Atypical X-Linked Severe Combined Immunodeficiency Due to Possible Spontaneous Reversion of the Genetic Defect in T Cells

Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes

“…Unlike X-SCID and ADA-deficient SCID where there is an in vivo selective advantage for corrected cells, 57,58 there is no evidence of in vivo selection in disorders like the hemoglobinopathies or chronic granulomatous disease. Gene therapy for these disorders will require a higher level of transduction than is currently available with vectors pseudotyped with GaLV or amphotropic envelopes.…”

Selective growth advantage of wild-type lymphocytes in X-linked SCID recipients

“…Reportedly, a reversal event in the mutated ␥c gene resulted in a functional lymphoid precursor generating at least 1000 T cell clones, and the disease phenotype being significantly ameliorated. 12,13 Besides the engrafting potential of the donor cells, one should consider the immunogenicity of the donor cells and the host's immune status in BMT experiments. Although the chimerism was low, we observed that WT BM-derived granulocytes and monocytes engrafted better in X-SCID recipients than in WT animals ( Figure 3).…”

Successes and risks of gene therapy in primary immunodeficiencies

“…There is a natural selective advantage for cells expressing cc, demonstrated by skewed X chromosome inactivation in lymphocytes from female carriers 42 and a spontaneous reversion of a mutation associated with clinical improvement. 43 In preclinical studies retroviral transduction of IL2RG to Bcell lines from patients with XSCID restored normal cc expression and signaling in response to IL-2 and IL-4. [44][45][46] Gene transfer of IL2RG to HSCs from mice with XSCID restored normal immune function.…”