A new direction for gene therapy: intrathymic T cell–specific lentiviral gene transfer
J. Clin. Invest. Ruth Seggewiss, et al. 115:2064 doi:10.1172/JCI26041 [Go to this article.]

Figure 1
Gene therapy approaches for SCID. (A) Previously (4, 5), after informed parental consent, bone marrow was obtained from young boys with SCID-X1 who did not have an HLA-identical donor. Selection for the CD34⁺ cell population was performed, and these cells were stimulated to grow in media containing 4% fetal calf serum and supplemented with SCF, IL-3, Flt-3 ligand (FLT-3L), and megakaryocyte growth and differentiation factor (MGDF). The cells were transduced with a Moloney leukemia virus_based (MLV-based) replication-incompetent vector containing the common γ chain (γc) for 3 days. The cells were reinfused into the patients without a preparative conditioning regimen. In the majority of the boys, mature and functional T cells were reconstituted. Unfortunately, 3 of 11 boys enrolled in this clinical trial developed a T cell leukemia related to the oncoretroviral vector used (6). (B) In this issue of the JCI, Adjali and colleagues report (10) that they injected a T cell_specific lentiviral vector encoding human ZAP-70 and enhanced GFP (eGFP) directly into the thymi of 8- to 12-week old ZAP-70^–/– mice after thoracic surgery. Some of the mice partially reconstituted mature and functional T cells. LTR, long terminal repeat; LTR-SIN, self-inactivating LTR.