Long-term expression of the human glucocerebrosidase gene in vivo after transplantation of bone-marrow-derived cells transformed with a lentivirus vector

Background Gaucher disease is a lysosomal storage disorder resulting from a deficiency of glucocerebrosidase (GC). Recently, lentivirus vectors have been developed for efficient gene transfer into hematopoietic stem cells (HSCs). A recombinant lentivirus vector was used to evaluate the transduction of the human GC gene into murine bone-marrow-derived HSCs and its expression in their progeny. Methods Murine HSCs were transduced with lentivirus vector (lenti-EF-GC; MOI = 10 - 100). We transplanted female wild-type C57BL/6J mice with genetically modified male HSCs via the tail vein. Results We show that intravenous transplantation of transduced HSCs has therapeutic potential. Enzyme activity was increased two- to threefold in various tissues, especially in the hematopoietic system. Numerous transplanted HSCs survived for 6 months and were shown by PCR to contain the provirus genes; the Y chromosome was identified by FISH analysis in the cells of female mouse recipients. Conclusions The recombinant lentiviral vector transduces HSCs that are capable of long-term gene expression in vivo. This approach is potentially useful for the treatment of patents with Gaucher disease and other lysosomal storage disorders. Copyright (c) 2005 John Wiley & Sons, Ltd.