Recombinant lentiviral vectors having a region encoding a functional globingene and large portions of the beta-globin locus control regions whichinclude DNase I hypersensitive sites HS2, HS3 and HS4 provides expression ofbeta-globin when introduced into a mammal, for example a human, in vivo.Optionally, the vector further includes a region encoding a dihydrofolatereductase. The vector may be used in treatment of hemoglobinopathies,including beta-thalessemia and sickle-cell disease. For example, hematopoieticprogenitor or stem cells may be transformed ex vivo and then restored to thepatient. Selection processes may be used to increase the percentage oftransformed cells in the returned population. For example, a selection markerwhich makes transformed cells more drug resistant than un-transformed cellsallows selection by treatment of the cells with the corresponding drug.
