Methods for efficient retrovirus-mediated gene transfer to mouse hematopoietic stem cells

A variety of genetic and acquired diseases could conceivably be treated by gene therapy targeted to hematopoietic stem cells (HSC). Inevitably, the effort to develop reliable methods of gene transfer into stem cells has raised many questions about their biology and role in the development and maintenance of hematopoiesis. As a result, we currently have a convergence of research goals in the areas of stem cell biology and gene therapy. Murine models for stem cell transduction have played a useful role in establishing two basic principles: retroviral vectors can transduce pluripotent self-renewing hematopoietic stem cells and retroviral vectors can express foreign gene products in the differentiated progeny of stem cells. Murine models also have allowed the identification of several key factors that allow efficient transduction of stem cells and each of these is dealt with here. However, methods for stem cell transduction that are effective with mouse cells have only been partially successful in dog, nonhuman primate, and human models. Whereas scale-up of stem cell transduction procedures for human applications will present unique technical problems, mouse models may yet provide further insight into the mechanisms of efficient stem cell gene transfer that can then be used to design enhanced and reproducible protocols.