chapter  8
Reconstitution of the Myeloid and Lymphoid Compartments after the Transplantation of Autologous and Genetically Modied CD34+ Bone Marrow Cells, Following Gamma Irradiation in Cynomolgus Macaques
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Background Gene therapy strategies hold promise for the treatment of hematopoietic disorders. All hematopoietic lineages, including polymorphonuclear cells, monocytes, lymphocytes and natural killer cells, and hematopoietic stem cells (HSC) – which are capable of self-renewal and pluripotent dierentiation – have been targeted for transduction with therapeutic genes. Most diseases for which gene therapy could be proposed require stable and long-lasting transgene expression for e- cacy. Retroviral vectors present the major advantage of integrating the transferred DNA stably into the genome of target cells, which is then passed on to progeny. However, they cannot infect and integrate into non dividing cells [1]. Most HSC are quiescent [2], respond slowly to stimulation [3-7] and tend to dierentiate and lose their repopulating capacity upon stimulation [3,8-11]. Lentiviral vectors can be used to transduce cells in growth arrest [12] in vivo and ex vivo[13], thanks to interaction of the preintegration complex – composed of viral VPX and integrase proteins – with the nuclear pore complex[14]. Vectors derived from

HIV-1[15,16], HIV-2[17], FIV[18] and equine infectious anemia virus (EIAV) have been tested[19].