Rexis plans to develop a broad acting antitoxin to Clostridium botulinum Neurotoxin Serotypes A, B and E (possibly C, D, F and G) offering high stability, bio-distribution and extended protection due to long circulating half-life. The anti-toxin will be manufactured cost effectively using a yeast fermentation process to meet demand in cases of mass exposure from acts of Bioterrorism. The specific aims are to develop and produce a lead candidate anti-toxin Trans-body TM and to evaluate its neutralizing potency in a standardized animal model at Battelle Laboratories. To make a Trans-body, toxin-binding peptide sequences, derived from phage display, will be engineered within the scaffold of modified transferrin. The peptide retains its binding activity but assumes the long half-life of the transferrin carrier. Botulism results from the binding of the neurotoxin to the receptor, which then mediates its translocation into the cell. Internalized neurotoxin blocks neurotransmitter release, and leads to muscle paralysis and possibly death. The antitoxin Trans-body is intended to neutralize the neurotoxin by preventing it from binding its target receptor. The properties of long half-life and high bio-distribution allow for a fast acting antitoxin with extended neutralizing protection. This technology offers an alternative approach to antibodies as direct blocking ligands, with the advantage of broader activity and easier manufacturing.
Thesaurus Terms: Clostridium botulinum, antitoxin, biotherapeutic agent, botulinum toxin, chimeric protein, drug design /synthesis /production, genetic manipulation, immunologic substance development /preparation, neurotoxin disease /disorder model, drug screening /evaluation, fermentation, neutralizing antibody, pharmacokinetics, transferrin antibody neutralization test, biotechnology, bioterrorism /chemical warfare, laboratory mouse, laboratory rabbit
