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CRISPR\u2010mediated base editing has emerged as a powerful method for modeling diseases caused by SNVs, particularly in zebrafish, which serve as an excellent platform for investigating disease mechanisms and conducting drug screenings. However, existing cytosine base editors (CBEs) for zebrafish often have broad editing windows and strong sequence preferences, limiting their effectiveness. In this study, zebrafish (z) TadA\u2010derived cytosine base editors, termed zTadA\u2010CBEs, are developed by introducing key mutations into the TadA8e enzyme. These novel editors demonstrate improved efficiency and precision in cytosine base editing. Specifically, zTadA\u2010BE4max and zTadA\u2010BEmv offer complementary editing windows, while zTadA\u2010SpRY\u2010BE4max allows for PAM\u2010flexible editing. Using zTadA\u2010CBEs, a precise disease model for Axenfeld\u2010Rieger syndrome is established, and created two new models for Hermansky\u2010Pudlak syndrome. Additionally, a novel albinism model carrying two pathogenic SNVs in the F0 generation is developed. By employing specifically designed sgRNA, the\n                    <jats:italic>\n                      fms\n                      <jats:sup>ts\u00b1<\/jats:sup>\n                    <\/jats:italic>\n                    missense mutation is corrected back to the wild\u2010type nucleotide (C &gt; T), successfully restoring macrophage levels to normal. These findings underscore the potential of zTadA\u2010CBEs to enhance genome editing techniques and their applications in developing therapies for SNV\u2010related disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.202411478","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T09:14:27Z","timestamp":1739783667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sequence Context\u2010Agnostic TadA\u2010Derived Cytosine Base Editors for Genome\u2010Wide Editing in Zebrafish"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1724-9063","authenticated-orcid":false,"given":"Shaohui","family":"Zheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Brain Cognition and Education Sciences Ministry of Education South China Normal University  Guangzhou 510631 China"},{"name":"Institute for Brain Research and Rehabilitation and 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