Book Chapter

Lentiviral Vectors for the Gene Therapy of Lympho-Hematological Disorders

Perhaps no clinical field stands to gain more from gene therapy than that of lympho-hematological disorders. First, blood cells are the site of manifestation of a large number of well-characterized monogenic hereditary defects, the correction of which would eliminate all symptoms in affected individuals (Table 1). Second, adding a genetic component to currently used drug-based approaches could facilitate the control of several acquired diseases of the immuno-hematological system including leukemia and AIDS, and could be used to provide blood precursors with an increased resistance against the toxicity of chemotherapy used in cancer treatment. Third, most of the cellular components of this tissue are renewed throughout life and derived from a single progenitor, the so-called human hematopoietic stem cell (hHSC). Fourth, not only is this common precursor currently the best characterized of all stem cells, but it is also relatively easy to isolate, it can be manipulated ex vivo, and it can be reintroduced into the body with an efficacy high enough to reconstitute a functional organ. Finally, the recently discovered plasticity of stem cells, with hematopoietic progenitors capable of contributing to the regeneration of tissues such as muscle (FERRARI et al. 1998; GUSSONI et al. 1999) or liver (LAGASSE et al. 2000), indicates that gene therapy through the modification of hHSC may open truly vertiginous therapeutic perspectives extending well beyond the lympho-hematopoietic system.


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