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Investigation of pathogenesis of TSEs using aptamers: novel analytical and diagnostic tools

Reference	BSD17731
Principal Investigator / Supervisor	Professor William James
Co-Investigators / Co-Supervisors	Dr Moira Bruce
Institution	University of Oxford
Department	Sir William Dunn Sch of Pathology
Funding type	Research
Value (£)	259,000
Status	Completed
Type	Research Grant
Start date	01/03/2002
End date	28/02/2005
Duration	36 months

Abstract

We have isolated new ligands, composed of 2'F-modified nucleic acids, that have high affinity and specificity for PrP from rodents, ungulates and humans. In contrast with alternative PrP ligands, these have a higher affinity for the beta- sheet-rich, abnormal conformations associated with infectious prions than for the normal , alpha helix-rich form found in healthy individuals. As part of a programme of research for the exploitation of these aptamers in diagnostic and other applications, largely funded by industry, we propose here to exploit their properties in order to gain fundamental insights into the molecular pathogenesis of TSEs. We will do this by using the aptamers in analytical and diagnostic formats developed under commercial sponsorship, to study samples from experimentally infected rodents, and subsequently in veterinary and clinical samples. A key advantage of our approach is that it does not rely on protease resistance for discrimination between PrP forms and can therefore be used to investigate potentially important intermediate steps in pathogenesis that have been hidden heretofore. We know for example, that it is not always possible to detect protease-resistant PrPsc in tissues that contain TSE infectivity and cytopathic changes. In addition to the benefit to the general understanding of TSE pathogenesis, the knowledge gained will both help validate the developing diagnostic tools and circumscribe the range of hazardous tissues and fluids that need to be investigated in veterinary, clinical and food safety procedures.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Biology Spongiform Encephalopathies - Diagnostics (BSD) [2000]
Funding Scheme	X – not Funded via a specific Funding Scheme

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