title: The future of recombinant coagulation factors.
abstract: Hemophilias A and B are X chromosome-linked bleeding disorders, which are mainly treated by repeated infusions of factor (F)VIII or FIX, respectively. In the present review, we specify the limitations in expression of recombinant (r)FVIII and summarize the bioengineering strategies that are currently being explored for constructing novel rFVIII molecules characterized by high efficiency expression and improved functional properties. We present the strategy to prolong FVIII lifetime by disrupting FVIII interaction with its clearance receptors and demonstrate how construction of human-porcine FVIII hybrid molecules can reduce their reactivity towards inhibitory antibodies. While the progress in improving rFIX is impeded by low recovery rates, the authors are optimistic that the efforts of basic science may ultimately lead to higher efficiency of replacement therapy of both hemophilias A and B.
authors.affiliation: Department of Biochemistry, Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, MD 20855, USA. saenko@usa.redcross.org
authors.forename: E L
authors.initials: EL
authors.lastname: Saenko
authors.forename: N M
authors.initials: NM
authors.lastname: Ananyeva
authors.forename: M
authors.initials: M
authors.lastname: Shima
authors.forename: C A E
authors.initials: CA
authors.lastname: Hauser
authors.forename: S W
authors.initials: SW
authors.lastname: Pipe
mesh_terms: D005164:Factor IX / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005169:Factor VIII / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy; D006801:Humans; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D011994:Recombinant Proteins; D005169:Factor VIII; D005164:Factor IX