We cripple one, treat the other
Doctors have created a gene therapy that protects against atherosclerosis
American molecular biologists and physicians have developed a new type of gene therapy that dramatically reduces cholesterol and fat levels in the blood by damaging the ANGPTL3 (angiopoietin-like 3–VM) gene, according to an article published in the journal Circulation (Chadwick et al., Reduced Blood Lipid Levels With In Vivo CRISPR-Cas9 Base Editing of ANGPTL3).
"Such therapy will be especially useful for people suffering from familial hypercholesterolemia, a rare genetic disease, with the development of which the level of cholesterol in the blood becomes prohibitively high. It is almost impossible to treat it with medication. A single injection of CRISPR "vaccine", which will be ready in the next five years, will help to get rid of it forever," says Kiran Musunuru from the University of Pennsylvania in Philadelphia (in a press release, Gene-editing Reduces Triglycerides, Cholesterol by Up to 50 Percent, Finds Penn Animal Study – VM).
In recent years, scientists have made significant progress in creating various types of gene therapy that allows you to remove individual genes and DNA segments associated with the development of various hereditary diseases and replace them with "corrected" versions. For example, last year scientists created a therapy to combat retinal degeneration, and two years ago they managed to stop muscle degeneration in a mouse suffering from myodystrophy.
Musunuru and his colleagues used genetic engineering methods to combat the main killer of people in developed countries and countries with economies in transition – heart and vascular diseases associated with the accumulation of cholesterol plaques and other deposits on the walls of blood vessels.
According to current WHO statistics, approximately one in seven people in the United States and other first world countries die from coronary heart disease, heart attacks and other diseases caused by atherosclerosis. As scientists now suggest, the number of its victims will grow rapidly in the coming years due to the general aging of the world's population and the spread of sedentary lifestyle and malnutrition.
As Musunuru says, large-scale genetic studies in recent years show that there are relatively few people on Earth who practically do not suffer from such health problems due to mutations in one or two copies of the ANGPTL3 gene.
This DNA site not only controls the growth of blood vessels and the migration of their cells, but also suppresses the work of two enzymes that break down the "harmful" version of cholesterol and fat molecules, which is why its excessively high activity leads to their accumulation in the circulatory system. Accordingly, mutations in ANGPTL3 lead to the opposite – the body breaks down almost all the fat reserves in the blood, which protects their carriers from atherosclerosis.
Guided by this idea, scientists created a retrovirus based on a new CRISPR/Cas9 genomic editor that penetrates into mouse liver cells and damages ANGPTL3, and tested its work on ordinary mice and their relatives suffering from hypercholesterolemia.
The first changes in the work of the rodents' body appeared just two weeks after the introduction of the retrovirus – the level of cholesterol and fats in their blood decreased by 50-56%. Such changes affected both healthy mice and their relatives with congenital disease, which allowed them to reduce the concentration of fats in their blood to conditionally safe levels.
According to biologists, such impressive results were obtained with a fairly modest efficiency of the virus – it managed to penetrate only a third of liver cells. Increasing his "combat capability", according to Musunuru and his colleagues, will make such a "vaccination" against atherosclerosis even more effective.
In the near future, geneticists plan to conduct the first trials of a "human" version of this gene therapy using mice whose liver partially consists of human cells. If these experiments are completed successfully, then, according to Musunuru, it will be possible to think about the beginning of preclinical and clinical trials on volunteers.
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