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Abstract
Grant Number: 1R43GM080837-01 Project Title: Optimization of Codon-Pair Usage to Maximize Protein Expression in Plants
PI Information: Name Title WYCOFF, KEITH L. kwycoff@planetbiotechnology.com RESEARCH DIRECTOR Abstract: DESCRIPTION (provided by applicant): Inexpensive therapeutic recombinant proteins, such as monoclonal antibodies, can be produced using plants as "biofactories." For reasons that are unclear, the yield of antibodies has been low in practical agricultural crops, such as tobacco. We hypothesize that such generally low expression can be improved by matching the codon pair preferences of the host with the codon pairs of the recombinant genes. Work in bacterial, yeast and mammalian protein translation systems demonstrated that translational step- times are controlled by tRNA-tRNA interactions in the ribosome and that these interactions are controlled by adjacent codons (codon pairs). Thus, a designed gene can control translational step-times and improve protein expression. This technology has not yet been applied in plants. We will assemble a database of protein coding regions from tobacco, and using an algorithm developed at UC Irvine, design an IgG heavy chain gene with optimal codon-pair usage for tobacco expression (a "hot-rod" gene). We will then compare expression in tobacco of the same IgG heavy chain encoded by the "hot- rod" gene, a gene codon-optimized for tobacco, and the native human gene. If successful, the result will be a general platform technology for the quick, easy, scalable production of therapeutic human antibodies in large quantities. Planet is developing tobacco-produced recombinant proteins against several diseases including: intoxication by Botulinum Neurotoxin A (BoNT/A), the most potent toxin known and a bio-terror agent, the common cold, dental caries and intoxication by Anthrax toxin, also a bio-terror agent. All of these product-candidates could benefit from a technology that would increase expression in plants, which would result in decreases in production and purification costs, making therapeutic antibodies more affordable and widely available.
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Institution: PLANET BIOTECHNOLOGY, INC. 25571 CLAWITER RD HAYWARD, CA 94545 Fiscal Year: 2007 Department: Project Start: 20-JUL-2007 Project End: 19-JUL-2008 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: ZRG1