{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:54:59Z","timestamp":1792018499506,"version":"4.4.0"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6148","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2013,8,23]]},"abstract":"<jats:title>Next-Generation Gene Therapy<\/jats:title>\n                  <jats:p>\n                    Few disciplines in contemporary clinical research have experienced the high expectations directed at the gene therapy field. However, gene therapy has been challenging to translate to the clinic, often because the therapeutic gene is expressed at insufficient levels in the patient or because the gene delivery vector integrates near protooncogenes, which can cause leukemia (see the Perspective by\n                    <jats:bold>\n                      <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6148\" page=\"853\" related-article-type=\"in-this-issue\" vol=\"341\" xlink:href=\"10.1126\/science.1242551\">Verma<\/jats:related-article>\n                    <\/jats:bold>\n                    ).\n                    <jats:bold>\n                      Biffi\n                      <jats:italic>et al.<\/jats:italic>\n                    <\/jats:bold>\n                    (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.sciencemag.org\/content\/341\/6148\/1233158.full\">1233158<\/jats:ext-link>\n                    , published online 11 July) and\n                    <jats:bold>\n                      Aiuti\n                      <jats:italic>et al.<\/jats:italic>\n                    <\/jats:bold>\n                    (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.sciencemag.org\/content\/341\/6148\/1233151.full\">1233151<\/jats:ext-link>\n                    ; published online 11 July) report progress on both fronts in gene therapy trials of three patients with metachromatic leukodystrophy (MLD), a neurodegenerative disorder, and three patients with Wiskott-Aldrich syndrome (WAS), an immunodeficiency disorder. Optimized lentiviral vectors were used to introduce functional\n                    <jats:italic>MLD<\/jats:italic>\n                    or\n                    <jats:italic>WAS<\/jats:italic>\n                    genes into the patients' hematopoietic stem cells (HSCs) ex vivo, and the transduced cells were then infused back into the patients, who were then monitored for up to 2 years. In both trials, the patients showed stable engraftment of the transduced HSC and high expression levels of functional\n                    <jats:italic>MLD<\/jats:italic>\n                    or\n                    <jats:italic>WAS<\/jats:italic>\n                    genes. Encouragingly, there was no evidence of lentiviral vector integration near proto-oncogenes, and the gene therapy treatment halted disease progression in most patients. A longer follow-up period will be needed to further validate efficacy and safety.\n                  <\/jats:p>","DOI":"10.1126\/science.1233158","type":"journal-article","created":{"date-parts":[[2013,7,12]],"date-time":"2013-07-12T00:54:00Z","timestamp":1373590440000},"source":"Crossref","is-referenced-by-count":1095,"title":["Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy"],"prefix":"10.1126","volume":"341","author":[{"given":"Alessandra","family":"Biffi","sequence":"first","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Scientific Institute, 20132 Milan, Italy."},{"name":"TIGET Pediatric Clinical Research Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy."},{"name":"Pediatric Immunohematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, 20132 Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Montini","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Scientific Institute, 20132 Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lorioli","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (TIGET), San Raffaele Scientific Institute, 20132 Milan, Italy."},{"name":"TIGET Pediatric Clinical Research Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy."},{"name":"Pediatric Immunohematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, 20132 Milan, Italy."},{"name":"Vita-Salute San Raffaele University, 20132 Milan, 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