Design of safer retroviral vectors. (A) A strategy has been developed for recreating an insertion in the LMO2 gene that occurred in one of the patients who developed leukemia in the X-SCID trial.⁷⁹  The experimental system is a human lymphoid cell line (Jurkat) in which the LMO2 gene is not expressed.¹⁰⁰  When a conventional oncoretroviral vector having 2 intact long-terminal repeats (LTRs) is present in the intron of LMO2, its 2 promoters are strongly activated, leading to accumulation of LMO2 mRNA and protein. (B) Modification of the vector design to use an internal cellular promoter results in a weaker activation signal, which can be blocked by a chromatin insulator thereby preventing LMO2 activation.