San Raffaele Telethon Institute for Gene Therapy

Pathogenesis and therapy of primary immunodeficiencies


Head of Unit

Alessandro Aiuti


Primary Immunodeficiencies (PIDs) are a group of rare genetic diseases characterized by an altered innate and adaptive immune system, leading to increased susceptibility to infections, risk of autoimmunity and cancer. Without treatment, many of these conditions are fatal and require early intervention. SR-TIGET was one of the pioneer institute bringing hematopoietic stem / progenitor cell (HSPC) gene therapy (GT) from preclinical studies to successful clinical applications in adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) and Wiskott-Aldrich syndrome (WAS).

This group is working towards the identification of the genetic bases and the pathophysiological processes underlying PIDs and autoimmune/autoinflammatory diseases with the goal of developing novel ex vivo gene and cell therapy strategies for such conditions.

Research activity

In addition to ADA-SCID and WAS, the research group is currently investigating the molecular and cellular mechanisms linked to mutations in genes encoding the gp91phox NADPH oxidase (Chronic Granulomatous Disease), ARPC1B and ADA2/CECR1 with the final goal to develop a gene therapy approach for these diseases.

Moreover, researchers are characterizing the biological properties of HSPCs and mesenchymal stromal cells (MSCs) and improving the procedures for their ex vivo isolation, genetic modification and transplantation. Specifically, the group is conducting vector integration studies using HSPCs isolated from PID patients undergoing gene therapy. These studies will provide crucial information on vector biology, dynamics of gene-corrected HSPCs and safety of retroviral/lentiviral-mediated gene therapy. The unit is also exploring the possibility to use HSPCs in combination with MSC to improve the outcome of HSPC-gene therapy strategies. Collectively, these studies will contribute to advance our knowledge on PIDs and improve patients’ care.