Hepatocyte-directed gene therapy for Wilson disease

Several liver genetic disorders are characterized by advanced fibrosis or cirrhosis. Among them, Wilson Disease (WD) is the most frequent and is caused by mutations in ATP7B, encoding for a P-type copper transporting ATPase expressed in the hepatocytes. Our efforts are focused on the development of a liver-directed gene therapy for WD using rAAV bearing engineered ATP7B, size-optimized expression cassettes or dual rAAV vector systems. We are combining these gene replacement approaches with anti-fibrotic therapy using microRNAs to reduce fibrosis and achieve clinically effective transduction levels. The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.