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Production of human factor IX in animals by genetically modified skin
fibroblasts: potential therapy for hemophilia B
TD Palmer, AR Thompson and AD Miller
Department of Molecular Medicine, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
Inherited diseases might be treated by introducing normal genes into a
patient's somatic tissues to correct the genetic defects. In the case of
hemophilia resulting from a missing clotting factor, the required gene
could be introduced into any cell as long as active factor reached the
circulation. We previously showed that retroviral vectors can efficiently
transfer genes into normal skin fibroblasts and that the infected cells can
produce high levels of a therapeutic product in vitro. In the current
study, we examined the ability of skin fibroblasts to secrete active
clotting factor after infection with different retroviral vectors encoding
human clotting factor IX. Normal human fibroblasts infected with one vector
secreted greater than 3 micrograms factor IX/10(6) cells/24 h. Of this
protein, greater than 70% was structurally and functionally
indistinguishable from human factor IX derived from normal plasma. This
suggests that infected autologous fibroblasts might provide therapeutic
levels of factor IX if transplanted into patients suffering from hemophilia
B. By transplanting normal diploid fibroblasts infected with the factor IX
vectors, we showed that human factor IX can be produced and is circulated
at readily detectable levels in rats and mice.
Volume 73,
Issue 2,
pp. 438-445,
02/01/1989
Copyright © 1989 by The American Society of Hematology
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