From Big Medical Encyclopedia

GENE THERAPY (Greek genos a sort, an origin + therapeia treatment) — the section of medical genetics developing in an experiment possible methods of treatment of hereditary diseases by correction of genetic defects. Is one of sections genetic engineering (see), the purposeful reconstruction studying experimental methods genomes (see) the lowest and the higher organisms. Premises for G.'s development were achievements of modern molecular genetics: preparative allocation of individual genes or their some fragments, the basic proof of a possibility of chemical and enzymatic synthesis of genes, the proof of a possibility of transgenesis from one organism in another. At the person it is known apprx. 2000 hereditary diseases, many of which are caused by genovariations (see. Mutation ). Big percent of hereditary diseases makes the exchange diseases caused by disturbance in structure of single genes, is a consequence of what or inefficiency of products controlled by a gene — enzyme, or total absence of production of specific enzyme (see. Enzymopathies ). Carry a fenilketonuriya, an argininemiya, a cystinuria to such diseases, etc. Relative correction of these enzymes is carried out, as a rule, by means of a dietotherapy.

Two possible ways of development were outlined G. Odin from them recognizes representation that all cells of an organism contain the identical volume of genetic information. The existing distinctions between cells of an organism are connected with the fact that in the course of a differentiation in different cells from the group responsible for manifestation of a sign, are switched off some genes (are repressed). It is supposed to find a possibility of substitution of gene defect in one fabrics by activation of the next normal, but repressed genes in other body tissues. Sinskhaymer (R. L. Sinsheimer, 1970) considers such possibility for G. of diabetes, believing that synthesis of insulin can be adjusted by implementation of genetic information of any cells of an organism (out of islets of Langerhans of a pancreas). The possibility of hormonal gene activation is known, in particular.

Other direction is connected with development of methods of entering of genetic information into cells of an organism for normalization of a genotype of the patient (replacement therapy). Possibilities of hybridization of cells are for this purpose studied, to-ruyu carry out on cellular cultures. An original method of hybridization was cell fusion by means of the inactivated virus of a parainfluenza like Sendai. Were even hybridized by such way far on biol, to an origin of a cell (people — a mosquito). The attempt of introduction of such hybridized cells cultivated on artificial environment in a human body is supposed. Also the methods of cellular surgery allowing to transplant kernels with the interesting genotype from somatic cells to nuclear-free egg are developed [Gerdon (J. Century of Gurdon), 1973].

The problem of introduction of the absent genetic information by means of viruses is especially perspective [S. Rogers, 1971]. Many viruses at infection of a cell do not harm it. Such types also are distinguished from the viruses infecting the person: SV40 virus, Shoup's papillomas, Sa7, etc. The SV40 virus was observed as pollution in vaccines, however its action on a human body was not shown. Shoup's virus causing formation of papilloma in rabbits does not give similar effects at the person, monkeys, dogs, rats, mice. This circumstance allows to use own genetic information of a virus or alien exogenous information introduced in its genome in G.

Possibilities of use of own information of viruses were shown by Rogers's works (from 1959 to 1971) on the example of a virus of papilloma of Shoup which bears in the genome information for synthesis of specific enzyme — arginases and is capable to induce production of this enzyme in other organisms. In particular, after intravenous administration of a virus to mice, rabbits, monkeys the level of arginine in blood at these animals decreased. The similar effect (low level of arginine in blood) was noted at the people conducting pilot studies with this virus. In 1975 Mr. Terkheggen (H. G. Tegheggen) with soavt, reported about attempt of treatment of three patients with a giperargininemiya with intravenous administration of a virus of Shoup; the effect observed at animals did not manage to be reached. No other impacts of this virus on an organism of animals and the person were observed. Merrill (Page R. Merrill) et al. (1971) successfully used a bacterial virus for transfer of genetic information in cells of skin of the person having a galactosemia, the fabrics which are grown up in culture. The galaktozny gene which is absent in cells was entered by means of a phage And, bearing a galaktozny operon of colibacillus. The gene of a bacterium began to work in cells of the person, synthesizing the necessary enzyme. So far this work did not receive confirmation at other experimenters, but the way planned by it is extremely important. Use of viruses as «carriers» of useful exogenous genetic information is perspective, edges it can be introduced in them by addition to their nucleinic to - those the coding sequences for specific enzymes. E.g., accession poly-And to RNA of a virus of a tobacco mosaic stimulates synthesis of a polylysine in plants. The virus allocated further from these plants continues to keep the acquired property throughout several passages. It is revealed also that polyornithine or a polylysine protect RNA of a virus of a tobacco mosaic from effect of ribonuclease. Therefore, adding various polypeptides, it is also possible to provide protection virus nucleinic to - you from action of cellular nucleases. Entering of a gene into «virus carrier» which could bring him to destination is possible by means of enzymatic reactions.

Development of methods G. is the perspective field of medical genetics, however its use on the person is connected with a number of difficulties and restrictions. It is unknown how the alien gene in a cell, biol will behave, feature a cut will not allow, obviously, to break its specificity and integrity genome (see); introduction of an alien gene will lead to emergence in a cell of a foreign protein, and, therefore, in an organism there will be a threat of an immunological havoc.

In 1972 the question of perspectives of use of G. was discussed at the meetings of WHO which confirmed prospects and importance of development of this new method of treatment of hereditary diseases. G.'s use in practice will be possible only after carrying out a number of basic pilot studies.

See also Hereditary diseases .

Bibliography: Physiological genetics, under the editorship of M. E. Lobashev and S. G. Inga-Vechto-mova, L., 1976, bibliogr.; Avery O. T., MacLeod C. M. a. McCarty M. Studies on chemical nature of substance inducing transformation of pneumococcal types, J. exp. Med., v. 79, p. 137, 1944; Mer ri 1 C. R., G e i e r M. R. a. P e t-Ticciani J. C. Bacterial virus gene expression in human cells, Nature (Lond.), v. 233, p. 398, 1971; Qasba P. K. a., A p o s h i a n H. V. DNA and gene therapy, Proc. nat. Acad. Sci. (Wash.), v. 68, p. 2345, 1971, bibliogr.; Rogers S. Gene therapy, Res. commun. ehem. path, pharma-col., v. 2, p. 587, 1971.

S. S. Kryazheva.