Osteoblast ablation burns out functional stem cells

robust, and simplified enough to be acceptable for clinical development. 5,6 This is where the fact that the academia-industry interface has been present in this work since its inception can prove extremely useful. Second, this iterative process will benefit from the methodological advances of others, for example, recent use of ZFNs for integration of corrective DNA into the interleukin 2 receptor g gene in HSCs from an individual with X-linked severe combined immunodeficiency. 7 Third, gene therapy technology needs to be developed simultaneously with protocols to sustain and maintain autologous HSCs through the collection and transgenesis steps and with a clinical transplantation trial to mediate their significant and permanent engraftment. 8 Hematopoietic cell transplantation (HCT) was the first gene therapy. 9 It has been used as a life-saving measure for multiple genetic disorders (in some individuals with SCA, for example, or in mucopolysaccharidosis type I, Fanconi anemia, dyskeratosis congenita, genetic forms of immune deficiencies, adrenoleukodystrophy, epidermolysis bullosa, etc). Viral-mediated gene therapy is already in clinical trials (or in preclinical development) for a majority of them. Gene editing has the potential to be the next conceptual step in gene therapy. Critically, even partial gene correction is likely to be clinically meaningful, as SCA heterozygotes are typically free of disease symptoms, and recipients of HCT with mixed chimerism can derive significant clinical benefits from as little as one-fifth donor hematopoietic cells.