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We have designed and discovered a series of highly efficient cocaine hydrolases, including CocH5-Fc(M6) which is the currently known as the most efficient cocaine hydrolase with both the highest catalytic activity against (\u2212)-cocaine and the longest biological half-life in rats. In the present study, we characterized the time courses of protein appearance, pH, structural integrity, and catalytic activity against cocaine in vitro and in vivo of a CocH5-Fc(M6) bulk drug substance produced in a bioreactor for its in vitro and in vivo stability after long-time storage under various temperatures (\u2212\u200980, \u2212\u200920, 4, 25, or 37\u00a0\u00b0C). Specifically, all the tested properties of the CocH5-Fc(M6) protein did not significantly change after the protein was stored at any of four temperatures including \u2212\u200980, \u2212\u200920, 4, and 25\u00a0\u00b0C for\u2009~\u200918\u00a0months. In comparison, at 37\u00a0\u00b0C, the protein was less stable, with a half-life of\u2009~\u200982\u00a0days for cocaine hydrolysis activity. Additionally, the in vivo studies further confirmed the linear elimination PK profile of CocH5-Fc(M6) with an elimination half-life of\u2009~\u20099\u00a0days. All the in vitro and in vivo data on the efficacy and stability of CocH5-Fc(M6) have consistently demonstrated that CocH5-Fc(M6) has the desired in vitro and in vivo stability as a promising therapeutic candidate for treatment of cocaine use disorder.<\/jats:p>","DOI":"10.1038\/s41598-024-61646-7","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T19:02:03Z","timestamp":1715626923000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase"],"prefix":"10.1038","volume":"14","author":[{"given":"Linyue","family":"Shang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline J.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnathan E.","family":"LeSaint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet","family":"Kyomuhangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise C.","family":"Maul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Guo","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"61646_CR1","unstructured":"FDA News Release on October 04, 2023: FDA Takes Steps to Advance the Development of Novel Therapies for Stimulant Use Disorders (https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-takes-steps-advance-development-novel-therapies-stimulant-use-disorders?utm_medium=email&utm_source=govdelivery) (2023)."},{"key":"61646_CR2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2147\/SAR.S337338","volume":"13","author":"EKC Schwartz","year":"2022","unstructured":"Schwartz, E. 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