Biopolym. Cell. 1990; 6(1):12-31.
http://dx.doi.org/10.7124/bc.000244
Можливості генної терапії для лікування і профілактики масових патологій
1Кордюм В. А.
  1. Інститут молекулярної біології і генетики АН УСРС
    Київ, СРСР

Abstract

Аналізуються можливості генної терапії для лікування основних масових патологій людини-атеросклерозу, злоякісних пухлин, інфекційних хвороб і діабету. У своїй основі генна терапія поділяється на два напрямки: 1) виправлення генного дефекта і 2) генна компенсація функції. Перше базується на прецизійному заміщенні дефектного гена або його фрагмента і вимагає обов’язкового знання деталей ушкодження. Його найчастіше мають на увазі при згадці про генну терапію, але відносять майже винятково до класичних спадкових хвороб, у яких причиною хвороб є дефект конкретного структурного гена. Другий напрямок передбачає введення гена, покликаного компенсувати ослаблену (або в загальній формі змінену) функцію під спеціальною регуляцією. У цьому разі не обов'язковим є знання конкретного генного дефекта, що спричинив патологію. Оскільки в основі масових патологій найчастіше лежать дефекти, викликані невідомими порушеннями регуляції експресії неушкодженого структурного гена, їх можна нейтралізувати за принципом генної компенсації функції. Наводиться загальна схема генної терапії основних масових патологій і конкретні варіанти, що її пояснюють. Аналізується стан робіт з генної терапії основних масових патологій.
Повний текст: (PDF, російською)

References

[1] Kordium VA. Objectives and problems of gene therapy. Biopolym Cell. 1989; 5(2):5-16.
[2] Diamond JM. AIDS. Infectious, genetic or both? Nature. 1987 Jul 16-22;328(6127):199-200.
[3] Abel L, Demenais F. Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island. Am J Hum Genet. 1988;42(2):256-66.
[4] Diamond JM. AIDS. Infectious, genetic or both? Nature. 1987 Jul 16-22;328(6127):199-200.
[5] Goodfellow P, Stewart A. Human genetic disease--a new series in TIG. Trends Genet. 1988;4(5):123-4. Review.
[6] Tatevosov RB. Ecological problems of population development. Med geography and human ecology. Moscow. 1987; 39-54.
[7] Rotter JI, Diamond JM. What maintains the frequencies of human genetic diseases? Nature. 1987 Sep 24-30;329(6137):289-90.
[8] Mann DM. The pathological association between Down syndrome and Alzheimer disease. Mech Ageing Dev. 1988;43(2):99-136.
[9] Seidegard J, Pero RW. The genetic variation and the expression of human glutathione transferase mu. Klin Wochenschr. 1988;66 Suppl 11:125-6.
[10] Brown TW. Premature aging syndromes. Clin orient Int. symp. Eur. soc. dermatol. res. (Oslo, Febr. 7-8, 1986). Basel, 1987:152-165.
[11] Berg K. Genetic variation in low density lipoprotein. Beginning of a new era? J Immunogenet. 1985;12(6):263-5.
[12] Nei M., Saitou N. Genetic relationship of human populations and ethnic differences in reaction of drugs and food. Ethnic differ, react, drugs and xenobiotics: proc. meet. (Black Forest, Oct. 3-6, 1985). New York, 1986. 21-37.
[13] Paterson MC, Middlestadt MV, Weinfeld M, Mirzayans R, Gentner NE. Human cancer-prone disorders, abnormal carcinogen response, and defective DNA metabolism. Radiation Carcinogenesis and DNA Alterations NATO ASI Series, 1986; 124:471-98.
[14] Guttler F. Diagnosis of inherited metabolic disorders by DNA analysis. Med Lab Sci. 1985;42(4):326-32.
[15] Blum A., Motinier A. La mortalite en Union Sovietique. Popul. et soc. 1988. N 223. 1-4.
[16] Fiolka L. Some problems with sex differences in mortality. Z Gesamte Hyg. 1988;34(8):447-9.
[17] Humphries IS, Wile D, Taylor R et al. Which genes cause hyperlipidaemia and atherosclerosis? Biotech. RIAr 88: Mol. probes: technol med. appl.: proc. Int. symp. (Florence, Apr. 11-13, 1988). New York, 1988:13.
[18] Repin BS. Modern molecular cellular bases lipoprotein theory of atherosclerosis. Moscow: VNIIMI, 1987; 68 p.
[19] Croce CM. Molecular genetics of human leukemias and lymphomas. AIDS Res Hum Retroviruses. 1987;3 Suppl 1:229-34.
[20] Masuda H, Battifora H, Yokota J, Meltzer S, Cline MJ. Specificity of proto-oncogene amplification in human malignant diseases. Mol Biol Med. 1987;4(4):213-27.
[21] Friend SH, Dryja TP, Weinberg RA. Oncogenes and tumor-suppressing genes. N Engl J Med. 1988;318(10):618-22.
[22] Weinberg RA. Finding the anti-oncogene. Sci Am. 1988;259(3):44-51.
[23] Nebert D., Gonzales FJ. P450 genes: structure, evolution, regulation and relationship to cancer. 6 2 1 st meet. Biochem. Soc. (London, 17-19 Dec., 1986): Abstr. London, 1986: 33.
[24] Kopelovich L. The transformed (initiated) human cell phenotype: study of cultured skin fibroblasts from individuals predisposed to cancer. Mutat Res. 1988;199(2):369-85.
[25] Le Beau MM, Pettenati MJ, Lemons RS, Diaz MO, Westbrook CA, Larson RA, Sherr CJ, Rowley JD. Assignment of the GM-CSF, CSF-1, and FMS genes to human chromosome 5 provides evidence for linkage of a family of genes regulating hematopoiesis and for their involvement in the deletion (5q) in myeloid disorders. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 2:899-909.
[26] Diaz MO, Ziemin S, Le Beau MM, Pitha P, Smith SD, Chilcote RR, Rowley JD. Homozygous deletion of the alpha- and beta 1-interferon genes in human leukemia and derived cell lines. Proc Natl Acad Sci U S A. 1988;85(14):5259-63.
[27] Internationul symposium hears promising news on TNE. Pract Biotechnol. 1986; 7(12):3-4.
[28] Blay J, Bertoglio J, Gay F et al. Interaction fonctionnelle entre le TNF et l IL-2 an de l'induction de l'activite cytotxique LAK. C r Acad Sci C. 1988; 307(2):47-51.
[29] Roche reveals interferon, IL-2 results. Biotechnol News. 1988; 8(4):7.
[30] Recombinant interleukin-2 and antitumor therapy. Drug License Opport. 1988; 10(10):419.
[31] Golovachev V. Pill in the ribs. Economic Newspaper. 1988. (36):19.
[32] Mandas R, Forno B, De Maria W. Infezioni virali e malattia diabetica. G Batteriol Virol Immunol. 1985. 78(1-6):60-9.
[33] Gu XF, Elion J, Ouagued M, Clauser E, Assan R, Krishnamoorthy R. A simple strategy to amplify specifically the HLA-DQ beta gene region with genomic DNA as template. FEBS Lett. 1988;236(1):23-6.
[34] Ikeda T, Lever AM, Thomas HC. Evidence for a deficiency of interferon production in patients with chronic hepatitis B virus infection acquired in adult life. Hepatology. 1986;6(5):962-5.
[35] Bluger AF, Veksler KhM. New aspects of viral-immunogenetic pathogenesis concept of viral hepatitis. New in hematology: methods, factors concept. Riga, 1988; 15-40.
[36] Parshina OV, Savitskii GI, Nosik NN, Ketiladze ES, Ershov FI. The interferon system in viral hepatitis B. Vopr Virusol. 1988;33(5):610-2.
[37] Shindo M, Okuno T, Matsumoto M, Takeda M, Takino T, Sokawa J, Iwata A, Sokawa Y. Serum 2',5'-oligoadenylate synthetase activity during interferon treatment of chronic hepatitis B. Hepatology. 1988;8(2):366-70.
[38] Patton JS, Shepard HM, Wilking H, Lewis G, Aggarwal BB, Eessalu TE, Gavin LA, Grunfeld C. Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells. Proc Natl Acad Sci U S A. 1986;83(21):8313-7.
[39] Cetus combines two anticancer products in human testing. Three related patents issue. Biotechnol Law Rept. 1987; 6(4):289-347.
[40] Thivolet C, Trepo C. Virus and insulin-dependent diabetes mellitus. Etiopathogenic perspectives. Pathol Biol (Paris). 1988;36(2):182-6.
[41] Csonka E, Batter PI, Varadi G. Viruses as risk factors in the pathogenesis of atherosclerosis. Pathol Res Pract. 1987; 182(4): 480.
[42] Boehm BO, Scherbaum WA. Pfeiffer EF, Schoffling K. Immunogenetik des Typ-I-(insulininpilichtigen) Diabetes mellitus. Med Klin. 1987; 82(12-1)3:439-42.
[43] Butenko GM, Zaĭchenko AP. Role of age-related changes in immunity in the pathogenesis of atherosclerosis. Vestn Akad Med Nauk SSSR. 1986;(10):31-5.
[44] TNF in murine systemic autoimmune lupus nephritis. Drug License Opport. 1988; 10(3):107.
[45] Samid D, Friedman RM. Transcriptional regulation of ras by interferon. Interferons cell growth inhibitors and antitumor fact.: Proc. Schering corp. UCLA symp. (Colo, Apr. 6-12, 1986). New York, 1986:413-22.
[46] Yarden A, Kimchi A. Tumor necrosis factor reduces c-myc expression and cooperates with interferon-gamma in HeLa cells. Science. 1986;234(4782):1419-21.
[47] Krönke M, Schlüter C, Pfizenmaier K. Tumor necrosis factor inhibits MYC expression in HL-60 cells at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1987;84(2):469-73.
[48] Seliger B, Kruppa G, Schäfer R, Redmond SM, Pfizenmaier K. Gamma interferon regulates long terminal repeat-controlled oncogene expression in transformed mouse fibroblasts at the level of mRNA transcription. J Virol. 1988;62(2):619-21.
[49] Gerfaux J, Sergiescu D, Vignal M. et al. Stable reversion to non malignancy by long term interferon treatment of cells expressing the c-mos oncogene. Interferons cell growth inhibitors and antitumor fact. : Proc. Schcring corp. UCLA symp. (Colo, Apr. 6-12, 1986) - New York, 1986; 377-89.
[50] Contente S, Kenyon K, Samid D, Friedman RM. Altered gene expression in oncogenc-transformed mouse cells persistently reverted by prolonged interferon treatment. J Cell Biochem. 1988; (Suppl. 12A):211.
[51] Hosang M. Recombinant interferon-gamma inhibits the mitogenic effect of platelet-derived growth factor at a level distal to the growth factor receptor. J Cell Physiol. 1988;134(3):396-404.
[52] Rosenthal J. Aging and the cardiovascular system. Gerontology. 1987;33 Suppl 1:3-8.
[53] Czaja MJ, Weiner FR, Kirwin MS, Zern MA. Effects of gamma interferon on collagen gene expression. Hepatology. 1986; 6(5):1199.
[54] Nakagawa H, Kitagawa H, Aikawa Y. Tumor necrosis factor stimulates gelatinase and collagenase production by granulation tissue in culture. Biochem Biophys Res Commun. 1987;142(3):791-7.
[55] Kahari VM, Heino J, Vuorio T, Vuorio E. Interferon-alpha and interferon-gamma reduce excessive collagen synthesis and procollagen mRNA levels of scleroderma fibroblasts in culture. Biochim Biophys Acta. 1988;968(1):45-50.
[56] Myagkaya IP, Gyulling EV, Gandzha IM. Age T-immunodeficiency and atherosclerosis. Gerontology and geriatrics; immunity and aging. Kyiv, 1987; 103-10.
[57] Cohen JJ, Duke RC, Chervenak R et al. DNA fragmentation in targets of CTL: an example of programmed cell death in the immune system Mech . cell-mediat. cytotoxicity II: Proc. 2 Int. workshop (Annapolis, Md, June 10-13, 1984). New- York; London, 1985:493-506.
[58] Mellies MJ, Laskarzewski PM, Tracy T, Glueck CJ. Tracking of high- and low-density-lipoprotein cholesterol from childhood to young adulthood in a single large kindred with familial hypercholesterolemia. Metabolism. 1985;34(8):747-53.
[59] Romies I. The role of HDL in the pathogenesis of arteriosclerosis. Fat Sci., 1983: Proc. 16th ISF congr. (Budapest, 4-7 Oct., 1983). Budapest, 1985. Pt B:819-24.
[60] Sasaki A, Matsumiya K, Arao M. et al. High-density lipoprotein cholesterol and its protective role against the development of coronary heart disease in Japanese diabetics. J Jap Diabet. Soc. 1984; 27(10:1067-74.
[61] Gorb GD, Grushko IV, Zhdanyuk YuI, Makovskaya TE. Peculiarities disorders of immunological reactivity in patients with coronary heart disease in elderly and senile. Epidemiological, clinical and biochemical and social aspects of longevity in Siberia: Proc. of reports. Sib. conf. (Novosibirsk, January 23., 1987). Novosibirsk, 1986; 37-8.
[62] Traill KN, Jurgens G, Bock G, Wick G. Paradoxical increase in low density lipoprotein uptake by freshly isolated lymphocytes from the elderly Age. 1987; 10(3):111.
[63] Patsch W, Gotto AM Jr, Patsch JR. Effects of insulin on lipoprotein secretion in rat hepatocyte cultures. The role of the insulin receptor. J Biol Chem. 1986;261(21):9603-6.
[64] Kawakami M, Murase T, Ogawa H, Ishibashi S, Mori N, Takaku F, Shibata S. Human recombinant TNF suppresses lipoprotein lipase activity and stimulates lipolysis in 3T3-L1 cells. J Biochem. 1987;101(2):331-8.
[65] Larrick JW, Ringold CM, Mark DF et al. Use of tumor necrosis factor as a weight regulator. Biotechnol Adv. 1987; 5(1):191.
[66] Le TNF a la chasse aus kilos? Biofectur. 1987;57:11-12.
[67] Holter W, Grunow R, Stockinger H, Knapp W. Recombinant interferon-gamma induces interleukin 2 receptors on human peripheral blood monocytes. J Immunol. 1986;136(6):2171-5.
[68] TNF stimulates tumor growth. Drug License Opport. 1988; 10(8):311.
[69] Chard T, Craig PH, Menabawey M, Lee C. Alpha interferon in human pregnancy. Br J Obstet Gynaecol. 1986;93(11):1145-9.
[70] Shiozawa S, Chihara K, Shiozawa K, Fujita T, Ikegami H, Koyama S, Kurimoto M. A sensitive radioimmunoassay for alpha-interferon: circulating alpha-interferon-like substance in the plasma of healthy individuals and rheumatoid arthritis patients. Clin Exp Immunol. 1986;66(1):77-87.
[71] Rowley AH, Shulman ST, Preble OT, Poiesz BJ, Ehrlich GD, Sullivan JR. Serum interferon concentrations and retroviral serology in Kawasaki syndrome. Pediatr Infect Dis J. 1988;7(9):663-6.
[72] Cerami A, Beutler B. Cachectin: the dark side of tumor necrosis factor. Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:625-9.
[73] Brown TD, Koeller J, Beougher K, Golando J, Bonnem EM, Spiegel RJ, Von Hoff DD. A phase I clinical trial of recombinant DNA gamma interferon. J Clin Oncol. 1987;5(5):790-8.
[74] Retrovirus infected skin cells deliver drugs. Biotechnol News. 1988; 8(13):5.
[75] Roberts L. New targets for human gene therapy. Science. 1988;241(4868):906-906.
[76] Miller AD, Adam MA, Osborne WR. Retrovirus-mediated gene transfer into human skin fibroblasts. Viral Vectors: Conf. (Cold Spring Harbor., March, 1988). New York : Cold Spring Harbor Lab., 1988:122-6.
[77] Palca J. Gene transfer to humans approved in face of advice. Nature. 1988;335(6191):577.
[78] Joyce C. Americans plan gene therapy on people. New Sci. 1988; 119(1624):24.
[79] Askonas BA. Vector-directed interleukin expression and infection. Nature. 1987 Nov 19-25;330(6145):206.
[80] Ezekowitz RA, Dinauer MC, Jaffe HS, Orkin SH, Newburger PE. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med. 1988;319(3):146-51.
[81] Dopfer R, Niethammer D, Peter HH, Kniep EM, Monner DA, Muhlradt PF. In vivo effects of interleukin 2 on lymphocyte subpopulations in a patient with a combined immunodeficiency. Immunobiology. 1984;167(5):452-61.
[82] Faist E, Ertel W, Mewes A. Moglichkeiten der Immunmodulation bei chirurgischen Patienten. Allergologie. 1988; 11(9):344-53.
[83] Lopez-Cepero M, Specter S, Matteucci D, Friedman H, Bendinelli M. Altered interleukin production during Friend leukemia virus infection. Proc Soc Exp Biol Med. 1988;188(3):353-63.
[84] Yaita H, Yasumoto K, Nagashima A, Sugimachi K, Nomoto K. Antitumor activity of regional lymph node lymphocytes in patients with lung cancer. J Surg Oncol. 1988;38(3):165-72.
[85] Hartwig M. Restauration des Immunstatus durch Interlcukin-2. Alternforsch. 1988; 43(3):133-6.
[86] Ershler WB, Moore AL, Roessner K, Ranges GE. Interlcukin-2 and aging: decreased interlcukin-2 production in healthy older peopledoes not correlate with reduced helper cell numbers or antibody response to influenza vaccine and is not corrected in vitro by thymosin cci. Immunopharmacology. 1985. 10(1):11 -7.
[87] Neborachko LN, Lukash LL, Varzanova IS, Kordiutn VA. Studies in expression of human exogenous insulin gene under control of regulatory region of hsp70 dr. melanogaster gene in human fibroblasts. Biopolym Cell. 1990; 6(1):88-90,106.
[88] Shennan KI, Docherty K. Expression of normal and mutant human pre-pro-insulins in Xenopus oocytes. Biochimie. 1988;70(1):99-107.
[89] Neborachko LN, Lukash LL, Troyanovsky BM, Varzanova IS, Buzhievskaya TI, Kordium VA. Studies in possibility of expression of exogenic human insulin gene in cultured mammalian fibroblasts. Biopolym Cell. 1989; 5(2):58-61.
[90] Lukash LL, Neborachko LN, Sukhorada EM, Usenko EV, Varsanova IS, Podolskaya SV, Buzhievskaya TI, Kordium VA. Human insulin gene expression in cultured mammalian cells Biopolym Cell. 1990; 6(1):82-7.
[91] Brinster RL, Allen JM, Behringer RR, Gelinas RE, Palmiter RD. Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci U S A. 1988;85(3):836-40.
[92] Madsen OD, Andersen LC, Michelsen B, Owerbach D, Larsson LI, Lernmark A, Steiner DF. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo. Proc Natl Acad Sci U S A. 1988;85(18):6652-6.
[93] Enzo Biochem. (New York, NY) working on method of gene therapy to inhibit growth of viruses. Appl Genet News. 1987; 8(1):8-9.
[94] Corcoran E. Gene therapy in gestation. Three companies hope to turn it into medical reality. Sci. Amer. 1988; 259(5):98-98B.
[95] Two US companies move into gene therapy. Drug License Opport. 1988. 10(3):104.