PRODUCTION OF HUMAN FACTOR-IX IN ANIMALS BY GENETICALLY MODIFIED SKIN FIBROBLASTS - POTENTIAL THERAPY FOR HEMOPHILIA-B

  • 1 February 1989
    • journal article
    • research article
    • Vol. 73  (2) , 438-445
Abstract
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 retrovial 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 > 3 .mu.g factor IX/106 cells/24 h. Of this protein, > 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.