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 three-fold 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.
Kim
Eun Young
EY
Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, Seoul, Korea.
Hong
Young Bin
YB
Lai
Zhennan
Z
Cho
Youl-Hee
YH
Brady
Roscoe O
RO
Jung
Sung-Chul
SC
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D005776:Gaucher Disease / Q000235:genetics / Q000628:therapy; D005822:Genetic Vectors; D005962:Glucosylceramidase / Q000235:genetics* / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014018:Tissue Distribution; D014161:Transduction, Genetic
D005962:Glucosylceramidase