About

The overall aim of AAVolution is to develop and implement innovative therapeutic tools in the field of liver-directed AAV gene therapy approaches. We anticipate that the technological breakthroughs proposed here will pave the way to overcome current limitations not only in hepatic diseases, but also in other genetic conditions that are suitable for liver-directed gene therapy.

Importantly, AAVolution aims to address three key aspects of liver gene therapy with AAV vectors, which are:

• (to overcome transient AAV-mediated expression in proliferating hepatocytes, i.e. newborn or regenerating livers, by applying novel CRISPR-Cas technology or developing autonomously-replicating AAVs;
• to improve liver transduction with novel AAV serotypes which enhance the potency of the gene delivery system while reducing the toxicity of the entire procedure at patient level;
• to overcome pre-existing immunity to AAVs by transiently reducing the levels of circulating anti-AAV neutralizing antibodies, which currently preclude its systemic delivery in about 50% of individuals.