Recombinant lentiviral vectors having a region encoding a functional
.beta.-globin gene; and large portions of the .beta.-globin locus control
regions which include DNase I hypersensitive sites HS2, HS3 and HS4
provides expression of .beta.-globin when introduced into a mammal, for
example a human, in vivo. Optionally, the vector further includes a
region encoding a dihydrofolate reductase. The vector may be used in
treatment of hemoglobinopathies, including .beta.-thalessemia and
sickle-cell disease. For example, hematopoietic progenitor or stem cells
may be transformed ex vivo and then restored to the patient. Selection
processes may be used to increase the percentage of transformed cells in
the returned population. For example, a selection marker which makes
transformed cells more drug resistant than un-transformed cells allows
selection by treatment of the cells with the corresponding drug.