{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T01:16:01Z","timestamp":1755998161569},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T00:00:00Z","timestamp":1224028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Purine nucleoside phosphorylase (PNP) deficiency causes the accumulation of toxic purine metabolites and lethal T cell immune defects, which might be corrected by expressing PNP by transplanting bone marrow (BM) cells transduced with lentiviral vectors containing the human PNP gene (lentiPNP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lymphocytes from a single PNP\u2010deficient patient as well as lymphocytes, fibroblasts and BM from PNP\u2010deficient (PNP \u2212 \/\u2212) mice were transduced with lentiPNP. Female PNP \u2212 \/\u2212 mice were transplanted with lentiPNP transduced BM cells from male PNP \u2212 \/\u2212 mice or normal BM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LentiPNP transduction significantly increased PNP expression in PNP\u2010deficient human lymphocytes, murine lymphocytes, fibroblasts and BM cells. LentiPNP transduction also significantly improved the proliferation of PNP \u2212 \/\u2212 murine lymphocyte and survival of irradiated PNP \u2212 \/\u2212 fibroblasts. Polymerase chain reaction analysis demonstrated efficient transduction of lentiPNP into total and lineage\u2010depleted BM cells grown <jats:italic>ex vivo<\/jats:italic>. LentiPNP transduced PNP \u2212 \/\u2212 BM cells transplanted into PNP \u2212 \/\u2212 mice expressed PNP <jats:italic>in vivo<\/jats:italic>, partially restored urinary uric acid secretion, improved thymocytes maturation, increased weight gain and extended survival of the mice. However, 12 weeks after transplant, the benefit of lentiPNP transduced cells and normal BM diminished and the percentage of engrafted donor cells decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This short\u2010term observational study provides the first <jats:italic>in vivo<\/jats:italic> proof that gene therapy may correct some of the abnormalities associated with PNP deficiency. Better gene transduction and expression, as well as improved cell engraftment, are required to further advance PNP gene therapy. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1261","type":"journal-article","created":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T08:09:00Z","timestamp":1224058140000},"page":"1282-1293","source":"Crossref","is-referenced-by-count":15,"title":["Lentivirus gene therapy for purine nucleoside phosphorylase deficiency"],"prefix":"10.1002","volume":"10","author":[{"given":"Pu","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Toro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixian","family":"Min","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaim M.","family":"Roifman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyal","family":"Grunebaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,10,15]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"143","volume-title":"Primary T\u2010cell Immunodeficiency","author":"Cohen A","year":"2001"},{"key":"e_1_2_6_3_2","first-page":"45","article-title":"Purine nucleoside phosphorylase deficiency","volume":"3","author":"Markert ML","year":"1991","journal-title":"Immunodefic Rev"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.06.075"},{"key":"e_1_2_6_5_2","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1001\/jama.295.5.508","article-title":"Bone marrow transplant from matched unrelated donors in severe combined immune deficiency","volume":"295","author":"Grunebaum E","year":"2006","journal-title":"JAMA"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.12.2197"},{"key":"e_1_2_6_7_2","first-page":"1411","article-title":"Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology","volume":"23","author":"Dror Y","year":"2004","journal-title":"Pediatr Res"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25052"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2005.07.006"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.03.059"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.4049\/jimmunol.154.6.3006","article-title":"Correction of proliferative responses in purine nucleoside phosphorylase (PNP)\u2010deficient T lymphocytes by retroviral\u2010mediated PNP gene transfer","volume":"154","author":"Nelson DM","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2003.11.005"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-023507"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608130103"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.11.012"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2001.590608.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2006.07.003"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-023507"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00474-0"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-182-6_9"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1070104"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1698"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.17.6563"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-182-6_17"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2000.17802.x"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.02.013"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-103663"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0782"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2006.0057"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.1261","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.1261","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T19:05:57Z","timestamp":1699988757000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.1261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,15]]},"references-count":28,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["10.1002\/jgm.1261"],"URL":"https:\/\/doi.org\/10.1002\/jgm.1261","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"value":"1099-498X","type":"print"},{"value":"1521-2254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,15]]}}}