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filingDate 2008-12-10-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_d0c840af04d37599c9b66770e863f4c6
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publicationDate 2009-06-18-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber WO-2009076426-A1
titleOfInvention Engineering zymogen for conditional toxicity
abstract The ADP-ribosyltransferase, Vip2, exerts its intracellular toxicity in insects by modifying actin and preventing actin polymerization. Due to the nature of this toxin, expression of Vip2 in planta is lethal to the plant. Described herein are methods of making zymogens of toxic proteins that are benign in a non-target organism and are activated in a target organism. Disclosed herein are methods of engineering a random propeptide library at a terminus of a toxic protein and selecting for malfunctional variants in yeast. Using this method a selected proenzyme possesses reduced enzymatic activity as compared to the wild-type Vip2 protein, but remains a potent toxin towards corn rootworm larvae. The Vip2 zymogen can be proteolytically activated by corn rootworm digestive proteases.
priorityDate 2007-12-11-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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