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Transl. Med."],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:p>\n                    Mutations in the transcription factor gene\n                    <jats:italic toggle=\"yes\">Wilms Tumor 1<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">WT1<\/jats:italic>\n                    ) are one of the leading causes of congenital glomerular disease, characterized by severe urinary protein loss and glomerular scarring. No disease-modifying therapies exist for WT1 glomerulopathies, and affected children rely on dialysis or kidney transplantation. We evaluated a previously uncharacterized treatment in a mouse model with an orthologous human mutation in\n                    <jats:italic toggle=\"yes\">Wt1<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Wt1<\/jats:italic>\n                    <jats:sup>\n                      +\n                      <jats:italic toggle=\"yes\">\/R394W<\/jats:italic>\n                    <\/jats:sup>\n                    ) that replicates the pathology of WT1 glomerulopathy. Lipid nanocomplexes were engineered to target integrin \u03b1v\u03b23 for efficient delivery of mRNA to primary podocytes and glomerular endothelial cells in vitro. A minimally invasive ultrasound-guided renal artery injection enabled precise and specific kidney localization in vivo, a finding not replicated by systemic administration. Nanocomplex-derived protein localized in glomeruli for up to 7 days in healthy and diseased mice. This platform was then used to perform an interventional preclinical trial in\n                    <jats:italic toggle=\"yes\">\n                      Wt1\n                      <jats:sup>+\/R394W<\/jats:sup>\n                    <\/jats:italic>\n                    mice, delivering\n                    <jats:italic toggle=\"yes\">angiopoietin-1<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Angpt1<\/jats:italic>\n                    ) mRNA, a vascular growth factor critical for glomerular health that is reduced in\n                    <jats:italic toggle=\"yes\">\n                      Wt1\n                      <jats:sup>+\/R394W<\/jats:sup>\n                    <\/jats:italic>\n                    podocytes.\n                    <jats:italic toggle=\"yes\">Angpt1<\/jats:italic>\n                    nanocomplex therapy reduced albuminuria, preserved glomerular endothelial integrity, prevented podocyte loss, and alleviated glomerulosclerosis in\n                    <jats:italic toggle=\"yes\">\n                      Wt1\n                      <jats:sup>+\/R394W<\/jats:sup>\n                    <\/jats:italic>\n                    mice. These findings demonstrate the therapeutic potential of this targeted approach for WT1 glomerulopathy and provide a foundation for clinical translation to improve outcomes in children with glomerular disease.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adv1289","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:58:18Z","timestamp":1786557498000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound-guided renal artery administration of angiopoietin-1 RNA therapy slows the progression of preclinical WT1 glomerular disease"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8042-3665","authenticated-orcid":true,"given":"Saif N.","family":"Malik","sequence":"first","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."},{"name":"UCL Centre for Kidney and Bladder Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9785-4528","authenticated-orcid":true,"given":"Jennifer C.","family":"Chandler","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."},{"name":"UCL Centre for Kidney and Bladder Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1473-9757","authenticated-orcid":true,"given":"Ruhina","family":"Maeshima","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kolatsi-Joannou","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."},{"name":"UCL Centre for Kidney and Bladder Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6014-3562","authenticated-orcid":true,"given":"William J.","family":"Mason","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."},{"name":"UCL Centre for Kidney and Bladder Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren G.","family":"Russell","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."},{"name":"UCL Centre for Kidney and Bladder Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-6116","authenticated-orcid":true,"given":"Shunping","family":"Han","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanis","family":"Harfouche","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."},{"name":"UCL Centre for Kidney and Bladder Health, London WC1N 1EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-0394","authenticated-orcid":true,"given":"Daniyal J.","family":"Jafree","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London WC1N 1EH, UK."},{"name":"UCL Centre for Kidney and Bladder Health, London WC1N 1EH, UK."},{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1RQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6344-9325","authenticated-orcid":true,"given":"Emily A. 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