@article{ref1,
title="Re-Assembled Botulinum Neurotoxin Inhibits CNS Functions without Systemic Toxicity",
journal="Toxins (Basel)",
year="2011",
author="Ferrari, Enrico and Maywood, Elizabeth S. and Restani, Laura and Caleo, Matteo and Pirazzini, Marco and Rossetto, Ornella and Hastings, Michael H. and Niranjan, Dhevahi and Schiavo, Giampietro and Davletov, Bazbek",
volume="3",
number="4",
pages="345-355",
abstract="The therapeutic potential of botulinum neurotoxin type A (BoNT/A) has recently been widely recognized. BoNT/A acts to silence synaptic transmission via specific proteolytic cleavage of an essential neuronal protein, SNAP25. The advantages of BoNT/A-mediated synaptic silencing include very long duration, high potency and localized action. However, there is a fear of possible side-effects of BoNT/A due to its diffusible nature which may lead to neuromuscular blockade away from the injection site. We recently developed a &quot;protein-stapling&quot; technology which allows re-assembly of BoNT/A from two separate fragments. This technology allowed, for the first time, safe production of this popular neuronal silencing agent. Here we evaluated the re-assembled toxin in several CNS assays and assessed its systemic effects in an animal model. Our results show that the re-assembled toxin is potent in inhibiting CNS function at 1 nM concentration but surprisingly does not exhibit systemic toxicity after intraperitoneal injection even at 200 ng/kg dose. This shows that the re-assembled toxin represents a uniquely safe tool for neuroscience research and future medical applications.<p /><p>Language: en</p>",
language="en",
issn="2072-6651",
doi="10.3390/toxins3040345",
url="http://dx.doi.org/10.3390/toxins3040345"
}