Control of stem cell proliferation and differentiation to achieve stable gene transfer and expression.

Although the hematopoietic stem cell (HSC) seems to be a convenient target for gene therapy, data from human clinical trials have so far shown low levels of gene transduction. The new model of human stem cells, immunodeficient mice repopulating cells (SRC), has similarly demonstrated that SRC were rarely transduced by protocols used in past studies. Cytokines such as stem cell factor and interleukin-3, used so far to obtain cell proliferation in transduction protocols, might induce HSC to differentiate and impair their repopulating potential. In this scenario, there is a need for new gene transfer protocols associated with minimal cell differentiation and stable expression of the transduced gene in the majority of mature cells generated from transduced HSC.