| 摘要 |
FIELD: medicine, therapy. SUBSTANCE: invention relates to therapeutic induction of apoptosis in activated inflammatory cells or cells in inflammatory focus by administration in these cells chimeric gene comprising gene inducing apoptosis (AIG) that is regulated by promoter of inducible gene activating in the process of inflammation and promoter enhancer resulting to conversion of cells to targets. In one variant of invention chimeric gene comprises at least one enhancer of promoter TNFalpha bound to functional copy of minimal promoter TNFalpha and bound to at least one copy of gene inducing apoptosis being expression of gene is regulated by promoter TNFalpha. Binding can be direct, distal or proximal or their combination. Gene examples inducing apoptosis are caspase-3 gene, caspase-4 gene, caspase-5 gene, Granzym B. It is preferably that chimeric gene TNFp-AIG would be expressed only in cells that produce inflammatory cytokine TNFalpha. Except for, chimeric gene TNFp-AIG isolates also inducible factors of TNFp-transcription that results to decrease of endogenous production of TNFalpha. Invention relates also to methods of preparing and application of self-regulating chimeric genes inducing apoptosis and pharmaceutical composition comprising thereof and designated for treatment of inflammatory diseases. The advantage of invention involves the development of agents used for prolonged treatment associated with reduction of by-side effect. EFFECT: valuable medicinal properties of therapy. 30 cl, 10 dwg, 4 ex _
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