{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:38:27Z","timestamp":1791851907974,"version":"4.3.4"},"reference-count":42,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b2-Thalassemia intermedia is a disorder characterized by ineffective erythropoiesis (IE), anemia, splenomegaly, and systemic iron overload. Novel approaches are being explored based on the modulation of pathways that reduce iron absorption (ie, using hepcidin activators like Tmprss6-antisense oligonucleotides [ASOs]) or increase erythropoiesis (by erythropoietin [EPO] administration or modulating the ability of transferrin receptor 2 [Tfr2] to control red blood cell [RBC] synthesis). Targeting Tmprss6 messenger RNA by Tmprss6-ASO was proven to be effective in improving IE and splenomegaly by inducing iron restriction. However, we postulated that combinatorial strategies might be superior to single therapies. Here, we combined Tmprss6-ASO with EPO administration or removal of a single Tfr2 allele in the bone marrow of animals affected by \u03b2-thalassemia intermedia (Hbbth3\/+). EPO administration alone or removal of a single Tfr2 allele increased hemoglobin levels and RBCs. However, EPO or Tfr2 single-allele deletion alone, respectively, exacerbated or did not improve splenomegaly in \u03b2-thalassemic mice. To overcome this issue, we postulated that some level of iron restriction (by targeting Tmprss6) would improve splenomegaly while preserving the beneficial effects on RBC production mediated by EPO or Tfr2 deletion. While administration of Tmprss6-ASO alone improved the anemia, the combination of Tmprss6-ASO + EPO or Tmprss6-ASO + Tfr2 single-allele deletion produced significantly higher hemoglobin levels and reduced splenomegaly. In conclusion, our results clearly indicate that these combinatorial approaches are superior to single treatments in ameliorating IE and anemia in \u03b2-thalassemia and could provide guidance to translate some of these approaches into viable therapies.<\/jats:p>","DOI":"10.1182\/blood.2019004719","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T17:59:26Z","timestamp":1592416766000},"page":"1968-1979","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["Correcting \u03b2-thalassemia by combined therapies that restrict iron and modulate erythropoietin activity"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8458-1786","authenticated-orcid":false,"given":"Carla","family":"Casu","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3259-4865","authenticated-orcid":false,"given":"Mariateresa","family":"Pettinato","sequence":"additional","affiliation":[{"name":"Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy;"},{"name":"Vita-Salute San Raffaele University, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Aghajan","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Inc, Carlsbad, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vania","family":"Lo Presti","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3413-8414","authenticated-orcid":false,"given":"Maria Rosa","family":"Lidonnici","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Munoz","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emir","family":"O\u2019Hara","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-6706","authenticated-orcid":false,"given":"Violante","family":"Olivari","sequence":"additional","affiliation":[{"name":"Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy;"},{"name":"Vita-Salute San Raffaele University, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-2146","authenticated-orcid":false,"given":"Simona Maria","family":"Di Modica","sequence":"additional","affiliation":[{"name":"Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy;"},{"name":"Vita-Salute San Raffaele University, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri","family":"Booten","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Inc, Carlsbad, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuling","family":"Guo","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Inc, Carlsbad, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"Neil","sequence":"additional","affiliation":[{"name":"Aevi Genomic Medicine, Inc, Wayne, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Miari","sequence":"additional","affiliation":[{"name":"Medgenics Medical Israel, Ltd, Misgav Dov, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Shapir","sequence":"additional","affiliation":[{"name":"Medgenics Medical Israel, Ltd, Misgav Dov, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbal","family":"Zafir-Lavie","sequence":"additional","affiliation":[{"name":"Aevi Genomic Medicine, Inc, Wayne, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Domev","sequence":"additional","affiliation":[{"name":"Medgenics Medical Israel, Ltd, Misgav Dov, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-3133","authenticated-orcid":false,"given":"Giuliana","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, Milan, Italy;"},{"name":"San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Sitara","sequence":"additional","affiliation":[{"name":"Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0739-5282","authenticated-orcid":false,"given":"Antonella","family":"Nai","sequence":"additional","affiliation":[{"name":"Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy;"},{"name":"Vita-Salute San Raffaele University, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0938-6558","authenticated-orcid":false,"given":"Stefano","family":"Rivella","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Perelman School of Medicine and"},{"name":"Cell and Molecular Biology Affinity Group, University of Pennsylvania, Philadelphia, PA; and"},{"name":"Raymond G. Perelman Center for Cellular and Molecular Therapeutics, and"},{"name":"Penn Center for Musculoskeletal Disorders, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"2","key":"2020102211274300000_B1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.blre.2017.10.001","article-title":"What can we learn from ineffective erythropoiesis in thalassemia?","volume":"32","author":"Oikonomidou","year":"2018","journal-title":"Blood Rev"},{"issue":"10116","key":"2020102211274300000_B2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0140-6736(17)31822-6","article-title":"Thalassaemia","volume":"391","author":"Taher","year":"2017","journal-title":"Lancet"},{"issue":"4","key":"2020102211274300000_B3","doi-asserted-by":"crossref","first-page":"418","DOI":"10.3324\/haematol.2014.114827","article-title":"\u03b2-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies","volume":"100","author":"Rivella","year":"2015","journal-title":"Haematologica"},{"issue":"1","key":"2020102211274300000_B4","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1182\/blood-2018-07-815928","article-title":"Iron metabolism under conditions of ineffective erythropoiesis in \u03b2-thalassemia","volume":"133","author":"Rivella","year":"2019","journal-title":"Blood"},{"issue":"2","key":"2020102211274300000_B5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.hoc.2017.11.009","article-title":"Ineffective erythropoiesis: anemia and iron overload","volume":"32","author":"Gupta","year":"2018","journal-title":"Hematol Oncol Clin North Am"},{"issue":"11","key":"2020102211274300000_B6","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1182\/blood.V79.11.3007.3007","article-title":"Isolation, characterization, and immunoprecipitation studies of immune complexes from membranes of beta-thalassemic erythrocytes","volume":"79","author":"Yuan","year":"1992","journal-title":"Blood"},{"issue":"1","key":"2020102211274300000_B7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1749-6632.1969.tb27787.x","article-title":"Formation of hemichromes from oxidized hemoglobin subunits","volume":"165","author":"Rachmilewitz","year":"1969","journal-title":"Ann N Y Acad Sci"},{"key":"2020102211274300000_B8","doi-asserted-by":"crossref","first-page":"938640","DOI":"10.1155\/2010\/938640","article-title":"Beta-thalassemia: HiJAKing ineffective erythropoiesis and iron overload","volume":"2010","author":"Melchiori","year":"2010","journal-title":"Adv Hematol"},{"issue":"3","key":"2020102211274300000_B9","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/bjh.13875","article-title":"Cell cycle, proliferation and apoptosis in erythroblasts cultured from patients with \u03b2-thalassaemia major","volume":"175","author":"Forster","year":"2016","journal-title":"Br J Haematol"},{"issue":"17","key":"2020102211274300000_B10","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1182\/blood-2015-07-658419","article-title":"Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of \u03b2-thalassemia","volume":"126","author":"Kautz","year":"2015","journal-title":"Blood"},{"issue":"7","key":"2020102211274300000_B11","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/ng.2996","article-title":"Identification of erythroferrone as an erythroid regulator of iron metabolism [published correction appears in Nat Genet. 2020;52(4):463]","volume":"46","author":"Kautz","year":"2014","journal-title":"Nat Genet"},{"issue":"50","key":"2020102211274300000_B12","doi-asserted-by":"crossref","first-page":"E4922","DOI":"10.1073\/pnas.1314197110","article-title":"Intestinal HIF2\u03b1 promotes tissue-iron accumulation in disorders of iron overload with anemia","volume":"110","author":"Anderson","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"issue":"12","key":"2020102211274300000_B13","doi-asserted-by":"crossref","first-page":"E2778","DOI":"10.3390\/ijms18122778","article-title":"Iron overload and chelation therapy in non-transfusion dependent thalassemia","volume":"18","author":"Bou-Fakhredin","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2020102211274300000_B14","doi-asserted-by":"crossref","first-page":"E182","DOI":"10.3390\/ijms19010182","article-title":"Non-transfusion-dependent thalassemia: an update on complications and management","volume":"19","author":"Sleiman","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2020102211274300000_B15","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.3324\/haematol.2015.133348","article-title":"Combination of Tmprss6- ASO and the iron chelator deferiprone improves erythropoiesis and reduces iron overload in a mouse model of beta-thalassemia intermedia","volume":"101","author":"Casu","year":"2016","journal-title":"Haematologica"},{"key":"2020102211274300000_B16","first-page":"haematol.2018.212589","article-title":"Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult beta-thalassemia major","author":"Casu","year":"2019","journal-title":"Haematologica"},{"issue":"2","key":"2020102211274300000_B17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1182\/blood-2015-10-676742","article-title":"Minihepcidin peptides as disease modifiers in mice affected by \u03b2-thalassemia and polycythemia vera","volume":"128","author":"Casu","year":"2016","journal-title":"Blood"},{"issue":"4","key":"2020102211274300000_B18","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1172\/JCI66969","article-title":"Reducing TMPRSS6 ameliorates hemochromatosis and \u03b2-thalassemia in mice","volume":"123","author":"Guo","year":"2013","journal-title":"J Clin Invest"},{"issue":"7","key":"2020102211274300000_B19","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood-2012-09-453977","article-title":"An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-\/-) mice and ameliorates anemia and iron overload in murine \u03b2-thalassemia intermedia","volume":"121","author":"Schmidt","year":"2013","journal-title":"Blood"},{"issue":"9","key":"2020102211274300000_B20","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.3324\/haematol.2018.209874","article-title":"New thiazolidinones reduce iron overload in mouse models of hereditary hemochromatosis and \u03b2-thalassemia","volume":"104","author":"Liu","year":"2019","journal-title":"Haematologica"},{"issue":"1","key":"2020102211274300000_B21","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1172\/JCI129382","article-title":"Oral ferroportin inhibitor ameliorates ineffective erythropoiesis in a model of \u03b2-thalassemia","volume":"130","author":"Manolova","year":"2019","journal-title":"J Clin Invest"},{"issue":"4","key":"2020102211274300000_B22","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ajh.23934","article-title":"Combination therapy with a Tmprss6 RNAi-therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of \u03b2-thalassemia intermedia","volume":"90","author":"Schmidt","year":"2015","journal-title":"Am J Hematol"},{"issue":"21","key":"2020102211274300000_B23","doi-asserted-by":"crossref","first-page":"5021","DOI":"10.1182\/blood-2012-01-401885","article-title":"Deletion of TMPRSS6 attenuates the phenotype in a mouse model of \u03b2-thalassemia","volume":"119","author":"Nai","year":"2012","journal-title":"Blood"},{"issue":"4","key":"2020102211274300000_B24","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1089\/humc.2015.125","article-title":"Preclinical and preliminary clinical evaluation of genetically transduced dermal tissue implants for the sustained secretion of erythropoietin and interferon \u03b1","volume":"26","author":"Shapir","year":"2015","journal-title":"Hum Gene Ther Clin Dev"},{"issue":"21","key":"2020102211274300000_B25","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1182\/blood-2018-05-852277","article-title":"Transferrin receptor 2 is a potential novel therapeutic target for \u03b2-thalassemia: evidence from a murine model [published correction appears in Blood. 2019;134(1):94]","volume":"132","author":"Artuso","year":"2018","journal-title":"Blood"},{"issue":"7","key":"2020102211274300000_B26","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1182\/blood-2014-08-596254","article-title":"The second transferrin receptor regulates red blood cell production in mice","volume":"125","author":"Nai","year":"2015","journal-title":"Blood"},{"issue":"6","key":"2020102211274300000_B27","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.3324\/haematol.2013.103143","article-title":"The erythroid function of transferrin receptor 2 revealed by Tmprss6 inactivation in different models of transferrin receptor 2 knockout mice","volume":"99","author":"Nai","year":"2014","journal-title":"Haematologica"},{"key":"2020102211274300000_B28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3389\/fphar.2014.00093","article-title":"The extrahepatic role of TFR2 in iron homeostasis","volume":"5","author":"Silvestri","year":"2014","journal-title":"Front Pharmacol"},{"issue":"25","key":"2020102211274300000_B29","doi-asserted-by":"crossref","first-page":"11608","DOI":"10.1073\/pnas.92.25.11608","article-title":"A mouse model for beta 0-thalassemia","volume":"92","author":"Yang","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"issue":"16","key":"2020102211274300000_B30","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1182\/blood-2009-09-240960","article-title":"Comparison of 3 Tfr2-deficient murine models suggests distinct functions for Tfr2-alpha and Tfr2-beta isoforms in different tissues","volume":"115","author":"Roetto","year":"2010","journal-title":"Blood"},{"issue":"1","key":"2020102211274300000_B31","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1089\/nat.2018.0753","article-title":"integrated assessment of the clinical performance of galnac3-conjugated 2\u2032-o-methoxyethyl chimeric antisense oligonucleotides: I. Human volunteer experience","volume":"29","author":"Crooke","year":"2019","journal-title":"Nucleic Acid Ther"},{"issue":"13","key":"2020102211274300000_B32","doi-asserted-by":"crossref","first-page":"8796","DOI":"10.1093\/nar\/gku531","article-title":"Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice","volume":"42","author":"Prakash","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"2020102211274300000_B33","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1084\/jem.20170396","article-title":"Iron modulation of erythropoiesis is associated with Scribble-mediated control of the erythropoietin receptor","volume":"215","author":"Khalil","year":"2018","journal-title":"J Exp Med"},{"key":"2020102211274300000_B34","doi-asserted-by":"crossref","first-page":"978710","DOI":"10.1155\/2010\/978710","article-title":"The antioxidant effect of erythropoietin on thalassemic blood cells","volume":"2010","author":"Amer","year":"2010","journal-title":"Anemia"},{"issue":"255","key":"2020102211274300000_B35","first-page":"86","article-title":"Clinical application of recombinant erythropoietin in beta-thalassaemia intermedia","author":"Asadov","year":"2016","journal-title":"Georgian Med News"},{"issue":"1","key":"2020102211274300000_B36","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1600-0609.1997.tb01405.x","article-title":"Administration of high doses of recombinant human erythropoietin to patients with beta-thalassemia intermedia: a preliminary trial","volume":"58","author":"Bourantas","year":"1997","journal-title":"Eur J Haematol"},{"issue":"4","key":"2020102211274300000_B37","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1159\/000077551","article-title":"Treatment of beta-thalassemia patients with recombinant human erythropoietin: effect on transfusion requirements and soluble adhesion molecules","volume":"111","author":"Chaidos","year":"2004","journal-title":"Acta Haematol"},{"issue":"6","key":"2020102211274300000_B38","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1093\/tropej\/42.6.330","article-title":"Recombinant human erythropoietin trial in thalassemia intermedia","volume":"42","author":"Ni\u015fli","year":"1996","journal-title":"J Trop Pediatr"},{"issue":"12","key":"2020102211274300000_B39","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1182\/blood.V80.12.3258.3258","article-title":"Trial of recombinant human erythropoietin: three patients with thalassemia intermedia","volume":"80","author":"Olivieri","year":"1992","journal-title":"Blood"},{"issue":"1 COOLEY\u2019S ANEM","key":"2020102211274300000_B40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1749-6632.1998.tb10470.x","article-title":"The role of recombinant human erythropoietin in the treatment of thalassemia","volume":"850","author":"Rachmilewitz","year":"1998","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"2020102211274300000_B41","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1365-2141.2007.06654.x","article-title":"Modern treatment of thalassaemia intermedia","volume":"138","author":"Borgna-Pignatti","year":"2007","journal-title":"Br J Haematol"},{"issue":"suppl 6","key":"2020102211274300000_B42","first-page":"S36","article-title":"Adverse events of erythropoietin in long-term and in acute\/short-term treatment","volume":"72","author":"Singbartl","year":"1994","journal-title":"Clin Investig"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/136\/17\/1968\/1778050\/bloodbld2019004719.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/136\/17\/1968\/1778050\/bloodbld2019004719.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T11:28:47Z","timestamp":1603366127000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/136\/17\/1968\/461017\/Correcting-%CE%B2thalassemia-by-combined-therapies-that"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,22]]},"references-count":42,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2020,10,22]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2019004719","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,22]]}}}