Promising strategies for megakaryocyte gene transfer. Displayed is a schematic diagram that summarizes 3 strategies currently being examined for megakaryocyte modification including: transplantation of cytokine-mobilized CD34⁺ PBSCs transduced with a lentiviral vector; direct injection of lentiviral vector into the bone marrow space to transduce HSCs; and lentiviral vector transduction of iPSCs dedifferentiated from peripheral blood mononuclear cells followed by transfusion of genetically altered platelets into the patient. Although each method focuses on modification of the HSCs with a lentiviral vector under the transcriptional control of a megakaryocyte-specific gene promoter, there is significant contrast in procuring the HSC target cell as well as different strategies for accomplishing megakaryocyte manipulation. HSC differentiation along the megakaryocyte lineage is depicted by stage from HSCs within the bone marrow to formation of proplatelets, preplatelets, and finally mature platelets within the vascular space. The cartoon person illustrates the routes of collection and transfusion of genetically modified cells and a potential point of injection for LV within the bone marrow space. PBSCs are all HSCs. BM, bone marrow; LV, lentivector.