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Several factors contribute to tumor progression, including increased MMP9. Recently, CRISPR\u2010Cas9 and immunotherapy have offered high specificity for treatments; therefore, we edited MMP9 using CRISPR\u2010Cas9 methodology to inhibit metastatic mechanisms and evaluated potential synergy with BCG and anti\u2010PD\u2010L1 therapy. We performed CRISPR\u2010Cas9 gene editing using an RNP complex in the MB49 murine BC cell line. Gene expression of MMPs, integrins, and BAX was analyzed, along with protein expression. Cells were divided into a Scramble control group and CRISPR\u2010Cas9 for the MMP9 edited group (MMP9\u2212\/\u2212). Female C57BL\/6 mice received orthotopic BC cells (scramble and MMP9\u2212\/\u2212 groups) treated with BCG and anti\u2010PD\u2010L1. Statistical analyses were performed using\n                    <jats:italic>t<\/jats:italic>\n                    test or ANOVA. MMP9 gene and protein expression were reduced in the MMP9\u2212\/\u2212 group compared with the scramble group. No differences were observed in other MMPs. Decreased ITGB3, increased BAX gene expression, as well as reduced migration and adhesion to ECM were observed in the MMP9\u2212\/\u2212 group. Animals in the scramble group showed greater weight loss and lower survival than treated groups. Overall, MMP9 modulated key cellular mechanisms, but did not show synergistic effects with BCG and anti\u2010PD\u2010L1 in\u00a0vivo.\n                  <\/jats:p>","DOI":"10.1002\/iub.70130","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:46:16Z","timestamp":1788842776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MMP9<\/scp>\n                    Knockout by\n                    <scp>CRISPR<\/scp>\n                    \u2010Cas9 Reduces Bladder Cancer Malignancy But Does Not Synergize With\n                    <scp>BCG<\/scp>\n                    and Anti\u2010\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    in an Orthotopic Mouse Model"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5624-3798","authenticated-orcid":false,"given":"Juliana Alves 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Vilas","family":"Boas Caetano","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Investigation (LIM55), Urology Department University of Sao Paulo Medical School  Sao Paulo Brazil"},{"name":"Moriah Institute of Science and Education (MISE) Hospital Moriah  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4854-9302","authenticated-orcid":false,"given":"Karina Serafim da","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Investigation (LIM55), Urology Department University of Sao Paulo Medical School  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Mie","family":"Mioshi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Investigation (LIM55), Urology Department University of Sao Paulo Medical School  Sao Paulo 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