San Raffaele Telethon Institute for Gene Therapy

Liver gene therapy


Group leader

Alessio Cantore


We are a young and dynamic group that focuses on the biotechnological aspects and translational applications of liver-directed gene transfer and editing. We investigate lentiviral vector (LV)-mediated liver gene transfer and its stability following post-natal liver growth, homeostatic turnover, tissue damage and evaluate different gene therapy strategies in preclinical models of hemophilia and liver metabolic diseases, with the ultimate goal of devising advanced gene therapy products as novel treatments for affected patients.

Research activity

Our research focuses on three areas:

Gene therapy for hemophilia. The overall objectives of this area are: i) to bring LV-mediated liver gene therapy to first-in-human testing in people with severe hemophilia, ii) to continue development of improved LV and administration protocols for liver-directed gene therapy, iii) to support development of improved manufacturing processes.

Liver tissue dynamics. The overall objective of this area is to dissect the role of different liver cell populations in post-natal liver growth, homeostatic renewal and response to damage. Successful liver gene therapy for inherited monogenic diseases provides safe, therapeutic, life-long replacement of the missing function to pediatric patients. To achieve this goal, the therapeutic genetic modification needs to survive physiological post-natal growth, homeostatic turnover in adulthood and potentially regeneration following tissue damage. Thus, it is necessary to identify and target the therapy to the cell populations contributing to these processes in the liver.

Liver metabolic diseases. The overall goal of this area is to define and tailor the best gene therapy strategy for metabolic liver diseases. One aim is to further investigate which biological barriers limit in vivo liver gene transfer and how to overcome them. The second aim is to determine the threshold of genetically corrected hepatocytes required for disease correction and assess whether cross-correction or selective advantage occur in animal models of metabolic diseases. A third aim is to compare advanced LV-mediated gene delivery and site-specific nuclease mediated gene editing in terms of efficiency, therapeutic efficacy, safety and durability and define the most suitable therapeutic indication among metabolic liver diseases.