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Development of botulism antidotes will require neuronal delivery of agents that inhibit or destroy the BoNT protease. Here, we investigated the potential of engineering<jats:italic>Clostridium difficile<\/jats:italic>toxin B (TcdB) as a neuronal delivery vehicle by testing two recombinant TcdB chimeras. For AGT-TcdB chimera, an alkyltransferase (AGT) was appended to the N-terminal glucosyltransferase (GT) of TcdB. Recombinant AGT-TcdB had alkyltransferase activity, and the chimera was nearly as toxic to Vero cells as wild-type TcdB, suggesting efficient cytosolic delivery of the AGT\/GT fusion. For AGT-TcdB-BoNT\/A-Hc, the receptor-binding domain (RBD) of TcdB was replaced by the equivalent RBD from BoNT\/A (BoNT\/A-Hc). AGT-TcdB-BoNT\/A-Hc was &gt;25-fold more toxic to neuronal cells and &gt;25-fold less toxic to Vero cells than AGT-TcdB. Thus, TcdB can be engineered for cytosolic delivery of biomolecules and improved targeting of neuronal cells.<\/jats:p>","DOI":"10.1155\/2012\/760142","type":"journal-article","created":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T19:29:55Z","timestamp":1316546995000},"page":"1-9","source":"Crossref","is-referenced-by-count":3,"title":["Retargeting<i>Clostridium difficile<\/i>Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism"],"prefix":"10.1155","volume":"2012","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-7894","authenticated-orcid":true,"given":"Greice","family":"Krautz-Peterson","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, 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