[HTML][HTML] Engineering of botulinum neurotoxins for biomedical applications

RP Webb - Toxins, 2018 - mdpi.com
RP Webb
Toxins, 2018mdpi.com
Botulinum neurotoxins (BoNTs) have been used as therapeutic agents in the clinical
treatment of a wide array of neuromuscular and autonomic neuronal transmission disorders.
These toxins contain three functional domains that mediate highly specific neuronal cell
binding, internalization and cytosolic delivery of proteolytic enzymes that cleave proteins
integral to the exocytosis of neurotransmitters. The exceptional cellular specificity, potency
and persistence within the neuron that make BoNTs such effective toxins, also make them …
Botulinum neurotoxins (BoNTs) have been used as therapeutic agents in the clinical treatment of a wide array of neuromuscular and autonomic neuronal transmission disorders. These toxins contain three functional domains that mediate highly specific neuronal cell binding, internalization and cytosolic delivery of proteolytic enzymes that cleave proteins integral to the exocytosis of neurotransmitters. The exceptional cellular specificity, potency and persistence within the neuron that make BoNTs such effective toxins, also make them attractive models for derivatives that have modified properties that could potentially expand their therapeutic repertoire. Advances in molecular biology techniques and rapid DNA synthesis have allowed a wide variety of novel BoNTs with alternative functions to be assessed as potential new classes of therapeutic drugs. This review examines how the BoNTs have been engineered in an effort to produce new classes of therapeutic molecules to address a wide array of disorders.
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