{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T01:18:50Z","timestamp":1794100730846,"version":"4.8.0"},"reference-count":54,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,3,15]]},"abstract":"<jats:p>Increased fetal hemoglobin (HbF) levels diminish the clinical severity of \u03b2-thalassemia and sickle cell anemia. A treatment strategy using autologous stem cell\u2013targeted gene transfer of a \u03b3-globin gene may therefore have therapeutic potential. We evaluated oncoretroviral- and lentiviral-based \u03b3-globin vectors for expression in transduced erythroid cell lines. Compared with \u03b3-globin, oncoretroviral vectors containing either a \u03b2-spectrin or \u03b2-globin promoter and the \u03b1-globin HS40 element, a \u03b3-globin lentiviral vector utilizing the \u03b2-globin promoter and elements from the \u03b2-globin locus control region demonstrated a higher probability of expression. This lentiviral vector design was evaluated in lethally irradiated mice that received transplants of transduced bone marrow cells. Long-term, stable erythroid expression of human \u03b3-globin was observed with levels of vector-encoded \u03b3-globin mRNA ranging from 9% to 19% of total murine \u03b1-globin mRNA. The therapeutic efficacy of the vector was subsequently evaluated in a murine model of \u03b2-thalassemia intermedia. The majority of mice that underwent transplantation expressed significant levels of chimeric m\u03b12h\u03b32molecules (termed HbF), the amount of which correlated with the degree of phenotypic improvement. A group of animals with a mean HbF level of 21% displayed a 2.5 g\/dL (25 g\/L) improvement in Hb concentration and normalization of erythrocyte morphology relative to control animals. \u03b3-Globin expression and phenotypic improvement was variably lower in other animals due to differences in vector copy number and chromosomal position effects. These data establish the potential of using a \u03b3-globin lentiviral vector for gene therapy of \u03b2-thalassemia.<\/jats:p>","DOI":"10.1182\/blood-2002-07-2211","type":"journal-article","created":{"date-parts":[[2003,2,27]],"date-time":"2003-02-27T18:28:53Z","timestamp":1046370533000},"page":"2175-2183","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":136,"title":["The degree of phenotypic correction of murine \u03b2-thalassemia intermedia following lentiviral-mediated transfer of a human \u03b3-globin gene is influenced by chromosomal position effects and vector copy number"],"prefix":"10.1182","volume":"101","author":[{"given":"Derek A.","family":"Persons","sequence":"first","affiliation":[{"name":"From the Division of Experimental Hematology, Department of Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip W.","family":"Hargrove","sequence":"additional","affiliation":[{"name":"From the Division of Experimental Hematology, Department of Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther R.","family":"Allay","sequence":"additional","affiliation":[{"name":"From the Division of Experimental Hematology, Department of Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Hanawa","sequence":"additional","affiliation":[{"name":"From the Division of Experimental Hematology, Department of Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur W.","family":"Nienhuis","sequence":"additional","affiliation":[{"name":"From the Division of Experimental Hematology, Department of Hematology and Oncology, St Jude 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