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Primary skin fibroblasts from hemophilic dogs were transduced by recombinant retrovirus (LNCdF9L) containing a canine factor IX cDNA. High levels of biologically active canine factor IX (1.0 micrograms per 10(6) cells per 24 hr) were secreted in the medium. The level of factor IX produced increased substantially if the cells were stimulated by basic fibroblast growth factor during infection. Additionally, we also report that endothelial cells transduced by this virus can produce high levels of biologically active factor IX. We propose that skin fibroblasts and endothelial cells from hemophilia B dogs may serve as potential venues for the development and testing of models for treatment of hemophilia B by retrovirally mediated gene replacement therapy.

Phenotypic correction of factor IX deficiency in skin fibroblasts of hemophilic dogs.