Gene transfer into the hematopoietic system.

Efficient transfer of heterologous genes into long-term reconstituting stem cells remains difficult to achieve in large animal models and humans. Long-term expression of introduced gene sequences in hematopoietic cells after gene transfer and bone marrow transplantation procedures is usually seen in less than 5% of cells. Retroviral vectors remain the standard tool for this technology, but these vectors have distinct disadvantages, such as the requirement for cycling target cells, random integration into the infected cell genome, and problems with long-term gene expression in long-term reconstituting stem cells. Novel retroviral vectors and producer cell lines that may address some of these problems have been constructed. In addition, modifications of the retroviral infection protocol and the use of alternative stem cell sources such as cord blood or mobilized peripheral blood cells have been tested with some promise. Recent data suggest that adeno-associated virus-based vector might prove an alternative to retroviral vectors in some cases.