Blood, 1 August 2001, Vol. 98, No. 3, pp. 504-504
Foamy virus vectors: new armaments for hematopoietic cell gene
therapy
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.
Brian P. Sorrentino
University of Washington
