{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:02:38Z","timestamp":1779696158928,"version":"3.53.1"},"reference-count":35,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"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":["Human Gene Therapy"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>\n                    In order to support the clinical application of hematopoietic stem cell (HSC) gene therapy for mucopolysaccharidosis I (MPS I), biosafety studies were conducted to assess the toxicity and tumorigenic potential, as well as the biodistribution of HSCs and progenitor cells (HSPCs) transduced with lentiviral vectors (LV) encoding the cDNA of the alpha-iduronidase (\n                    <jats:italic toggle=\"yes\">IDUA<\/jats:italic>\n                    ) gene, which is mutated in MPS I patients. To this goal, toxicology and biodistribution studies were conducted, employing Good Laboratory Practice principles. Vector integration site (IS) studies were applied in order to predict adverse consequences of vector gene transfer and to obtain HSC-related information. Overall, the results obtained in these studies provided robust evidence to support the safety and tolerability of high-efficiency LV-mediated gene transfer and above-normal IDUA enzyme expression in both murine and human HSPCs and their\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    progeny. Taken together, these investigations provide essential safety data to support clinical testing of HSC gene therapy in MPS I patients. These studies also underline criticisms associated with the use of currently available models, and highlight the value of surrogate markers of tumorigenicity that may be further explored in the future. Notably, biological evidence supporting the efficacy of gene therapy on MPS I disease and its feasibility on patients' HSCs were also generated, employing clinical-grade LVs. Finally, the clonal contribution of LV-transduced HSPCs to hematopoiesis along serial transplantation was quantified in a minimum of 200\u2013300 clones, with the different level of repopulating cells in primary recipients being reflected in the secondary.\n                  <\/jats:p>","DOI":"10.1089\/hum.2016.068","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T22:55:41Z","timestamp":1468882541000},"page":"813-829","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":42,"title":["Preclinical Testing of the Safety and Tolerability of Lentiviral Vector\u2013Mediated Above-Normal Alpha-L-Iduronidase Expression in Murine and Human Hematopoietic Cells Using Toxicology and Biodistribution Good Laboratory Practice Studies"],"prefix":"10.1177","volume":"27","author":[{"given":"Ilaria","family":"Visigalli","sequence":"first","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Delai","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ferro","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cecere","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Vezzoli","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sanvito","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]},{"name":"IRCCS San Raffaele Scientific Institute","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Chanut","sequence":"additional","affiliation":[{"name":"Glaxo Smith Kline R&D UK Safety Assessment","place":["United Kingdom"]},{"name":"Sanofi","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Benedicenti","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Spinozzi","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Wynn","sequence":"additional","affiliation":[{"name":"Royal Manchester Children's Hospital","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Calabria","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Naldini","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]},{"name":"Vita Salute San Raffaele University","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Montini","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Cristofori","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]},{"name":"Glaxo Smith Kline R&D UK Safety Assessment","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Biffi","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,10,1]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"Neufeld EF Muenzer J. 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