This technology includes lentivirus vectors to be used to treat sickle cell disease and beta thalassemia. (i) Lin28A or Lin28B vectors designed for erythroid-specific expression using EKLF1, SPTA1, or similar erythroid-specific regulatory elements will be used to transduce hematopoietic stem cells isolated from humans with sickle cell disease or beta-thalassemia syndromes. (ii) Lentiviral vectors or other means of delivery for tough decoy inhibitors or other means of reducing the expression of the most critical Let-7 mRNA will be used to transduce hematopoietic stem cells isolated from humans with sickle cell disease or beta-thalassemia syndromes. Cells that have received the genetic modifications can be reinfused into the same patient (autologous transfusion), after which they home to the bone marrow and persist. These vectors will also be combined with other drugs or approaches to modify or increase globin gene or protein expression via alternate mechanisms in order to achieve additive or synergistic effects.