Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia

Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Dian Lu [verfasserIn] Zhiliang Xu [verfasserIn] Zhiyong Peng [verfasserIn] Yinghong Yang [verfasserIn] Bing Song [verfasserIn] Zeyu Xiong [verfasserIn] Zhirui Ma [verfasserIn] Hongmei Guan [verfasserIn] Bangzhu Chen [verfasserIn] Yukio Nakamura [verfasserIn] Juan Zeng [verfasserIn] Nengqing Liu [verfasserIn] Xiaofang Sun [verfasserIn] Diyu Chen [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	fetal hemoglobin (HbF) hereditary persistence of fetal hemoglobin (HPFH) thalassemia genome editing adeno-associated virus (AAV)

Übergeordnetes Werk:	In: Frontiers in Genetics - Frontiers Media S.A., 2011, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fgene.2022.881937

Katalog-ID:	DOAJ043695094

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allfieldsGer	10.3389/fgene.2022.881937 doi (DE-627)DOAJ043695094 (DE-599)DOAJ9670f5472db7477fb9b99dfdbfa72249 DE-627 ger DE-627 rakwb eng QH426-470 Dian Lu verfasserin aut Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C > G, and −198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for β-thalassemia. fetal hemoglobin (HbF) hereditary persistence of fetal hemoglobin (HPFH) thalassemia genome editing adeno-associated virus (AAV) Genetics Zhiliang Xu verfasserin aut Zhiyong Peng verfasserin aut Yinghong Yang verfasserin aut Bing Song verfasserin aut Zeyu Xiong verfasserin aut Zhirui Ma verfasserin aut Hongmei Guan verfasserin aut Bangzhu Chen verfasserin aut Yukio Nakamura verfasserin aut Juan Zeng verfasserin aut Nengqing Liu verfasserin aut Xiaofang Sun verfasserin aut Diyu Chen verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 13(2022) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:13 year:2022 https://doi.org/10.3389/fgene.2022.881937 kostenfrei https://doaj.org/article/9670f5472db7477fb9b99dfdbfa72249 kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2022.881937/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
allfieldsSound	10.3389/fgene.2022.881937 doi (DE-627)DOAJ043695094 (DE-599)DOAJ9670f5472db7477fb9b99dfdbfa72249 DE-627 ger DE-627 rakwb eng QH426-470 Dian Lu verfasserin aut Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C > G, and −198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for β-thalassemia. fetal hemoglobin (HbF) hereditary persistence of fetal hemoglobin (HPFH) thalassemia genome editing adeno-associated virus (AAV) Genetics Zhiliang Xu verfasserin aut Zhiyong Peng verfasserin aut Yinghong Yang verfasserin aut Bing Song verfasserin aut Zeyu Xiong verfasserin aut Zhirui Ma verfasserin aut Hongmei Guan verfasserin aut Bangzhu Chen verfasserin aut Yukio Nakamura verfasserin aut Juan Zeng verfasserin aut Nengqing Liu verfasserin aut Xiaofang Sun verfasserin aut Diyu Chen verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 13(2022) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:13 year:2022 https://doi.org/10.3389/fgene.2022.881937 kostenfrei https://doaj.org/article/9670f5472db7477fb9b99dfdbfa72249 kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2022.881937/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022
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authorswithroles_txt_mv	Dian Lu @@aut@@ Zhiliang Xu @@aut@@ Zhiyong Peng @@aut@@ Yinghong Yang @@aut@@ Bing Song @@aut@@ Zeyu Xiong @@aut@@ Zhirui Ma @@aut@@ Hongmei Guan @@aut@@ Bangzhu Chen @@aut@@ Yukio Nakamura @@aut@@ Juan Zeng @@aut@@ Nengqing Liu @@aut@@ Xiaofang Sun @@aut@@ Diyu Chen @@aut@@
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callnumber-first	Q - Science
author	Dian Lu
spellingShingle	Dian Lu misc QH426-470 misc fetal hemoglobin (HbF) misc hereditary persistence of fetal hemoglobin (HPFH) misc thalassemia misc genome editing misc adeno-associated virus (AAV) misc Genetics Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia
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topic_title	QH426-470 Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia fetal hemoglobin (HbF) hereditary persistence of fetal hemoglobin (HPFH) thalassemia genome editing adeno-associated virus (AAV)
topic	misc QH426-470 misc fetal hemoglobin (HbF) misc hereditary persistence of fetal hemoglobin (HPFH) misc thalassemia misc genome editing misc adeno-associated virus (AAV) misc Genetics
topic_unstemmed	misc QH426-470 misc fetal hemoglobin (HbF) misc hereditary persistence of fetal hemoglobin (HPFH) misc thalassemia misc genome editing misc adeno-associated virus (AAV) misc Genetics
topic_browse	misc QH426-470 misc fetal hemoglobin (HbF) misc hereditary persistence of fetal hemoglobin (HPFH) misc thalassemia misc genome editing misc adeno-associated virus (AAV) misc Genetics
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title	Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia
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title_full	Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia
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author_browse	Dian Lu Zhiliang Xu Zhiyong Peng Yinghong Yang Bing Song Zeyu Xiong Zhirui Ma Hongmei Guan Bangzhu Chen Yukio Nakamura Juan Zeng Nengqing Liu Xiaofang Sun Diyu Chen
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title_sort	induction of fetal hemoglobin by introducing natural hereditary persistence of fetal hemoglobin mutations in the γ-globin gene promoters for genome editing therapies for β-thalassemia
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title_auth	Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia
abstract	Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C > G, and −198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for β-thalassemia.
abstractGer	Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C > G, and −198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for β-thalassemia.
abstract_unstemmed	Reactivation of γ-globin expression is a promising therapeutic approach for β-hemoglobinopathies. Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A > G, −114C > T, −117G>A, −175T > C, −195C > G, and −198T > C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. This study provides evidence of the effectiveness of introducing naturally occurring HPFH mutations as a genetic therapy for β-thalassemia.
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title_short	Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia
url	https://doi.org/10.3389/fgene.2022.881937 https://doaj.org/article/9670f5472db7477fb9b99dfdbfa72249 https://www.frontiersin.org/articles/10.3389/fgene.2022.881937/full https://doaj.org/toc/1664-8021
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author2	Zhiliang Xu Zhiyong Peng Yinghong Yang Bing Song Zeyu Xiong Zhirui Ma Hongmei Guan Bangzhu Chen Yukio Nakamura Juan Zeng Nengqing Liu Xiaofang Sun Diyu Chen
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doi_str	10.3389/fgene.2022.881937
callnumber-a	QH426-470
up_date	2024-07-03T18:58:07.421Z
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Here, we propose a novel Cas9/AAV6-mediated genome editing strategy for the treatment of β-thalassemia: Natural HPFH mutations −113A &gt; G, −114C &gt; T, −117G&gt;A, −175T &gt; C, −195C &gt; G, and −198T &gt; C were introduced by homologous recombination following disruption of BCL11A binding sites in HBG1/HBG2 promoters. Precise on-target editing and significantly increased γ-globin expression during erythroid differentiation were observed in both HUDEP-2 cells and primary HSPCs from β-thalassemia major patients. Moreover, edited HSPCs maintained the capacity for long-term hematopoietic reconstitution in B-NDG hTHPO mice. 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Induction of Fetal Hemoglobin by Introducing Natural Hereditary Persistence of Fetal Hemoglobin Mutations in the γ-Globin Gene Promoters for Genome Editing Therapies for β-Thalassemia

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