Delivery of human factor IX in mice by encapsulated recombinant myoblasts:
a novel approach towards allogeneic gene therapy of hemophilia B
G Hortelano, A Al-Hendy, FA Ofosu and PL Chang
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
A potentially cost-effective strategy for gene therapy of hemophilia B is
to create universal factor IX-secreting cell lines suitable for
implantation into different patients. To avoid graft rejection, the
implanted cells are enclosed in alginate-polylysine-alginate microcapsules
that are permeable to factor IX diffusion, but impermeable to the hosts'
immune mediators. This nonautologous approach was assessed by implanting
encapsulated mouse myoblasts secreting human factor IX into allogeneic
mice. Human factor IX was detected in the mouse plasma for up to 14 days
maximally at approximately 4 ng/mL. Antibodies to human factor IX were
detected after 3 weeks at escalating levels, which were sustained
throughout the entire experiment (213 days). The antibodies accelerated the
clearance of human factor IX from the circulation of the implanted mice and
inhibited the detection of human factor IX in the mice plasma in vitro. The
encapsulated myoblasts retrieved periodically from the implanted mice up to
213 days postimplantation were viable and continued to secrete human factor
IX ex vivo at undiminished rates, hence suggesting continued factor IX gene
expression in vivo. Thus, this allogeneic gene therapy strategy represents
a potentially feasible alternative to autologous approaches for the
treatment of hemophilia B.
Volume 87,
Issue 12,
pp. 5095-5103,
06/15/1996
Copyright © 1996 by The American Society of Hematology
