Production of recombinant human protein C in vitro and in vivo by muscle cells.
Protein C plays a key role in a natural anticoagulation mechanism, and is also implicated in fibrinolytic and anti-inflammatory functions. Here we describe the production of biologically active human protein C by muscle-targeted gene transfer. Human protein C expression vectors were designed and constructed to produce human protein C in skeletal muscle cells. These vectors were tested in transient and stable transfections of SCID mice myoblasts. Stably transfected cells produced as high as 2.27 microg/10(6) cells/day. Human protein C produced had a relative activity of 92+/-8% compared to the plasma derived human protein C, and was composed of alpha and beta forms, 69% and 31%, respectively. After implantation of stably transfected myoblasts into the hind limb muscles of SCID mice, systemic stable production of human protein C in a range of 31-116 ng/ml serum was obtained up to at least 2.5 months.
Türkay
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Department of Human Genetics, The University of Michigan Medical School, Ann Arbor 48109, USA.
Wang
J M
JM
Kurachi
K
K
D000818:Animals; D001777:Blood Coagulation; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000378:metabolism*; D011486:Protein C / Q000096:biosynthesis* / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
D011486:Protein C; D011994:Recombinant Proteins