The three studies -- reported by researchers from the National Center for Tumor Diseases, Heidelberg, Germany; University College London, London, United Kingdom; and the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy -- indicate that the retroviruses used to deliver the genes of interest in these studies, gammaretroviruses, integrated near the 5" ends of genes that are active in the treated cell population. Although the diversity of the detected retroviral integration sites decreased following transplantation into patients because the treated cells differentiated, the sites detected remained at the 5" end of genes active in the cell populations analyzed. Importantly, the retrovirus integration sites observed in cells from successfully treated patients were not significantly different from those observed in cells from patients that went on to develop leukemia-like disease. As discussed in the accompanying commentary by Frederic Bushman from the University of Pennsylvania, Philadelphia, these studies are critical if researchers are to determine whether the dangers of retroviral gene therapy can be predicted and/or eliminated.
TITLE: Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy
Christof von Kalle
National Center for Tumor Diseases, Heidelberg, Germany.
Phone: 49-6221-56-6990; Fax: 49-6221-56-6967; E-mail:
Contact: Karen Honey
Journal of Clinical Investigation