San Raffaele Telethon Institute for Gene Therapy

Pathogenesis and treatment of immune and bone diseases


Group leader

Anna Villa


Our work is focused on the pathophysiology and development of novel cellular therapies to cure severe combined immunodeficiencies caused by RAG genes and inherited bone defects due to osteoclast dysfunction.

Research activity

Genetic mutations in RAG genes cause a broad spectrum of clinical manifestations including T- B- SCID, Omenn syndrome, atypical SCID and combined immunodeficiency with granuloma/autoimmunity (CID-G/AI). The main goal of our research is to develop a platform to treat RAG1 defect by exploiting gene editing approach in hematopoietic stem and progenitor cells (HSPC) carrying null or hypomorphic RAG defects and testing novel conditioning regimen based on the use of biological compounds to preserve tissue integrity.

In parallel to cure Autosomal Recessive Osteopetrosis (ARO) caused by defects in osteoclast function, we have optimized a novel platform of gene therapy coupling lentiviral gene transduction with HSPC expansion. We plan to dissect the molecular and cellular heterogeneity of hematopoietic stem and progenitor cells spontaneously circulating in the peripheral blood of ARO patients and evaluate the effect of repeated infections on hematopoietic stem cell stemness and quiescence.