Cerebral ischaemic stroke is the leading cause of disability and the third leading cause of mortality in the world. Currently, intravenous administration of recombinant tissue-type plasminogen activator (tPA), a fibrinolytic serine protease, is the only pharmacological treatment of cerebral ischaemic stroke approved by the European Medicines Agency and the American Food and Drug Administration. However, several lines of evidence implicate circulating tPA in detrimental effects, including neurotoxicity and haemorrhagic transformation, especially in an ischaemic context. The low-density lipoprotein receptor related protein-1 (LRP-1) is a central mediator of the adverse effects ascribed to tPA.

During his PhD studies, Nils Bjerregaard has characterised structured synthetic RNA ligands (“aptamers”) to tPA capable of inhibiting the interaction of tPA with LRP-1 while minimally affecting the crucial fibrinolytic properties of the protease. These aptamers may improve the safety and efficacy of fibrinolytic therapy with tPA. A conjugate construct combining two different aptamers in a single molecule possessed activity two orders of magnitude higher than each constituent aptamer, and was an efficient inhibitor of fibrinolysis with potential applications in the treatment of bleeding disorders or the management of bleeding during surgical procedures.

The PhD degree was completed at the Department of Molecular Biology, Faculty of Science and Technology, Aarhus University.

This résumé is prepared by the PhD student.

Time: Wednesday 9 December 2015 at 13.00
Place: Building 1252. Room 204, The Lakeside Auditoriums, Eduard Biermann Auditorium, Bartholins Allé 3, 8000 Aarhus C
Title of dissertation: tPA-binding RNA Aptamers
Contact information: Nils Bjerregaard, e-mail: nilsbj@mbg.au.dk, tel.: +45 60 64 70 98
Members of the assessment committee:
Professor, Vittorio de Franciscis, Istituto per l’Endocrinologi ae l’Oncologia Sperimentale “G. Salvatore”
Professor, Michael Toft Overgaard, Department of Chemistry and Bioscience - Section for Biotechnology, Aalborg University
Professor, Claus Oxvig (Chair), Department of Molecular Biology and Genetics, Aarhus University, Denmark
Main supervisor:
Professor Peter A. Andreasen, Department of Molecular Biology and Genetics, Aarhus University, Denmark
Co-supervisor:
Daniel M. Dupont, Department of Molecular Biology and Genetics, Aarhus University, Denmark
Language: The PhD dissertation will be defended in English.

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1520, room 128-134, 8000 Aarhus C.

echnology/GSST, Ny Munkegade 120, bygning 1520, lokale 128-134, 8000 Aarhus C.