Sustained expression of high levels of human factor IX from human cells implanted within an immunoisolation device into athymic rodents.

ABSTRACT Immunoisolation of allogeneic cells within a membrane-bound device is a unique approach for gene therapy. We employed an immunoisolation device that protects allograft, but not xenograft, cells from destruction, to implant a human fibroblast line (MSU 1.2) in athymic rodents. Cells, transduced with the MFG-human factor IX retroviral vector, and expressing 0.9 μg/106 cells/day in vitro, were implanted in rats (four 40-μl devices, each containing 2 × 107 cells, two subcutaneously, two in epididymal fat) and in mice (two 20-μl devices, each containing 2 × 106 cells, subcutaneously). Plasma factor IX levels increased for 50 days, reaching maxima of 203 ng/ml (rat) and 597 ng/ml (mouse), and both continued at greater than 100 ng/ml for more than 140 days. A clone derived from the transduced cells, making 5 μg of factor IX/106 cells/day, was implanted within a device (one 20-μl device containing 2.5 × 106 cells), or without a device (1 × 107 cells implanted freely), either subcutaneously or in epididym...