Production of Recombinant Human Protein C In Vitro and In Vivo by Muscle Cells

Ataç Türkay; Jian-Min Wang; Kotoku Kurachi

doi:10.1055/s-0037-1614562

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 81(05): 727-732
DOI: 10.1055/s-0037-1614562

Rapid Communication

Schattauer GmbH

Production of Recombinant Human Protein C In Vitro and In Vivo by Muscle Cells

Ataç Türkay

¹From the Departments of Human Genetics The University of Michigan Medical School, Ann Arbor, Michigan

²Internal Medicine, The University of Michigan Medical School, Ann Arbor, Michigan

³Wayne State University School of Medicine, Department of Internal Medicine, Detroit, MI, USA

,

Jian-Min Wang

¹From the Departments of Human Genetics The University of Michigan Medical School, Ann Arbor, Michigan

,

Kotoku Kurachi

¹From the Departments of Human Genetics The University of Michigan Medical School, Ann Arbor, Michigan

› Author Affiliations

Abstract

Summary

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 μg/10⁶ 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 α and β 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.

Current address: J. Wang, Department of Hematology, Changai Hospital, 174 Changai Road, Yangpu District, Shangai 200433, China

Full Text

References

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