Abstract
Factor IX (Christmas factor), a vitamin K-dependent plasma protein made in the liver, functions in the middle phase of the intrinsic pathway of blood coagulation1. A functional deficiency of factor IX underlies haemophilia B, a chromosome X-linked recessive disease for which the major therapeutic approach is replacement treatment using factor IX concentrates. The cloning and characterization of the gene for human factor IX2–4 would mean that human factor IX could be produced in greater yield and purity through using recombinant DNA techniques5. We have now used a human factor IX cDNA clone4, inserted into a vaccinia virus-derived vector, to infect human hepatoma cells which normally produce no factor IX6, and mouse fibroblasts. Fully active factor IX was produced by the hepatoma cells, whereas the fibroblasts produced a protein less active than natural factor IX, even in the presence of high levels of vitamin K. Human factor IX is extensively post-translationally modified, and thus represents probably the most complex protein produced in active form by recombinant DNA techniques to date. Our study also illustrates the potential of vaccinia virus-based vectors for expressing significant amounts of complex, clinically useful proteins in eukaryotic cells, in addition to its already demonstrated usefulness for producing live recombinant vaccines7–9.
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de la Salle, H., Altenburger, W., Elkaim, R. et al. Active γ-carboxylated human factor IX expressed using recombinant DNA techniques. Nature 316, 268–270 (1985). https://doi.org/10.1038/316268a0
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DOI: https://doi.org/10.1038/316268a0
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