Development of novel therapeutic approaches for primary immunodeficiency.

A single faulty gene can leave a child’s immune system unable to fight off even a mild infection, and this project aims to fix that at the genetic level. The research tackles two linked problems in primary immunodeficiency, a group of inherited disorders where the immune system is missing key parts. Current gene therapy can introduce new mutations or fail to work in the right tissues. The team will design safer gene-transfer vectors that are less likely to cause cancer and more precisely active in blood cells. They will also develop gene-correction strategies using reprogrammed cells from the patient’s own body. Separately, they will study the Wiskott-Aldrich Syndrome protein (WASp), which when mutated causes a severe combined immunodeficiency. By examining how mutant forms of WASp disrupt cell division, immune synapse formation, and dendritic cell trafficking in mice, they aim to understand why the immune system fails. If successful, the work could produce safer, more effective gene therapies for several rare immune diseases. The fundamental studies on WASp may also reveal general principles of how immune cells organise themselves to attack pathogens, with potential relevance to autoimmune conditions or vaccine design.