Using CRISPR for the first time it was possible to conduct gene therapy in an adult mammal

Genetics from Duke University (USA) announced that for the first time in history they were able to successfully conduct gene therapy of an adult mammal (mouse) and cure it of a genetic disease associated with muscle dystrophy. For this, a modified version of the relatively new CRISPR / Cas9 gene editing technology was used. CRISPR / Cas9

gene editing technology involves the use of an adeno-associated virus that helps deliver genetic material to its destination. Using this technology, successful experiments were carried out on editing the genes of individual cells in test tubes and unicellular embryos.

Unfortunately, so far the possibility of genetic manipulation on human embryos causes fierce debate. Therefore, even if it is known in advance that the future person will be prone to certain genetic defects, you cannot help him in this way.

Common genetic diseases include Duchenne muscular dystrophy (named after the French scientist who first described it). It affects about 1 person out of 4-5 thousand, and usually males. The defect leads to insufficient production of dystrophin protein , which leads to muscle underdevelopment.

The dystrophin protein is encoded by a gene consisting of 79 exons (coding fragments of a DNA molecule). If one of the exons undergoes a mutation, the chain cannot be built.

Symptoms usually appear in children under 5 years old. The first signs of the disease are progressive proximal muscle weakness in the legs and pelvis, associated with loss of muscle mass. Gradually, this weakness spreads to the arms, neck and other parts of the body. To help with walking, at the age of 10 years, it may be necessary to use special braces, but most patients older than 12 years old cannot move without a wheelchair. Usually such people do not live more than 20-30 years.

Due to the lack of the ability to edit the genome at the embryo stage, scientists are looking for ways to genetic intervention in already developed organisms. In this regard, the problem of the delivery of genetic material to specific tissues of the body. Duke University has been trying to solve this problem of genetics since 2009.

“The recent discussion of the use of CRISPR technology to correct unwanted genetic mutations in human embryos is a matter of clear concern,” explains S. Gersbach, associate professor at the university and one of the authors. - But genetic methods to help patients suffering from the disease do not raise any questions. These studies have shown us a possible way to solve this problem, although much remains to be done. ”

A popular way to deliver genetic material is to use a specially prepared adeno-associated virus from which all harmful materials have been removed and what needs to be delivered to the cells has been introduced.

The problem, however, is that, compared to the AA virus, the CRISPR structure is quite large and difficult to pack inside the virus. CRISPR / Cas9 technology originates from the immune system of bacteria, and genetics, carefully studying various bacteria, have discovered a more compact version of the Cas9 protein.

By packing it into an AA virus, geneticists programmed the protein to remove the mutated exon from the chain. After that, the body’s immune system independently “cross-links” the chain, which turns out to be a little shorter, but at the same time it no longer has defects in its composition.

First, the geneticists were able to successfully cure the muscles on the paws of mice, and then, by injecting CRISPR / AAV into the blood of mice, improve the condition of all the muscles of the body, including the heart. This is a reassuring result, since people with Duchenne muscular dystrophy syndrome usually have heart muscle failure.