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

James Brauker, Gloria H. Frost, Varavani Dwarki, Tarlochan Nijjar, Richard Chin, Victoria Carr-Brendel, Carol Jasunas, Debra Hodgett, Wendy Stone, Lawrence K. Cohen, Robert C. Johnson

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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 x 107 cells, two subcutaneously, two in epididymal fat) and in mice (two 20-μl devices, each containing 2 x 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 x 106 cells), or without a device (1 x 107 cells implanted freely), either subcutaneously or in epididymal fat. The freely implanted cells expressed transiently, reaching more than 100 ng/ml in each site by day 4, but dropped to zero by day 20 (subcutaneous) or day 90 (epididymal fat). In devices, levels gradually increased to 100 ng/ml (subcutaneous) or 300 ng/ml (epididymal fat), remaining high for more than 100 days. These results show long-term, high-level expression of a human protein: (1) when cells are implanted within a cell transplantation device, but not when the cells are freely implanted, and (2) from a transgene driven by a viral promoter. An alloprotective device will enable the use of cloned cell lines that can be subjected to stringent quality control assessment that is impossible to achieve with autologous approaches.

Original languageEnglish (US)
Pages (from-to)879-888
Number of pages10
JournalHuman Gene Therapy
Issue number6
StatePublished - Apr 10 1998
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics


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