MOLECULAR VARIABLES IN FUSION TOXIN EFFICACY

Medical University Of South Carolina, Charleston SC

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Abstract

The feasibility of expression of a ricin toxin transgene in plant tobacco cells was demonstrated. This system offers advantages over other expression systems that have been used: 1) ability to perform complex post- translational modifications, 2) strong signal peptide sequences to protect the ribosomes from ricin toxicity, 3) greater ease of mass production. Using this expression system the molecular variables important in the construction of a ricin fusion toxin with targeted cell killing and minimal non-specific toxicity will be investigated. The FIRST AIM is to define the role of the cleavable interchain disulfide bond for ricin toxicity; the SECOND AIM is to define the ability of the plant expression system to produce double and triple ricin B chain mutants; the THIRD AIM is to use cytoxic qualities of a KDEL-modified ricin toxin; the FOURTH AIM is to use the knowledge from the first 3 AIMS to design a single-chain antibody (against neuroblastoma antigen GD2) ricin fusion protein.