title: Long-term expression of the human glucocerebrosidase gene in vivo after transplantation of bone-marrow-derived cells transformed with a lentivirus vector.
abstract: 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.
authors.affiliation: Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, Seoul, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Lai
authors.forename: Youl-Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Roscoe O
authors.initials: RO
authors.lastname: Brady
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Jung
mesh_terms: 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
chemical_list: D005962:Glucosylceramidase