Lastly, we show that this targeting strategy can be used for transfer of a therapeutic gene into CD34(+) cells obtained from patients suffering of X-linked chronic granulomatous disease.
These findings were recapitulated in human neutrophils derived from transduced X-CGDCD34(+) cells in vivo, and suggest that the chimeric promoter will have utility for gene therapy of myeloid lineage disorders such as CGD.
In the current study we demonstrate that the same vector (MFGS-gp91phox) pseudo-typed with RD114 envelope in a 4-day culture/transduction regimen results in a 7-fold increase in correction of NOD/SCID mouse repopulating X-CGDCD34+ PBSCs (14%-22% corrected human neutrophils; human cell engraftment 13%-67%).
Finally, Nox1 partially restores superoxide production in neutrophils differentiating ex vivo from gp91(phox)-deficient CD34(+) peripheral blood-derived stem cells derived from patients with X-linked chronic granulomatous disease.
Under the latter conditions, lentivector and MFGS achieved significant ex vivo correction of X-CGDCD34(+)PBSCs (18% and 54% of cells expressing gp91(phox), associated with 53% and 163% of normal superoxide production, respectively).