Gene Therapy for SCID

Abstract

Severe combined immunodeficiencies (SCIDs) are a group of rare genetic diseases characterized by profound abnormalities of cellular and humoral immunity. They have been identified as ideal candidates for treatment by gene therapy and have led the development of gene therapy for other bone marrow disorders. SCID-X1 and adenosine deaminase SCID have been successfully treated with hematopoietic stem cell gene therapy (HSC-GT) and patients show impressive levels of immune reconstitution. Initial clinical trials employed γ-retroviral vectors, but leukaemia arose in five SCID-X1 patients due to insertional mutagenesis. Clinical trials using self-inactivating γ-retroviral and lentiviral vectors incorporating improved safety features are currently being conducted in Europe and North America. With safer approaches, we anticipate other SCIDs such as recombinase activating gene and Artemis deficiency will be treated with HSC-GT. Looking to the future, gene editing strategies hold enormous promise, and SCID will continue to be the paradigm condition for the development of these applications.