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

ReferenceBBS/E/I/00000956
Principal Investigator / Supervisor Dr Moira Bruce
Co-Investigators /
Co-Supervisors
Institution The Pirbright Institute
DepartmentThe Pirbright Institute Department
Funding typeResearch
Value (£) 8,017
StatusCompleted
TypeInstitute Project
Start date 01/03/2002
End date 28/02/2005
Duration36 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 TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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