Reduce bad cholesterol by 59%! Gene therapy successfully lowers fat in primates for the first time

"Lucky" born with low blood lipidscoronary artery disease, also known as coronary heart disease, is the most common type of heart diseaseIt is due to the deposition of cholesterol in the blood vessels, causing the arterial blood vessels to narrow, or even completely blocked, eventually leading to a heart attackAccording to the World Health Organization, coronary heart disease kills 7.3 million people worldwide each year, and its prevalence is increasingWhile there are many treatments available to help control cholesterol levels, including common statins, the long-term risk of coronary heart disease means that patients may need to take the drug for more than a decade, or even decades, and compliance is one of the most important barriers to cholesterol levelsStudies have shown that only 39 percent of patients who have had a heart attack are able to follow a doctor's order and take statins for long periods of timehowever, there are a small group of "lucky people" who are genetically born with mutations that significantly reduce their risk of coronary heart diseaseA 2006 paper published in the New England Journal of Medicine found that people who carried a inactive PCSK9 gene had an 88 percent lower lifetime risk of coronary heart disease than those who carried two normal PCSK9 genesIn a 2010 paper published in the New England Journal of Medicine, people who carried the inactive ANGPTL3 gene had a 34 percent lower lifetime risk of heart attack, is there any way to simulate these genetic mutations so that others can also become "lucky people" with a reduced risk of coronary heart disease?a variety of strategies targeting PCSK9
has been approved by the FDA for listing by targeting the PCSK9 protein, and The Praluent, developed by Amgen, has been approved by the FDABoth therapies are monoclonal antibodies that target the PCSK9 protein and can further lower cholesterol levels after the patient takes the maximum dose of statinsHowever, patients still need to be injected every 2-4 weeks, which is inconvenient for long-term treatmentso, The Medicines Company and Alnylam have developed an RNAi treatment that targets PCSK9, which can effectively control cholesterol levels by receiving only two injections a yearThe RNAi therapy, called inclisiran, is currently under FDA review and is expected to be the first RNAi therapy to treat a large number of patients with a wide range of patientsNovartis acquired The Medicines Company last year for nearly $10bn, the innovative treatment verve Therapeutics' research therapy goes a step further, with the company's idea of inactivating the PCSK9 gene in liver cells through CRISPR-based monobase editing technology, so that patients can permanently shut down the PCSK9 gene with just one treatment, making them the "lucky ones" to reduce the risk of coronary heart disease for life, as mentioned above single-base editing techniques to modify the genome's "pencil and rubber" From its inception, Verve Therapeutics partnered with Beam Therapeutics, a single-base editing company based on CRISPR systems Monobase editing still uses Cas9 proteins and guide RNA in crispR systems to find specific sequences in the genome, but unlike the average CRISPR-Cas9 gene editing system, the monobase editor does not cut off DNA after finding a specific sequence, but instead converts one of the base pairs into another base pair (e.g A-T to G-C) Professor David Liu, co-founder of Beam Therapeutics, once likened it to a "pencil and rubber" that modifies the genome, avoiding other mutations introduced by DNA fractures because dna does not need to break "once and for all" fat-lowering therapy? in the results, published over the weekend, researchers edited 14 crab-eating monkeys with monobases of liver cells in the body, targeting the PCSK9 gene, which causes elevated LDL cholesterol, or the ANGPTL3 gene, which causes elevated triglycerides The results showed that after two weeks of treatment, 67% of pcSK9 genes in the liver of animals that received PCSK9 monobase editing were successfully edited, resulting in an 89% decrease in PCSK9 protein levels in plasma and a 59% decrease in LDL cholesterol levels and ANGPTL3 monobase editing led to 60% of ANGPTL3 in the liver being successfully edited, with ANGPTL3 levels reduced by 95%, triglycerides by 64%, and LDL cholesterol levels decreased by 19% also important, the researchers found no side effects associated with monobase editing in animals, and used protozoa human liver cells, and the researchers found no evidence of off-target editing Dr Sekar Kathiresan, co-founder and CEO of Verve, said that while there are only a few months of follow-up observations on these animals, he is confident about the durability of single-base editing Because monobase editing directly modifies the genome of a cell, inactivated genes are passed on to the next generation of cells as the cells divide, thus achieving a "once and for all" therapeutic effect The company now plans to develop this gene-editing therapy to treat patients with familial hypercholesterolemia, but Dr Kathiresan's vision is to "change the way cardiovascular disease is treated" and he hopes that in the future people will no longer need to take statins for decades, but will be able to be protected for life, as "lucky people" who are born with mutations in PCSK9 or ANGPTL3.