How Primary Immunodeficiencies Have Made Gene Therapy a Reality

Abstract Over the last 25 years, identification of the causal genes for many primary immunodeficiencies (PIDs) has made gene therapy – the introduction of foreign DNA into cells – a true therapeutic option. Concomitant advances in the development of retroviral vectors and the manipulation of hematopoietic progenitor cells have progressively turned gene therapy into a feasible approach. The first clinical successes, achieved in two severe combined immunodeficiencies, X-linked severe combined immunodeficiency and adenosine deaminase deficiency, relied on the selective growth advantage conferred by transgene expression. The occurrence of genotoxic events associated with the use of first-generation vectors has prompted researchers to develop safer vectors, which are now being used to treat an ever-increasing number of PIDs.