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

Eun Young Kim, Young Bin Hong, Zhennan Lai, Youl Hee Cho, Roscoe O. Brady, Sung Chul Jung

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish
Pages (from-to)878-887
Number of pages10
JournalJournal of Gene Medicine
Volume7
Issue number7
DOIs
StatePublished - Jul 2005

Keywords

  • Gaucher disease
  • Glucocerebrosidase
  • Hematopoietic stem cell
  • Lentivirus
  • Transplantation

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