Over-expression of factor VIIa in vivo.
Although recombinant factor VIIa has been shown to bypass the deficiency in factor VIII or factor IX, efforts to reduce factor consumption and subsequently treatment cost have been focused on continuous infusion regimens with variable success. Using an engineered factor VII that can be secreted as factor VIIa, viral-mediated delivery of this transgene in the mouse liver resulted in phenotypic correction of murine hemophilia B, at expression levels of approximately 1 microg/ml. This model of factor VIIa continuous infusion can be further used to address the potential risk of thrombosis, in a transgenic model approach. The relative contribution of the extrinsic and/or intrinsic pathways in such risk can be dissected by crossing over-expressing FVIIa mice to recently described models of low expression of tissue factor or factor X. Our current data support the potential of factor VIIa gene transfer as a therapeutic alternative to bolus dosing but effective monitoring and modulation of factor VIIa expression will most likely be required.
Margaritis
Paris
P
The Children's Hospital of Philadelphia, Division of Hematology, Philadelphia, PA, USA. margaritis@email.chop.edu
D000818:Animals; D015942:Factor VIIa / Q000009:adverse effects / Q000235:genetics* / Q000378:metabolism*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D051379:Mice; D008822:Mice, Transgenic
D015942:Factor VIIa