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Novel Native and Engineered Botulinum Neurotoxins

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Botulinum Toxin Therapy

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 263))

Abstract

Botulinum neurotoxins (BoNTs), produced by Clostridia and other bacteria, are the most potent toxins known. Their cleavage of the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) proteins in neurons prevents the release of neurotransmitters, thus resulting in the muscle paralysis that is characteristic of botulism. This mechanism of action has been exploited for a variety of therapeutic and cosmetic applications of BoNTs. This chapter provides an overview of the native BoNTs, including the classical serotypes and their clinical use, mosaic BoNTs, and novel BoNTs that have been recently identified in clostridial and non-clostridial strains. In addition, the modular structure of native BoNTs, which are composed of a light chain and a heavy chain, is amenable to a multitude of novel fusions and mutations using molecular biology techniques. These novel recombinant BoNTs have been used or are being developed to further characterize the biology of toxins, to assist in vaccine production, to serve as delivery vehicles to neurons, and to be utilized as novel therapeutics for both neuronal and non-neuronal cells.

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Acknowledgments

The authors thank Dina Anderson, Birgitte Jacky, Mariana Nelson, and Edwin Vazquez-Cintron (Allergan plc) for reviewing the chapter and Maria Rivero (Allergan plc) for the graphics. Medical writing and editorial assistance was provided by Jennifer L. Giel, PhD, on behalf of Evidence Scientific Solutions, Inc, Philadelphia, PA, and was funded by Allergan plc, Dublin, Ireland.

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Authors and Affiliations

  1. Allergan plc, Irvine, CA, USA

    Lance Steward, Mitchell F. Brin & Amy Brideau-Andersen

  2. University of California, Irvine, CA, USA

    Mitchell F. Brin

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  1. Lance Steward
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  2. Mitchell F. Brin
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Correspondence to Amy Brideau-Andersen .

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  1. Akrivista and Whitecap Biosciences, Irvine, CA, USA

    Scott M. Whitcup

  2. Bethesda, MD, USA

    Mark Hallett

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Steward, L., Brin, M.F., Brideau-Andersen, A. (2020). Novel Native and Engineered Botulinum Neurotoxins. In: Whitcup, S.M., Hallett, M. (eds) Botulinum Toxin Therapy. Handbook of Experimental Pharmacology, vol 263. Springer, Cham. https://doi.org/10.1007/164_2020_351

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