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New Modified Recombinant Botulinum Neurotoxin Type F with Enhanced Potency

1
Ipsen Bioinnovation, 102 Park Drive, Abingdon OX14 3YS, UK
2
Ipsen Innovation, 5 Avenue du Canada, 91940 Les Ulis, France
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Authors to whom correspondence should be addressed.
Toxins 2021, 13(12), 834; https://doi.org/10.3390/toxins13120834
Received: 26 October 2021 / Revised: 9 November 2021 / Accepted: 16 November 2021 / Published: 24 November 2021
(This article belongs to the Special Issue Structure and Function of Clostridial and Botulinum-Like Neurotoxins)
Botulinum neurotoxins (BoNTs) are notorious toxins and powerful agents and can be lethal, causing botulism, but they are also widely used as therapeutics, particularly to treat neuromuscular disorders. As of today, the commercial BoNT treatments available are from native A or B serotypes. Serotype F has shown efficacy in a clinical trial but has scarcely been used, most likely due to its medium duration of effect. Previously, the uniqueness of the light chain of the F7 subtype was identified and reported, showing an extended interaction with its substrates, VAMPs 1, 2 and 3, and a superior catalytic activity compared to other BoNT/F subtypes. In order to more extensively study the properties of this neurotoxin, we engineered a modified F7 chimera, mrBoNT/F7-1, in which all the regions of the neurotoxin were identical to BoNT/F7 except the activation loop, which was the activation loop from BoNT/F1. Use of the activation loop from BoNT/F1 allowed easier post-translational proteolytic activation of the recombinant protein without otherwise affecting its properties. mrBoNT/F7-1 was expressed, purified and then tested in a suite of in vitro and in vivo assays. mrBoNT/F7-1 was active and showed enhanced potency in comparison to both native and recombinant BoNT/F1. Additionally, the safety profile remained comparable to BoNT/F1 despite the increased potency. This new modified recombinant toxin F7 could be further exploited to develop unique therapeutics to address unmet medical needs. View Full-Text
Keywords: botulinum neurotoxin; recombinant protein; potency; safety profile; in vivo botulinum neurotoxin; recombinant protein; potency; safety profile; in vivo
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MDPI and ACS Style

Burgin, D.; Périer, C.; Hackett, G.; Elliott, M.; Kwan, D.; Hornby, F.; Mir, I.; Maignel, J.; Liu, S.M.; Beard, M. New Modified Recombinant Botulinum Neurotoxin Type F with Enhanced Potency. Toxins 2021, 13, 834. https://doi.org/10.3390/toxins13120834

AMA Style

Burgin D, Périer C, Hackett G, Elliott M, Kwan D, Hornby F, Mir I, Maignel J, Liu SM, Beard M. New Modified Recombinant Botulinum Neurotoxin Type F with Enhanced Potency. Toxins. 2021; 13(12):834. https://doi.org/10.3390/toxins13120834

Chicago/Turabian Style

Burgin, David, Cindy Périer, Gavin Hackett, Mark Elliott, Daniel Kwan, Fraser Hornby, Imran Mir, Jacquie Maignel, Sai M. Liu, and Matthew Beard. 2021. "New Modified Recombinant Botulinum Neurotoxin Type F with Enhanced Potency" Toxins 13, no. 12: 834. https://doi.org/10.3390/toxins13120834

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