{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:13:12Z","timestamp":1789409592051,"version":"build-2803163510"},"reference-count":84,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":47,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Riaan Research Initiative","award":["RRI-1212"],"award-info":[{"award-number":["RRI-1212"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>\n                    Cockayne syndrome (CS) is an autosomal recessive, progressive developmental and neurodegenerative disease. Approximately 30% of cases are caused by mutations in the\n                    <jats:italic>ERCC8\/CSA<\/jats:italic>\n                    gene. Patients with CS present with cutaneous photosensitivity, growth failure, shorter life span, and a progressive degeneration of the central nervous system. Loss-of-function mutations in CSA result in deficiencies in transcription-coupled nucleotide excision repair. Currently, no therapies are available for these patients. Adeno-associated virus\u2013mediated (AAV-mediated) gene therapy offers an opportunity to address this unmet need. We designed an AAV vector encoding human CSA under a ubiquitous promoter. We tested the therapeutic efficacy of this AAV9-CSA vector by neonatal intracerebroventricular injection in the\n                    <jats:italic>\n                      Csa\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      Xpa\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mouse model. Treatment with AAV9-CSA resulted in a significant increase in life span, and broad distribution of human CSA in the brain and heart, without evidence of vector-related toxicity. Despite clear therapeutic benefit, we also observed neuroradiological abnormalities, and neuropathologic alterations, including hypomyelination, astrocytosis, and microgliosis, as well as likely life-limiting transcriptomic alterations in liver at endpoint. Nonetheless, the success of these experiments paves the way for clinical translation of an AAV gene therapy for patients with CS into humans.\n                  <\/jats:p>","DOI":"10.1172\/jci196689","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:21Z","timestamp":1785427221000},"source":"Crossref","is-referenced-by-count":0,"title":["AAV-mediated gene therapy demonstrates phenotypic rescue in a mouse model of Cockayne syndrome"],"prefix":"10.1172","volume":"136","author":[{"given":"Ana Rita","family":"Batista","sequence":"first","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aine C.","family":"Scholand","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Callahan","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKenna K.","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra M.","family":"Sion","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Mola","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennedy","family":"O\u2019Hara","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Wentworth","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine,"},{"name":"Department of Neurology,"},{"name":"MD\/PhD program, Morningside Graduate School of Biomedical Sciences, T.H. 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