HIV gene therapy is at least safe
In these tests, the safety and durability of the biochemical effects of its use were confirmed.
Sum of technologiesThe new technique uses a number of advanced discoveries and developments in biochemistry, biology and medicine: the use of stem cells and their genetic modification, gene therapy, the use of RNA with enzymatic activity and the phenomenon of RNA interference, etc.
This technique consists in transplanting the patient's own blood stem cells (pluripotent hematopoietic cells), whose DNA includes three therapeutic genes that protect cells from HIV. A "relative" of HIV from the genus of lentiviruses, which does not cause diseases in humans, was used as a vector for gene delivery.
The action of all three genes is realized due to the RNAs synthesized on their matrix, which block the key reactions of the vital activity of the virus.
One of these genes encodes an RNA with enzymatic activity (ribozyme) that prevents the virus from interacting with the CCR5 receptor on the surface of immune cells. HIV uses this receptor to enter the cell. In large-scale studies, it has been shown that suppression of CCR5 synthesis reduces the level of replication (reproduction) of the virus, and this decrease can reach up to 90 percent.
Approximately three percent of Europeans are carriers of the CCR5 point mutation (CCR5-delta32), which prevents its interaction with the virus. Such people are not susceptible to HIV. In 2008, specialists from the Berlin Charite Clinic reported on the success of the treatment of a patient who developed leukemia due to HIV infection, requiring a bone marrow transplant. German doctors deliberately selected a donor with the CCR5 mutation for him, and 20 months after treatment they were unable to detect the virus in any of the patient's biological samples.
However, CCR5 is used to enter the cell by only one type of HIV – M-tropic. Another variety, T-tropic, interacts with the CXCR4 receptor for these purposes. Therefore, scientists decided to use two more genes with other mechanisms of action.
The first of them encodes an RNA "trap" that blocks the TAR - secondary structure in the viral genome necessary for HIV reproduction. The product of the third gene is a small RNA, which by RNA interference disrupts the work of the viral genes tat and rev, regulating the synthesis of TAR. Thus, these two genes act on different parts of the same process, enhancing each other's effect and preventing virus replication.
Immune cells derived from modified stem cells will contain therapeutic genes, which, in theory, will provide these cells with protection against HIV.
What could you doDuring the tests of the technique, genetically engineered stem cells were injected into four patients who were admitted for treatment of a complicated
AIDS lymphoma (oncological disease of lymphatic tissue characterized by an increase in lymph nodes and /or damage to various internal organs in which uncontrolled accumulation of "tumor" lymphocytes occurs). One of the most effective methods of treating this disease is to transplant the patient's own hematopoietic cells taken before the development of cancer.
The introduction of cells containing therapeutic genes to volunteers instead of the usual ones would make it possible to assess both the tolerability of treatment and its effectiveness. However, for ethical reasons, at the first stage of research, patients were injected with unchanged stem cells with only a small admixture of experimental ones.
Observation of volunteers for two years after treatment showed good tolerability of the new technique, as well as the absence of harm from the use of the lentiviral vector. In addition, during this entire period, genetically modified cells stably gave rise to blood cells, and a small (due to the small number of such cells), but continuous production of RNA encoded in therapeutic genes was observed.
The small number of "offspring" of genetically engineered cells and, as a result, the low concentration of antiviral RNAs did not allow to rid patients of HIV and even significantly reduce the viral load. Thus, the effectiveness of the new technique will be evaluated only in future studies, when only cells with additional genes will be injected into patients.
Even with the success of these studies, their duration, combined with the high-tech and high cost of the technique, will not allow this method of treatment to be used en masse for a long time. However, the first success confirming the expediency of work in this direction has been achieved.
Portal "Eternal youth" http://vechnayamolodost.ru21.06.2010