{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:41:55Z","timestamp":1789774915818,"version":"4.0.1"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Orphan Kidney Diseases (ORKiD) healthcare network","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Agence Nationale de la Recherche under \u201cInvestissements d\u2019avenir\u201d program","award":["ANR-10-IAHU-01"],"award-info":[{"award-number":["ANR-10-IAHU-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:p>\n                    Kidney organoids are an emerging tool for disease modeling, especially genetic diseases. Among these diseases, X-linked Alport syndrome (XLAS) is a hematuric nephropathy affecting the glomerular basement membrane (GBM) secondary to pathogenic variations in the\n                    <jats:italic>COL4A5<\/jats:italic>\n                    gene encoding the \u03b15 subunit of type IV collagen [\u03b15(IV)]. In patients carrying pathogenic variations affecting splicing, the use of antisense oligonucleotides (ASOs) offers immense therapeutic hope. In this study, we develop a framework combining the use of patient-derived cells and kidney organoids to provide evidence of the therapeutic efficacy of ASOs in XLAS patients. Using multiomics analysis, we describe the development of GBM in WT and mutated human kidney organoids. We show that GBM maturation is a dynamic process, which requires long organoid culture. Then, using semi-automated quantification of \u03b15(IV) at basement membranes in organoids carrying the splicing variants identified in patients, we demonstrate the efficacy of ASO treatment for \u03b15(IV) restoration. These data contribute to our understanding of the development of GBM in kidney organoids and pave the way for a therapeutic screening platform for patients.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.194759","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T17:02:57Z","timestamp":1766077377000},"source":"Crossref","is-referenced-by-count":4,"title":["Splice modulation of COL4A5 reinstates collagen IV assembly in an organoid model of Alport syndrome"],"prefix":"10.1172","volume":"11","author":[{"given":"Hassan","family":"Saei","sequence":"first","affiliation":[{"name":"Laboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Universit\u00e9 Paris Cite\u0301, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Estebe","sequence":"additional","affiliation":[{"name":"Laboratory of Hereditary Kidney Diseases, INSERM UMR 1163, Imagine Institute, Universit\u00e9 Paris 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