T-LGLL: variety is the spice of this leukemia

leads to effective reconstitution of gp91 phox expression, and NADPH oxidase in vitro and in vivo protects X-CGD mice from experimental Burkholderia cepacia infection, thereby providing a preclinical proof of concept.Although in some in vitro studies gp91 phox reached levels higher than normal, the transgene was expressed at physiological levels across all lineages when transduced X-CGD patient cells were engrafted into immunodeficient mice.The lentiviral vector designed by Wong et al was compared with a myeloidspecific chimeric promoter currently in clinical trial 7 but not with other regulated vectors.The overall improvement over the chimeric myeloid promoter-based vector is considerable in that the expression pattern of endogenous gp91 phox is well recapitulated in myeloid and B cells, managing to increase expression levels without compromising expression specificity.Emerging technologies based on gene-correction approaches by homology-directed repair into the CYBB locus 10 could, in principle, provide a more robust physiological regulation vs regulated lentiviral vectors but the efficiency and long-term safety of gene editing is still under investigation.Overall, the strategy developed by Wong et al holds promise as an improved gene therapy platform for X-CGD, if further testing confirms the results obtained so far.