LONG-TERM EXPRESSION OF THE GLUCOCEREBROSIDASE GENE IN MOUSE AND HUMAN HEMATOPOIETIC PROGENITORS

Gaucher disease (GD), one of the most common inherited metabolic disor ders, is an excellent candidate for gene therapy using hematopoietic s tem cells as targets. Animal models have demonstrated the feasibility of introducing the human glucocerebrosidase (GC) gene into hematopoiet ic progenitors with long term expression using a variety of retroviral vectors. We have previously demonstrated the expression and integrati on of the human GC gene in mouse hematopoietic progenitors end their p rogeny 4-8 months post transplant in primary recipients using the retr oviral vector MFG-GC. We now demonstrate enzyme expression in peripher al blood lymphocytes of secondary recipients more than 12 months post transplantation. We also show a transduction efficiency of up to 95% i n colony forming unit-granulocyte macrophage (CFU-GM) colonies generat ed from transduced CD34+ cells from a variety of sources, using a cent rifugation promoted infection protocol. Transduction has also been doc umented in long term culture initiating cells (LTCIC) from the same tr ansduced CD34+ cells. These data indicate efficient transduction of mo use hematopoietic progenitors as well as human CD34+ cells using the r etroviral vector MFG-GC.