{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:52:59Z","timestamp":1788864779582,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP22K18198"],"award-info":[{"award-number":["JP22K18198"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, cleaves proteins involved in neurotransmitter release, thereby triggering flaccid paralyses, which are responsible for botulism. BoNT is classified into seven serotypes (BoNT\/A-G); BoNT\/A and BoNT\/B are used as medical therapeutics and anti-wrinkle reagents. In this study, we investigated the efficacy of BoNT\/CD, a mosaic toxin of BoNT\/C and BoNT\/D, to assess its potential as a therapeutic alternative for BoNT\/A. In a cultured neuron assay, BoNT\/CD cleaved syntaxin and SNAP-25 with higher efficacy than BoNT\/C and BoNT\/A. Intramuscularly administrated BoNT\/CD induced dose-dependent muscle paralysis, and the paralysis lasted ~21 days in a mouse digit abduction score assay (BoNT\/A-induced paralysis lasted ~30 days). BoNT\/C failed to induce local paralysis without systemic toxicity. Multiple alignment analyses of the amino acid sequences of the receptor binding domain (HC) of eight BoNT\/CDs and two BoNT\/Ds showed sequence clustering in five groups. Comparing BoNT\/CD strain 003-9 (BoNT\/CD003-9) and strain 6813 (BoNT\/CD6813) showed that both BoNT\/CDs displayed similar efficacies in cultured neurons, but BoNT\/CD003-9 displayed higher efficacy in a mouse model than BoNT\/CD6813. These findings suggest that BoNT\/CD may be a potential alternative for patients who do not respond to existing BoNT-based therapeutics.<\/jats:p>","DOI":"10.3390\/toxins15020123","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T04:21:43Z","timestamp":1675398103000},"page":"123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of Serotype CD Mosaic Botulinum Neurotoxin in Comparison with Serotype C and A"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4815-9323","authenticated-orcid":false,"given":"Shin-Ichiro","family":"Miyashita","sequence":"first","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shura","family":"Karatsu","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Fujiishi","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4356-1089","authenticated-orcid":false,"given":"I Hsun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamaki","family":"Morobishi","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Hosoya","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Urology, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Surgery, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimasa","family":"Sagane","sequence":"additional","affiliation":[{"name":"Department of Food, Aroma and Cosmetic Chemistry, Faculty of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rasetti-Escargueil, C., Lemichez, E., and Popoff, M.R. 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