Biopolymers and cell. 1993. Volume 9. № 4. 63 - 104

V. A. Kordyum, V. V. Frolkis, L. L. Lukash, V. N. Shulzhenko, S. P. Shpilevaya, I. E. Kostetsky, T. G. Titok, I. S. Varsanova, L. I. Likhacheva, D. M. Irodov

Gene Therapy of Mass Pathologies

Summary

    The whole complex of investigations is described that allows to run the way from the idea to experimental realization of a fundamental possibility of gene therapy and its application to mass pathologies on the sample of insulin-dependent diabetes and athe¬rosclerosis. The search and analysis were performed of such regulatory elements that whould permit an expression irrespective of the state of a general cell regulation. Expression of the implanted gene material is shown on cells of different tissues and different organisms and also in vivo (both the model gene of $-galactosidase Esche-richia coli and insulin- and apolipoprotein high density Al-coding genes related to above stated pathologies). It is concluded that the results obtained in the culture outsi¬de the organisms shouldn't be extrapolated on the animals, i. e. on the organism's level. The expression of recombinant molecules is shown to be ambiguous and depend on gene's surroundings and the type of recipient cells. Both in the culture and in the organism the individual cell heterogeneity is observed in the quantitative characteristics of the expression of gene implanted from outside. Besides, an individual organism and age heterogeneity with regard to the expression of the exogenous gene is reported. The conclusion is made about the necessity to individualize gene therapy of mass pathologies.