Prospects for gene therapy Gene therapy is the replacement of defective (negative) genes with normal ones. It also includes the use of genes to treat diabetes and AIDS. The question of the possibility of treating hereditary diseases arose as soon as scientists developed ways to transfer genes into specific cells, where they are transcribed and translated. The question also arose: which patients should be treated first - those with more or better understood diseases? Most people were inclined to believe that gene therapy should be developed for those diseases about which more is known: the affected gene, protein, and tissue of their localization are known. This, in particular, was the case with severe immunodeficiency associated with the lack of the enzyme adenosine deaminase (ADA) in the body. As a result of ADA deficiency, the formation of T and B lymphocytes in a child is disrupted and he or she becomes completely defenseless against bacteria and viruses. Against the background of large financial costs, a therapeutic effect has been obtained in sick children as a result of the introduction of the ADA gene. However, several dozen such children are born every year. Currently, much attention is being paid to research on gene therapy for diseases affecting many people: hypertension, high cholesterol, diabetes, some forms of cancer, etc.
Given that gene therapy is associated with changes in the human hereditary apparatus, special requirements are needed for clinical trials: 1) clear knowledge of the gene defect and how the symptoms of the disease are formed; 2) reproduction of the genetic model in animals; 3) the absence of alternative therapy, or the existing therapy is impossible or ineffective; 4) safety for the patient.
The development of gene therapy also addresses the following issues:
1) which cells should be used? 2) what part of the cells should be treated to reduce or stop the progression of the disease? 3) will overexpression of the introduced gene be dangerous? 4) is it safe for the reconstructed gene to enter other tissues? 5) how long will the altered cell function? 6) will the new cells be attacked by the immune system?
Hereditary gene therapy is transgenic and changes all cells in the body. It is not used in humans. Nonhereditary (somatic) gene therapy corrects only somatic cells affected by a genetic defect. Non-hereditary gene therapy can help an individual, but it will not improve the condition of future generations, because the mutant gene is not changed in the gametes. Unfortunately, little is known about most hereditary diseases. In cases where it is known which tissues are affected, it is difficult to introduce a normal gene into them. Despite this, medical genetics has made significant progress in the treatment of certain diseases. Two approaches are used for this purpose. The first one involves isolating cells from the patient's body to introduce the necessary gene into them (ex vivo gene therapy), after which they are returned to the patient's body. Retroviruses containing genetic information in the form of RNA are used as a vector. The retrovirus is provided with recombinant RNA (RNA of the virus + RNA copy of the human gene). After the recombinant RNA enters a human cell, for example, a red bone marrow stem cell, reverse transcription occurs and the recombinant DNA carrying the normal gene enters the human chromosome. Unfortunately, little is known about most hereditary diseases. In cases where it is known which tissues are affected, it is difficult to introduce a normal gene into them. Despite this, medical genetics has made significant progress in the treatment of certain diseases. Two approaches are used for this purpose. The first one involves isolating cells from the patient's body to introduce the necessary gene into them (ex vivo gene therapy), after which they are returned to the patient's body. Retroviruses containing genetic information in the form of RNA are used as a vector. The retrovirus is provided with recombinant RNA (virus RNA + RNA copy of a human gene). After the recombinant RNA enters a human cell, for example, a red bone marrow stem cell, reverse transcription occurs and the recombinant DNA carrying the normal gene enters the human chromosome. This is how several children were treated for the above-mentioned severe immunodeficiency due to the absence of ADA. At the same time, they obtained the ADA enzyme isolated from cows as a therapeutic drug. Using the adenovirus (AVV) as a vector, scientists have developed a method of gene therapy for sickle cell disease. Under natural conditions, AVV affects only those red bone marrow cells that are precursors of red blood cells. A functional β-globin gene was introduced into AVV, and the virus transferred it to immature red blood cells. The latter are filled with normal hemoglobin and sent into the bloodstream. Another approach to gene therapy involves the use of viruses, laboratory-grown cells, and even artificial carriers to introduce genes directly into the patient's body. When a patient inhales an aerosolized suspension, the virus enters the lung cells and brings a functional cystic fibrosis gene to them. If the cells are resistant to genetic manipulation, scientists affect the cells next to them. The latter have an effect on cells defective in a particular gene. For example, gene therapy is being tested in mice with damage to the same part of the brain as in patients with Alzheimer's disease. The gene for nerve growth factor penetrates into fibroblasts. These cells are implanted into the brain section and secrete the growth factor that neurons need. Neurons begin to grow and produce the appropriate neurotransmitters. It is assumed that a similar type of gene therapy can be used to treat Huntington's disease, Parkinson's disease, depression, etc.
Some success has been achieved in the use of gene therapy in the treatment of malignant tumors. A tumor cell is isolated and genes encoding anti-cancer substances of the immune system, such as interferons and interleukins, are introduced into it. Re-introduced into the tumor, the cells begin to produce these substances, killing themselves and the surrounding malignant cells. |
