Transfer of therapeutic genes into reconstituting hematopoietic stem cells offers many theoretical advantages for treating blood disorders. Recent data showing that this approach can be curative in animal models, together with promising clinical results using gene therapy in XSCID patients, have increased enthusiasm for the gene therapy approach. Despite these advances, the relative refractoriness of human hematopoietic stem cells to clinically available vector systems remains a significant obstacle for most applications. Much work has focused on development of newer vector systems that may overcome the known obstacles to stem cell transduction, such as the ability to transduce nondividing cells and utilization of appropriate virus receptors for gaining access into primitive repopulating cells.
Vassilopoulos and colleagues (page 604) describe a new vector system based on foamy viruses from the spumavirus family. Natural foamy viruses are nonpathogenic in mammals and have not been detected in human populations, providing preliminary rationale for clinical safety. These authors have developed a system for production of replication-defective foamy virus vectors and demonstrate that these vector particles efficiently transferred a marker gene into repopulating mouse hematopoietic stem cells and into human CD34+ cells in vitro. Particularly encouraging are the high and persistent levels of marker-gene expression observed in vivo and the efficiency of gene transfer observed in human cell cultures. There is some evidence to suggest these results are due to improved transduction of quiescent cells and to the novel envelope/receptor system used for stem cell entry. Although more work will be required to prove that these foamy virus vectors will be useful for efficient human stem cell transduction, the results presented here show that this system holds great promise. It is hoped that foamy virus vectors will provide a new strategic weapon for the current gene therapy armamentarium.