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Research Article Free access | 10.1172/JCI119604

Replacing the first epidermal growth factor-like domain of factor IX with that of factor VII enhances activity in vitro and in canine hemophilia B.

J Y Chang, D M Monroe, D W Stafford, K M Brinkhous, and H R Roberts

Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7035, USA. jychang@med.unc.edu

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Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7035, USA. jychang@med.unc.edu

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Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7035, USA. jychang@med.unc.edu

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Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7035, USA. jychang@med.unc.edu

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Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7035, USA. jychang@med.unc.edu

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Published August 15, 1997 - More info

Published in Volume 100, Issue 4 on August 15, 1997
J Clin Invest. 1997;100(4):886–892. https://doi.org/10.1172/JCI119604.
© 1997 The American Society for Clinical Investigation
Published August 15, 1997 - Version history
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Abstract

Using the techniques of molecular biology, we made a chimeric Factor IX by replacing the first epidermal growth factor-like domain with that of Factor VII. The resulting recombinant chimeric molecule, Factor IXVIIEGF1, had at least a twofold increase in functional activity in the one-stage clotting assay when compared to recombinant wild-type Factor IX. The increased activity was not due to contamination with activated Factor IX, nor was it due to an increased rate of activation by Factor VIIa-tissue factor or by Factor XIa. Rather, the increased activity was due to a higher affinity of Factor IXVIIEGF1 for Factor VIIIa with a Kd for Factor VIIIa about one order of magnitude lower than that of recombinant wild-type Factor IXa. In addition, results from animal studies show that this chimeric Factor IX, when infused into a dog with hemophilia B, exhibits a greater than threefold increase in clotting activity, and has a biological half-life equivalent to recombinant wild-type Factor IX.

Version history
  • Version 1 (August 15, 1997): No description
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