A series of recombinant vector DNAs containing the human full-size preproinsulin and apolipoprotein A1 genes in the integrative expression cassettes have been constructed in the Department. The mammalian cell lines that express the target human proteins were obtained. Vector DNA polyplexes based on modified polyethyleneimine containing glycoside ligands have been optimized for efficient and safe targeted gene transfer in mammalian liver cells. The consistently reproducible technique for obtaining experimental models of chemically induced diabetes in animals of four species (mice, rats, rabbits and pigs) has been perfected. The models of alimentary hypercholesterolemia and of lipid metabolism disorders under diabetes, induced by streptozotocin in rabbits, have been developed. Therapeutic efficacy of targeted vector DNAs has been demonstrated in long-term experiments with these animal models (Fig. 1): a) antihyperglycemic action of polyplexes containing human preproinsulin gene in the model of type 1 diabetes in mice, rats, rabbits and pigs; b) antiatherogenic effects of polyplexes containing human apolipoprotein A1 gene in the models of alimentary hypercholesterolemia and combined carbohydrate and lipid metabolism disorders in rabbits.