Recombinant viral vectors containing the human urogenase plasminogen activator gene and their use in the treatment of hepatitis fibrosis

摘要

Preparing recombinant (non-)viral vectors (A) by cloning reporter gene (RG), and modified cDNA (I) of a therapeutic gene (II) that encodes a protein (III) useful for treating fibrosis (hepatic, pulmonary, renal, cardiac or pancreatic), keloids and hypertrophic scars in mammals, including humans, is new. An independent claim is also included for a recombinant adenoviral vector (A') produced by the new method. ACTIVITY : Hepatotropic; Antifibrotic; Vulnerary. MECHANISM OF ACTION : (II) induce degradation of collagen. Liver cirrhosis was induced in rats using tetrachloromethane, then the animals injected (iliac vein) with a single dose of 6X10 1 1 viral particles/kg of vector pAd.PGk-delta Ndelta C-huPA (expressing human urokinase). Analysis of the liver after 8 days indicated levels (international units/l) of ALT, AST and alkaline phosphatase of 88.5, 137 and 205; compare 410, 2250 and 454 for animals injected with an irrelevant vector; and total bilirubin was 0.94 (compare 1.4) mg/dl. Hematological parameters were not affected and the treatment significantly increased expression of matrix metalloprotease-2; reduced expression of collagens types I, III and IV, and stimulated mitosis of hepatocytes.