Expression of the gp91^phox therapeutic gene or eGFP marker gene in human cells in vivo in NOD/SCID mice that underwent transplantation with lentivector or oncoretrovirus transduced CD34⁺PBSC.

Shown is the percentage of the high side scatter CD45⁺human cells (granulocytes) detected in engrafted NOD/SCID mouse–human chimeric marrow that express transgene (human gp91^phox for transplantation with transduced X-CGD CD34⁺PBSCs or eGFP for transplantation with transduced normal CD34⁺PBSCs [3 experiments; N = total number of mice]). Approximately 10⁷ CD34⁺PBSCs were transplanted by tail-vein injection into irradiated (325 cGy) NOD/SCID mice. Marrow was harvested at 2 to 3.5 months after transplantation. All mice analyzed for this study demonstrated 15% to 60% human cell chimerism. Experiments in which CD34⁺PBSCs were transduced with lentivector, ■; those transduced with MFGS, ▪. NOD/SCID mice also underwent transplantation with similarly cultured, but nontransduced X-CGD CD34⁺PBSCs or normal CD34⁺PBSCs (not shown here, but see Figures 7-9). There was significant human cell chimerism in the marrow of these latter groups of animals (more than 15%), but no human cells expressing gp91^phox were detected in mice that received transplants of nontransduced X-CGD CD34⁺PBSCs and no human cells expressing eGFP detected in mice that received transplants of nontransduced normal CD34⁺PBSCs. In mice engrafted with normal CD34⁺PBSCs, 70% to 85% of the high side scatter CD45⁺ human cells expressed native gp91^phox.