{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T06:22:13Z","timestamp":1695622933288},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2000,5,1]],"date-time":"2000-05-01T00:00:00Z","timestamp":957139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2000,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lysosomal storage diseases (LSD) are considered to be appropriate disorders for gene therapy\/cell therapy. We are attempting to treat one of these disorders using a mouse model, the Sly mouse. This is an authentic model for human \u03b2\u2010glucuronidase deficiency, MPS VII. We have carried out two types of experimental protocols; <jats:italic>in vivo<\/jats:italic> gene therapy and <jats:italic>ex vivo<\/jats:italic> gene therapy using Sly mice. For <jats:italic>in vivo<\/jats:italic> gene therapy, we produced a recombinant adenovirus that expresses human \u03b2\u2010glucuronidase and administered this to Sly mice intravenously. The \u03b2\u2010glucuronidase activities in liver and spleen were elevated to 40% and 20%, respectively, of the heterozygote enzyme level at day 16. Expression persisted for at least 35 days. Pathological abnormalities improved in these tissues and urinary glycosaminoglycan excretion was reduced in treated animals. <jats:italic>ex vivo<\/jats:italic> gene therapy\/cell therapy was carried out using macrophages obtained by cultivation of bone marrow cells. Non\u2010myeloablated macrophages from normal mice were transplanted into Sly mice, and after 7 days donor cells had populated the liver and spleen. The human \u03b2\u2010glucuronidase (HBG) activity was increased in liver and spleen, although these enzyme activities subsequently fell by 38 days. The pathological improvement in Sly mice was evident at day 38 post transplantation. Furthermore, the macrophages from Sly mice were treated with retrovirus\/adenovirus vector expressing HBG activity and the glycosaminoglycan accumulation was markedly decreased after 5 weeks. These data suggest that genetically engineered macrophage transplantation may be a very useful form of <jats:italic>ex vivo<\/jats:italic> gene therapy for lysosomal storage diseases. We also discuss the possible treatment of the CNS involvement in lysosomal storage diseases by gene therapy\/cell therapy.<\/jats:p>","DOI":"10.1023\/a:1005692215317","type":"journal-article","created":{"date-parts":[[2002,12,21]],"date-time":"2002-12-21T23:07:17Z","timestamp":1040512037000},"page":"293-298","source":"Crossref","is-referenced-by-count":6,"title":["Gene therapy\/cell therapy for lysosomal storage disease"],"prefix":"10.1002","volume":"23","author":[{"given":"Y.","family":"Eto","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Institute for DNA Medicine Tokyo Jikei University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Gene Therapy, Institute for DNA Medicine Tokyo Jikei University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2000,5]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2296"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950019219"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.17-2629"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.11.6474"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)91046-1"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1095-1017"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.4.1358.1358"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0693-154"},{"key":"e_1_2_1_10_1","first-page":"2465","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Neufeld EF","year":"1995"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.4.1287"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1998.tb01708.x"},{"key":"e_1_2_1_13_1","doi-asserted-by":"crossref","unstructured":"OhashiT YokooT IizukaS KobayashiH SlyWS EtoY(2000)Reduction of lysosomalstorage in murine mucopolysaccharidosis type VII by transplantation of normal andgenetically modified macrophages.Blood(in press)..","DOI":"10.1182\/blood.V95.11.3631"},{"key":"e_1_2_1_14_1","first-page":"711","article-title":"Construction of non\u2010defectiveadenovirus type 5 bearing a 2.8\u2010kilobase hepatitis B virus DNA near the right end of its genome","volume":"54","author":"Saito I","year":"1985","journal-title":"J V irol"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/374367a0"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300775"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1023%2FA%3A1005692215317","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1023\/A%3A1005692215317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T23:37:06Z","timestamp":1694821026000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1023\/A%3A1005692215317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,5]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2000,5]]}},"alternative-id":["10.1023\/A:1005692215317"],"URL":"https:\/\/doi.org\/10.1023\/a:1005692215317","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,5]]}}}