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

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.

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.