Method of editing genes have successfully lowered cholesterol levels in macaques


Method of editing genes have successfully lowered cholesterol levels in macaquesResearchers from the University of Pennsylvania has reduced the level of cholesterol in monkeys by editing genes.

Using technology for editing genes to suppress expression of a particular gene, researchers at the University of Pennsylvania has lowered the level of cholesterol in the blood of rhesus monkeys. All they did was cut off the only gene in the liver. Successful experiments pave the way for future clinical trials in 5-10 years.

The aim of the study was a well-known protein called PCSK9. Previous scientific work has shown that PCSK9 inhibits the ability of the liver to get rid of bad cholesterol.

Several drugs have been developed to suppress the activity of the protein, but they are quite expensive and, more importantly, are not always effective.

Some scientists are studying the ways genetic inhibition (suppression) of PCSK9. And a recent study is the first that demonstrated the effective reduction of PCSK9 in the liver through editing of genes in macaques.

Instead of the more popular methods of editing CRISPR genes, experts used slightly older and a slightly different method called gene editing based on meganuclease (meganuclease-based gene-editing).

Identified in the 1990-ies meganuclease are enzymes that can be designed for precise editing of genes. In the recent experiment, the enzyme was designed for inactivation (reduction of activity) of the gene PCSK9. He was taken to the liver using AAV harmless virus (AAV).

The results were impressive: in the body of rhesus monkeys observed reduction in PCSK9 levels between 45 and 84 per cent, and the associated level of cholesterol was reduced to 60 percent. Analysis of liver tissue revealed actionable mutations in the 40-65 percent of the genes of PCSK9.

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Method of editing genes have successfully lowered cholesterol levels in macaques

Researchers from the University of Pennsylvania has reduced the level of cholesterol in monkeys by editing genes.

Using technology for editing genes to suppress expression of a particular gene, researchers at the University of Pennsylvania has lowered the level of cholesterol in the blood of rhesus monkeys. All they did was cut off the only gene in the liver. Successful experiments pave the way for future clinical trials in 5-10 years.

The aim of the study was a well-known protein called PCSK9. Previous scientific work has shown that PCSK9 inhibits the ability of the liver to get rid of bad cholesterol.

Several drugs have been developed to suppress the activity of the protein, but they are quite expensive and, more importantly, are not always effective.

Some scientists are studying the ways genetic inhibition (suppression) of PCSK9. And a recent study is the first that demonstrated the effective reduction of PCSK9 in the liver through editing of genes in macaques.

Instead of the more popular methods of editing CRISPR genes, experts used slightly older and a slightly different method called gene editing based on meganuclease (meganuclease-based gene-editing).

Identified in the 1990-ies meganuclease are enzymes that can be designed for precise editing of genes. In the recent experiment, the enzyme was designed for inactivation (reduction of activity) of the gene PCSK9. He was taken to the liver using AAV harmless virus (AAV).

The results were impressive: in the body of rhesus monkeys observed reduction in PCSK9 levels between 45 and 84 per cent, and the associated level of cholesterol was reduced to 60 percent. Analysis of liver tissue revealed actionable mutations in the 40-65 percent of the genes of PCSK9.

"Our initial work with multiple approaches to delivery and edit produced the most impressive data from non-human primates, when we combined the AAV for delivery designed by meganucleases to edit" says senior author James Wilson (James Wilson).

Several other research groups are also working on "disconnecting" the gene PCSK9, considering this approach a promising treatment of heart disease. Other experiments using the method for genome editing CRISPR has also been successful in trying "disable" PCSK9 in mice (we reported on this experiment).

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Meanwhile, a team of scientists from the University of Pennsylvania was able to successfully reproduce these results in primates, which, in fact, led to the use of another method of editing genes.

However, experiments are not without unwanted side effects. The researchers reported that the treatment leads to an increase of liver enzymes, which may indicate some degree of immune response to therapy.

Not to say that such an outcome was completely unexpected to scientists. Perhaps the course of treatment can lead to the development of a more enhanced immune response. We have also identified some so-called non-targeted genetic "interruptions" that can lead to the development of cancer.

Obviously too early to talk about the development and use of this method of treatment, and the researchers believe that it is necessary to obtain more results, before you start or even think about clinical trials.

One of the study’s authors Wang Lili (Lili Wang) believes that there are still about 5-10 years of research to test the method on humans.

"First and foremost we have to achieve many improvements, carefully assess and characterize this technology on models of large animals to provide both safety and efficiency"— says the scientist.

However, the team is confident that this approach can lead to promising treatment of patients suffering from life-threatening forms of cardiovascular disease.

Edit the gene for the cholesterol-lowering seems to be a promising method for treatment of cardiovascular diseases in the future. But, as noted by the authors, it is necessary to conduct more research to be sure for sure.

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A description of the method and results of the experiment are presented in the scientific journal Nature Biotechnology.

Previously, the authors of the project "News.Science" (nauka.vesti.ru) told me that edit DNA for the first time to help treat liver disease. Also you reported that the development of cardiovascular diseases influenced by intestinal bacteria.

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