Grant: Team Grant: E-Rare Joint Transnational Call

In this research proposal, we will explore the potential of rebalancing hemostasis in hemophiliacs through the use of small fragments of antibodies generated to anticoagulant components of the blood clotting system. These so called nanobodies are 1/10 the size of regular antibodies and possess a number of production and biological advantages while maintaining the specificity of antibodies. We will develop a series of nanobodies to the natural anticoagulant proteins, antithrombin and protein S. These products will initially be evaluated for their potential to enhance clotting through a range of in vitro tests and will subsequently be tested in mouse and dog models of hemophilia. In addition to studying the benefit of nanobody protein-based therapy, we will also assess the potential of a gene therapy protocol in which long-term production of the nanobodies will be mediated by a viral vector delivery system.