On today’s agenda at the busy facility, outside Kunming in southwest China: making monkey embryos with a gene mutated so that when the animals are born 5 months later, they will age unusually fast. The researchers first move the eggs to a laboratory bathed in red light to protect the fragile cells. Using high-powered microscopes, they examine the freshly gathered eggs and prepare to inject a single rhesus sperm into each one. If all goes well, the team will introduce the genome editor CRISPR before the resulting embryo begins to grow—early enough for the mutation for aging to show up in all cells of any offspring.

But as often happens when eggs are retrieved, all does not go well. Only one egg in this morning’s batch is mature enough to fertilize. “We were a little unlucky today,” says Niu Yuyu, who with facility director Ji Weizhi runs the gene-editing research. The group can afford a little bad luck, though. Through a combination of patience, ingenuity, and enormous animal resources, the team has already used CRISPR to create an astonishing range of genome-edited monkeys to serve as models for studying human diseases.

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Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene. The 3272–26AG and 3849+10kbCT CFTR mutations alter the correct splicing of the CFTR gene, generating new acceptor and donor splice sites respectively. Here we develop a genome editing approach to permanently correct these genetic defects, using a single crRNA and the Acidaminococcus sp. BV3L6, AsCas12a. This genetic repair strategy is highly precise, showing very strong discrimination between the wild-type and mutant sequence and a complete absence of detectable off-targets. The efficacy of this gene correction strategy is verified in intestinal organoids and airway epithelial cells derived from CF patients carrying the 3272–26AG or 3849+10kbCT mutations, showing efficient repair and complete functional recovery of the CFTR channel. These results demonstrate that allele-specific genome editing with AsCas12a can correct aberrant CFTR splicing mutations, paving the way for a permanent splicing correction in genetic diseases.

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ABOVE: © ISTOCK.COM, CYNOCLUB

Genetics hold far more sway over the mouse microbiome than transient environmental exposures, researchers reported July 26 in Applied and Environmental Microbiology. The results appear to contradict previous studies in humans that have found environmental factors to be more influential than genetics, and they add to an ongoing dialogue in the microbiome research community over how much control we hold over the bacterial communities in our guts.

Hila Korach-Rechtman, a microbiologist at the Israel Institute of Technology in Haifa, set out to identify the microbes in mice that become a fixture in the gut after being introduced through the environment. “We really wanted to find these bacteria that can be transferred and remain in the host, even though they have different genetics,” she says.

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Genetically Modified Bacteriophages Appear To Fight Off Resistant Bacteria : Shots — Health News Treatment with genetically altered bacteriophages — viruses that attack bacteria — may have halted a patient’s near-fatal infection, hinting at new ways to fight antibiotic-resistant bacteria.

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The trial is just one of a few underway to test the powerful CRISPR technology around the world. One of the most promising, for example, is studying whether gene editing can treat, and effectively cure, blood disorders such as beta thalassemia and sickle cell anemia.

In beta thalassemia, the hemoglobin part of red blood cells, which is supposed to pick up oxygen from the lungs and distribute it to the cells in the rest of the body, doesn’t work properly. Patients need to be transfused with donors blood regularly, and even with these transfusions, complications can occur if the dose isn’t right and iron levels in the blood cells spike, which can lead to organ damage and even death. In sickle cell disease, a mutation in the gene that makes hemoglobin causes the red blood cells to collapse into a sickle shape, which makes it more difficult for the cells to flow smoothly through the body’s arteries and veins. Blockages caused by the misshapen blood cells can lead to severe pain and strokes.

The biotech company CRISPR Therapeutics, founded by one of the technology’s co-developers, has engineered a solution to treat both conditions that relies on genetic modifications connected to the production of fetal hemoglobin. Normally fetal hemoglobin, which provides the developing fetus with oxygen via the blood while in utero, is shut off about six months after birth, and genes for adult hemoglobin are turned on. While it’s not clear why adult hemoglobin replaces the fetal version, researchers say that they have not seen any significant differences between the two types when it comes to the ability to transport oxygen to the body’s cells. However, since the genes for adult hemoglobin don’t produce healthy red blood cells in people with beta thalassemia and sickle cell disease, one treatment strategy is to introduce genetic changes that turn on fetal hemoglobin again.

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Today, we want to draw attention to a new study that shows how partial cellular reprogramming was able to reverse cellular aging and address age- and injury-induced blindness in mice.

Epigenetic alterations

One of the proposed reasons we age is the changes to gene expression that our cells experience as we get older; these are known as epigenetic alterations. These alterations cause harmful changes to cellular function and gradually shift our cells from a youthful to aged state.

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Two known gene mutations induce pathways that enhance pancreatic cancer’s ability to invade tissues and evade the immune system. Researchers report the molecular details of this process, providing insights into druggable targets for immunotherapies.

Mutations in the genes KRAS and TP53 are closely linked to pancreatic ductal adenocarcinoma, by far the most common type of pancreatic cancer. Pancreatic cancers are often already malignant when diagnosed, making its five-year survival rate extremely low—less than ten percent. So, understanding how it evolves at the molecular level could help anti-cancer drug development.

Hisataka Sabe of Hokkaido University and colleagues in Japan conducted tests in human cancer cells and in mouse models of the disease to investigate the roles of KRAS and TP53 gene mutations in pancreatic ductal adenocarcinoma. The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).

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