Registration Number
0213U002187,
0110U006123
, R & D reports
Title
Fundamental foundations multigene therapy for mass pathology with complications
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Head
Kordium Vitalii Arnoldovich, Доктор біологічних наук
Registration Date
17-01-2013
Organization
Institute of Molecular Biology and Genetics
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For the estimation of effectivity of experimental gene therapy for atherosclerosis against diabetes in rabbits we have carried out simulations disorders of carbohydrate and lipid metabolism in the experiment. Studying the influence of dose and administration multiplicity streptozotoucin (STC) in rabbits to produce moderate chronic diabetes results in development of the STC scheme daily administration at a dose of 50 mg / kg of animal body mass for 3 days. Experimental hypercholesterolemia in intact animal (model of alimentary cholesterol atherosclerosis) and in mild diabetic rabbits (hyperglycemia - up to 12 mmol/l glucose) was generated by supplementary daily feeding of pure cholesterol ( 2% ) in sunflower seed oil ( 15% ) for 5 weeks. Developed combined model of cholesterol dyslipidemia on a background of chronic hyperglycemia in rabbits is the high atherogenic, as evidenced by the increase atherogenicity index on average, to 13 in 5 weeks of cholesterol load. Analysis of the lipid profile of diabetic animals for modeling allowed to diagnose rapidly progressive changes characteristic of diabetic dyslipidemia. The latter is characterized by rising levels of triglycerides 1.8 times, atherogenic low-density lipoprotein cholesterol in 4.7 times, very low density lipoproteins cholesterol in 2.2 times and a significant reduction in antiatherogenic HDL in 1.9 times. The resulting model was suitable to study the effectiveness of new therapies atherosclerosis, namely antiatherogenic therapeutic DNA, since it requires three times less time to simulate pathology than other experimental models of alimentary hypercholesterolemia, and will be used by the authors in experiments with gene therapy for atherosclerosis. The transfection experiment with use nonviral gene delivery system on basis of lactosilated polyethylenimine have been performed, The non-viral gene delivery system have been optimized in vivo. The molar ratio of DNA / polycation required for the formation of еру complexes have been selected by method of gel retardation. The polyplexes with marker and target vector DNA for targeted gene transfer in mammalian liver cells in vivo based on modified poly (L-PEI) containing glycoside ligands were designed. It was found that glycosylation of PEI reduces its cytotoxic effects at rather high concentrations polyplex 1.8 times. Efficiency of formation complexes L-PEI with vector plasmid DNA formation under different ratios of DNA / transfection reagent have been identified.
Product Description
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Iродов Дмитро Михайлович
Гулько Тамара Павлывна
Моргунов Павло Вікторович
Похоленко Яніна Олександрівна
Рубан Т.П.
Сухорада О.М.
Топорова Олена Карнеліївна
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2020-04-02
