Pasquale Piccolo, PhDAssistant Investigator
Telethon Institute of Genetics and Medicine (TIGEM)
Naples, ItalyShort CVAbstarct
Adeno-associated vectors (AAV) have achieved remarkable successes in the clinics, and liver-directed gene therapy clinical trials are currently ongoing for several inborn errors of metabolism. However, ongoing clinical trials mostly address diseases that are not associated with significant hepatic damage. Features associated with liver injury, like fibrosis, hepatocyte proliferation, and increased risk of hepatocellular carcinoma represent significant hurdles toward effective and safe AAV-mediated gene therapy for these disorders.
In my lab we have been studying the effect of fibrosis on liver-directed gene therapy mediated by AAV vectors and in this talk, I will show how fibrosis hampers hepatocyte transduction by AAV in several mouse models. We hold a particular interest in Wilson disease, which is characterized by copper-dependent hepatocellular damage due to mutation in ATP7B copper transporter and is among the most frequent genetic causes of liver failure. I will present our efforts to develop novel gene therapy approaches for this disorder that overcome the limitations posed by lived injury and AAV cargo capacity.