"Zinc fingers" will correct diseased genes

The first in vivo editing of the human genome will be carried out in a new clinical study

Marina Astvatsaturyan, Echo of Moscow

The California biotech company Sangamo Therapeutics announced its intention to use the "zinc fingers" method – a specially designed protein structure that is able to cut DNA with the help of a nuclease enzyme to introduce the gene of the missing blood clotting factor to male subjects with hemophilia B.

Experimental editing of the human genome has been carried out before, but cells outside the body have always been modified. For example, the cells of the immune system, T-lymphocytes from blood samples of HIV-infected people, were changed in such a way that they lost the ability to connect with the virus, as a result of which, after their return to the bloodstream, the spread of infection stopped in the patient.

Now Sangamo Therapeutics is recruiting volunteers for a clinical trial in which patients not only with hemophilia B, but also with Gurler and Hunter syndromes, will receive genes encoding enzymes that they lack, thanks to insertion into a precisely cut place on DNA with a zinc finger.

"For the first time, a new gene will be delivered directly to the liver," Sandy Macrae, the company's executive director, is quoted as saying by The Scientist. "These clinical trials are a big responsibility," he added.

Hemophilia B, to which part of the efforts of Sangamo's gene engineers are directed, is a severe blood clotting disorder caused by the absence of the F9 gene, the product of which, factor IX, is an enzyme involved in clotting. In two other clinical trials, people with Gurler and Hunter syndromes will be injected with two different genes encoding enzymes necessary for the breakdown of complex carbohydrates that are involved in the development of the body, the formation of blood vessels and so on. Without these enzymes, specific polysaccharides glycosaminglycans accumulate in cells, which causes various neurological conditions and cardiovascular diseases. 

In all three studies, zinc finger nucleases will cut a certain place in the albumin gene in hepatocyte liver cells, and the functional copy of the "correct" gene introduced with them will be embedded in this place as a result of the natural recombination process. The genetically engineered design will enter the body as a result of intravenous injection.

The incorporation of the introduced genes into the albumin gene is justified by the fact that this gene works especially actively in the liver, and the insertion of a new gene under its regulatory site gives hope for a high level of production of missing enzymes in patients, for example, factor IX in the case of hemophilia.

Portal "Eternal youth" http://vechnayamolodost.ru  23.05.2017