The first gene therapy clinical trials involved the ex vivo retroviral delivery of a therapeutic adenosine deaminase (ADA) transgene to T cells to treat children with severe combined immunodeficiency (ADA-SCID),256 and later the treatment of X-linked SCID (X-SCID) by retroviral gene delivery to CD34+ hematopoietic stem cells (HSCs).257 This early focus on ex vivo gene therapy for immunodeficiency was based on the desperate need to develop treatment for these otherwise fatal disorders as well as the availability of methods for efficient retroviral gene delivery to cells in culture. This evidence concerns the gene ADA and T-B+ severe combined immunodeficiency due to gamma chain deficiency.