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

✍ Scribed by Eun Young Kim; Young Bin Hong; Zhennan Lai; Youl-Hee Cho; Roscoe O. Brady; Sung-Chul Jung

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 249 KB
• Volume: 7
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.732

✦ Synopsis

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. Copyright © 2005 John Wiley & Sons, Ltd.