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Immunomodulation of enzyme function in plants by single-domain antibody fragments

Abstract

Immunomodulation involves the use of antibodies to alter the function of molecules and is an emerging tool for manipulating both plant and animal systems. To realize the full potential of this technology, two major obstacles must be overcome. First, most antibodies do not function well intracellularly because critical disulfide bonds cannot form in the reducing environment of the cytoplasm or because of difficulties in targeting to subcellular organelles. Second, few antibodies bind to the active sites of enzymes and thus they generally do not neutralize enzyme function. Here we show that the unique properties of single-domain antibodies from camelids (camels and llamas) can circumvent both these obstacles. We demonstrate that these antibodies can be correctly targeted to subcellular organelles and inhibit enzyme function in plants more efficiently than antisense approaches. The use of these single-domain antibody fragments may greatly facilitate the successful immunomodulation of metabolic pathways in many organisms.

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Figure 1: Schematic diagram of the llama IgG structure.
Figure 2: Neutralization of SBE A activity by llama VHH antibodies.
Figure 3: VHH antibody fragments are correctly processed in planta.
Figure 4: Amylose content of purified starches.
Figure 5: SBE characterization in potato tubers.

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Acknowledgements

The authors wish to thank Paul van der Logt and colleagues for preparation of the llama “one pot” antibody library, and Tina Sanders, Alice Belton and Bob Cowper for the generation and maintenance of the potato plants. Special thanks go to Tony Lee and Theo Verrips for their unwavering support for this project.

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Correspondence to Stephen A. Jobling.

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Jobling, S., Jarman, C., Teh, MM. et al. Immunomodulation of enzyme function in plants by single-domain antibody fragments. Nat Biotechnol 21, 77–80 (2003). https://doi.org/10.1038/nbt772

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