Andrés Fernando MURO, PhD - "Liver-Directed Gene Therapy for Inborn Errors of Metabolism"

Inborn errors of metabolism (IEM) are caused by mutations in genes involved in metabolic pathways. Most of which currently lack a cure. Existing treatments primarily focus on symptom management rather than correcting the underlying genetic defect, often remaining inadequate and limited in effectiveness.

Being a central organ in metabolism, many of these conditions occur in the liver, which is also an attractive organ for gene therapy because of its role in many essential metabolic functions, the natural hepatic tropism of many gene therapy vectors, its high vascularization and tolerogenic properties, and its capacity to act as a protein biofactory.

The talk will highlight liver-directed gene therapy approaches of IEM developed in our laboratory, with particular focus on the Crigler-Najjar syndrome type I (CNSI) and Fabry disease, using relevant mouse models of the diseases. I will discuss AAV-mediated gene replacement therapy and genome targeting strategies for the treatment of these conditions in both neonates and adults, considering factors such as vector re-administration and the proliferative status of hepatocytes.