Novel approaches and mechanisms in hematopoietic stem cell gene therapy

Hematopoietic stem cell gene therapy is one of the most exciting clinical tools to emerge from the gene therapy stable. This technology combines the expansion capability of hematopoietic stem cells, capable of replacing the entire blood and immune system of an individual, with the capacity for long-term replacement of one or more gene copies using integrating gene therapy vectors. Hematopoietic stem cell gene therapy benefits significantly from the pre-existing experience of standard blood and marrow transplantation, whilst at the same time having the capacity to deliver a safer and more effective therapy to a wider range of diseases. In this review we summarize the potential of hematopoietic stem cell gene therapy to expand the scope of hematopoietic stem cell transplantation, including the evolution of vector delivery systems and the success and failures of current clinical experience with this treatment. In particular we deal with the incidence of vector mediated transformation in patients and the steps that have been taken to minimize this risk. Finally we discuss the innovations in preclinical development that are likely to drive the future of this field, including the expansion to many more genetic diseases, particularly those affecting the brain. © Discovery Medicine.