{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:37:40Z","timestamp":1777905460063,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The CRISPR Journal"],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:p>\n                    Overweight females are prone to obesity-associated stress urinary incontinence (OA-SUI), and there are no definitive medical therapies for this common urologic condition. This study was designed to test the hypothesis that regenerative therapy to restore urethral striated muscle (stM) and pelvic floor muscles might represent a valuable therapeutic approach. For the\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    experiment, single-guide RNAs targeting myostatin (\n                    <jats:italic toggle=\"yes\">MSTN<\/jats:italic>\n                    ) were used for CRISPRi\/dCas9-Kruppel associated box (KRAB)-mediated gene silencing. For the\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    experiment, a total of 14 female lean ZUC-Lepr\n                    <jats:sup>fa<\/jats:sup>\n                    186 and 14 fatty ZUC-Lepr\n                    <jats:sup>fa<\/jats:sup>\n                    185 rats were used as control and CRISPRi-MSTN treated groups, respectively. The results indicated that lentivirus-mediated expression of MSTN CRISPRi\/dCas9-KRAB caused sustained downregulation of MSTN in rat L6 myoblast cells and significantly enhanced myogenesis\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    .\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    , the urethral sphincter injection of lentiviral-MSTN sgRNA and lentiviral-dCas9-KRAB significantly increased the leak point pressure, the thickness of the stM layer, the ratio of stM to smooth muscle, and the number of neuromuscular junctions. Downregulation of\n                    <jats:italic toggle=\"yes\">MSTN<\/jats:italic>\n                    with CRISPRi\/dCas9-KRAB-mediated gene silencing significantly enhanced myogenesis\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo.<\/jats:italic>\n                    It also improved urethral continence in the OA-SUI rat model.\n                  <\/jats:p>","DOI":"10.1089\/crispr.2020.0077","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T10:03:12Z","timestamp":1608544992000},"page":"562-572","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Regenerating Urethral Striated Muscle by CRISPRi\/dCas9-KRAB-Mediated Myostatin Silencing for Obesity-Associated Stress Urinary Incontinence"],"prefix":"10.1177","volume":"3","author":[{"given":"Huixing","family":"Yuan","sequence":"first","affiliation":[{"name":"Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California, USA; 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