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However, its application in\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    has been constrained by inconsistent efficiency and limited repression amplitude. Here, we present embedded CRISPR interference (emCRISPRi), an advanced gene\u2010silencing platform that integrates transcriptional repression domains (Mxi and TRD) into a structurally flexible region of dCas9. This design significantly enhances silencing efficiency, enabling robust repression of coding genes and cis\u2010regulatory elements, particularly at transcription start site (TSS)\u2010proximal regions. emCRISPRi demonstrates improved gene\u2010silencing activity compared to RNA interference (RNAi) at several tested loci and facilitates strong phenotypic rescue via unmodified cDNA. Its versatility is demonstrated through the dissection of Hippo pathway interactions and the mitigation of TDP\u201043\u2010induced neurotoxicity in an amyotrophic lateral sclerosis (ALS) model. These findings position emCRISPRi as a transformative tool for functional genomics, enhancer studies, and disease modeling in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , with significant potential for cross\u2010species adaptation and therapeutic innovation.\n                  <\/jats:p>","DOI":"10.1002\/advs.202515849","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T18:44:08Z","timestamp":1774032248000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Embedded CRISPRi Enhances Gene\u2010Silencing Efficiency in\n                    <i>Drosophila<\/i>"],"prefix":"10.1002","volume":"13","author":[{"given":"Pengchong","family":"Fu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Suzhou Medical College Soochow University  Suzhou Jiangsu Province China"},{"name":"Gene Editing Center School of Life Science and 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