Selective Amplifier Gene (SAG)

SAG is a system of artificial genes that improves the effect of gene transfer by vectors. It is useful in introducing genes into blood cells for the treatment of hematological and other disorders. It was originally developed as a tool for the “Hematopoietic stem cell gene therapy,” in which a long term gene expression in patients was intended by transferring therapeutic genes into hematopoietic stem cells (progenitors of blood cells). SAG is to be carried together with a therapeutic gene by a retrovirus vector when the gene transfer efficiency by the vector is low and efficacy is not expected by the therapeutic gene alone. After gene transfer, cells carrying SAG can be stimulated to divide with extracellular stimuli such as cytokines and steroids, resulting in a rapid amplification of cells carrying the therapeutic gene. This system allows achievement of therapeutic effects by selectively amplifying the cells with the therapeutic gene even when the initial gene transfer efficiency is low and the number of transduced cells is small.

Cell multiplication of hematopoietic stem cells

In gene transfer evaluation studies using monkeys, SAG successfully increased the gene transfer efficiency of a retrovirus vector from less than 0.1% to 9% of peripheral blood cells without the use of bone marrow ablation.