This review describes the main steps which led to carrying out the gene ther-apy clinical trial for Xlinked severe combined immune deficiency (SCID-X1) patients, from the preparation of the retroviral vector up to the design of GMP conditions to transduce ex vivo the CD34+cells of patients. This gene therapy protocol is currently being applied and the encouraging preliminary results published (1 ). The success of this protocol could be mainly attributed to the physiopathology of the SCID-X1 disease (for review, see ref. 2 ), which is a good model for a gene therapy application. However, progress in the technology of gene transfer into hematopoietic progenitor cells (HPCs) may also have contributed to this success. The most important improvement concerns the use of fibronectin, which increases the transduction efficiency by colocalization of the retroviral particles and the HPC. The other improvement is related to the use of the early-acting cytokines such as stem cell factor (SCF), Flt3 ligand, and megakaryocyte growth and differentiation factor (M-GDF), which promote immature CD34+ CD38low cycle induction, making them permissive for transgene integration with minimal loss of their lymphoid potential (3 )