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Long‐term expression of the human glucocerebrosidase gene in vivo after transplantation of bone‐marrow‐derived cells transformed with a lentivirus vector
Author(s) -
Kim Eun Young,
Hong Young Bin,
Lai Zhennan,
Cho YoulHee,
Brady Roscoe O.,
Jung SungChul
Publication year - 2005
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.732
Subject(s) - lentivirus , haematopoiesis , biology , genetic enhancement , stem cell , viral vector , bone marrow , glucocerebrosidase , transplantation , cancer research , vector (molecular biology) , microbiology and biotechnology , transgene , virology , immunology , gene , recombinant dna , medicine , genetics , virus , viral disease
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. Copyright © 2005 John Wiley & Sons, Ltd.