Abstract: The invention encompasses the use of gene therapy for the treatment of different kinds of fibrosis in human beings. Specifically, the invention encompasses the use of therapeutic genes specifically directed to target organs to revert and/or prevent the development of the fibrosis process. The invention further encompasses genes encoding for proteins including human MMP-8 active and latent, MMP-1, MMP-2, MMP-9 and MMP-13; human uPA wild type and/or modified (or its truncated version), the truncated receptor for TGF-? type II and Smad-7, which can be directed by adenovirus and/or other recombinant vectors that cannot transduce (i.e., infect) others organs. The gene therapy of the invention further encompasses treating disorders including renal fibrosis, pulmonary fibrosis, hypertrophic and keloid scars (i.e., skin fibrosis), and other kinds of fibrosis.

Abstract: The present invention relates to recombinant adenoviral vectors bearing exogenous genes that encode for therapeutic proteins useful in the treatment of hepatic cirrhosis and generalized fibrosis, such as renal fibrosis, pulmonary fibrosis, hypertrophic scars and keloid of the skin, and/or in other target organs susceptible to suffer from it. The invention also relates to a mechanism of tissue-specific recognition of the affected cells by means of delivery of therapeutic genes to cirrhotic organs.

Abstract: The present invention encompasses a modified human urokinase plasminogen activator (“huPA”) gene, which was inserted in the adenoviral vector (pAd-.DELTA.huPA), which is not secreted and does not provoke hypercoagulation or spontaneous internal bleeding. It has been discovered that huPa induced a dramatic fibrosis reduction (85%) on day 10 of vector administration, compared to control cirrhotic rats and 55% hepatocyte proliferation increase. Liver function tests (ALT, AST, alkaline phosphatase and bilirubin) dropped to nearly normal levels and hepatocyte proliferation was observed. The invention also encompasses gene therapy with modified huPA to treat disorders in patients. In a particular embodiment, the invention encompasses a treatment for patients with liver cirrhosis.