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Novel approaches to target infectious diseases: the utility of Auger electrons and scFvs for imaging and control

Rathje, Claudia Cattoni (2014) Novel approaches to target infectious diseases: the utility of Auger electrons and scFvs for imaging and control. Doctor of Philosophy (PhD) thesis, University of Kent,.

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Abstract

With an increasing number of infectious agents resistant to one or more existing antibiotics, there is a global requirement for new therapeutics. One possible method for treatment of infectious diseases proposed in this study is the adaptation of a technique developed for cancer treatment, targeted radionuclide therapy, with particular interest in Auger electron radiation. Auger electrons are short range and low energy particles emitted from a range of radioactive isotopes. As a targeting agent, the antimicrobial peptide fragment UBI 29-41 was used. Antimicrobial peptides have a broad range of target microorganisms, ideal for toxicological studies of Auger electrons. Here, the baseline toxicity of UBI 29-41 was established in a range of model organisms. This enabled the analysis of the toxic effect of Auger electron emitting radio-nuclides using the isotope125I. Although no direct toxic effect was observed with this particular isotope, the labelling allows easy replacement with more potent isotopes. To further develop the targeting agent a lipoarabinomannan (LAM) specific single-chain variable fragment (scFv) was developed. LAM is a glycolipid and virulence factor associated with M. tuberculosis, the primary cause of tuberculosis in humans. By isolating the variable domains of a LAM specific monoclonal antibody, linked via a poly-glycine linker, the scFv was assembled in silico. The nucleotide sequence was optimised for and transfected into a Pichia pink expression system. Expression was successful with a ~27kDa product being secreted. The novel anti-LAM scFv generated in this study combined with the potential toxic effects of Auger electrons could provide a new avenue for the treatment and diagnosis of tuberculosis.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Lloyd, Dan
Uncontrolled keywords: Auger electrons, antibiotic, scFv, antimicrobial peptides, radiation, tuberculosis, protein expression, scFv design, Pichia pink, bacteria, yeast
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Users 1 not found.
Date Deposited: 27 Feb 2015 12:12 UTC
Last Modified: 29 May 2019 14:16 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/47432 (The current URI for this page, for reference purposes)
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