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Here, we engineer CTBPro, a next\u2010generation CTB\u2010based tracer, by genetically fusing CTB to the ultra\u2010stable fluorescent protein mBaoJin. In vitro, CTBPro exhibits an estimated nine\u2010fold enhancement in peak fluorescence output per mole of tracer compared to conventional CTB\u2010Alexa488 conjugates. This enhanced brightness translates to superior in vivo tracing across four distinct administration routes\u2014intraparenchymal, peripheral (renal), cerebrospinal fluid (CSF), and intravenous\u2014enabling high\u2010fidelity labeling of fine somatic and axonal details. Critically, because CTBPro is an entirely protein\u2010based fusion, it can be genetically encoded. We leverage this property by packaging CTBPro into an AAV\u2010BI30 serotype vector, which enables endothelial\u2010specific expression that recapitulates the distinctive labeling pattern of intravenous injection. Taken together, CTBPro overcomes the fundamental limitations of CTB\u2010based tracers. Its superior brightness, versatile administration, and multimodal stability establish it as a powerful and extensible tool for high\u2010resolution neuronal circuit tracing.<\/jats:p>","DOI":"10.1002\/advs.202522249","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:53:19Z","timestamp":1776855199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CTBPro: A Next\u2010Generation Cholera Toxin Subunit B\u2010Based Neuroanatomical Tracer With Superior Brightness, Stability, and Sensitivity for Enhanced Neural Circuit Mapping"],"prefix":"10.1002","volume":"13","author":[{"given":"Xinghua","family":"Quan","sequence":"first","affiliation":[{"name":"Laboratory of Neurovascular Biology, School of Life Sciences Westlake University  Hangzhou Zhejiang China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine  Hangzhou Zhejiang 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