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Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies
Authors:Stöger  Eva  Vaquero  Carmen  Torres  Esperanza  Sack  Markus  Nicholson  Liz  Drossard  Jürgen  Williams   Sarah  Keen   Duncan  Perrin   Yolande  Christou   Paul  Fischer   Rainer
Affiliation:(1) John Innes Centre, Norwich Research Park, Colney Lane, Norwich, NR4 7UH, UK;(2) Institute for Biology I, RWTH Aachen, Worringerweg 1, 52074 Aachen, Germany
Abstract:This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 mgrg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.
Keywords:transgenic cereals  molecular pharming  antibodies  carcinoembryonic antigen  single-chain Fv fragment  particle bombardment
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