M.N. Evseeva - Post-graduate Student, Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University. E-mail: yrubtsov@gmail.com, 6gadfly9@gmail.com Y.P. Rubtsov - Ph.D. (Chem.), Assosiate Professor, Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University

Liver fibrosis is caused by deposition of extracellular matrix (ECM) proteins in chronically damaged due to toxic or infectious stress liver parenchyma. These deposits disrupt access to blood supply and negatively affect hepatocyte functioning. We designed gene-therapeutic approach based on non-viral delivery of human hepatocyte growth factor (HGF) and urokinase (uPA) genes into mouse liver. Combination of these genes was chosen because HGF stimulates hepatocyte proliferation and uPA down-regulates production and increases degradation of ECM proteins in the liver. By using optimized gene delivery protocol we achieved high level of therapeutic gene expression in mouse liver. Biochemical and histological evaluation proved efficacy and safety of HGF and uPA gene combination for treatment of established experimental liver fibrosis.

 

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