Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of β-hemoglobinopathies.
HPFH mutation
MT: RNA/DNA Editing
beta-thalassemia
deletional HPFH
fetal hemoglobin
gene editing
gene therapy
hematopoietic stem cells
large deletions
locus control region.
sickle cell diseases
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
13 Jun 2023
13 Jun 2023
Historique:
received:
17
12
2022
accepted:
24
04
2023
medline:
22
5
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
Reactivation of fetal hemoglobin (HbF) is a commonly adapted strategy to ameliorate β-hemoglobinopathies. However, the continued production of defective adult hemoglobin (HbA) limits HbF tetramer production affecting the therapeutic benefits. Here, we evaluated deletional hereditary persistence of fetal hemoglobin (HPFH) mutations and identified an 11-kb sequence, encompassing putative repressor region (PRR) to β-globin exon-1 (βE1), as the core deletion that ablates HbA and exhibits superior HbF production compared with HPFH or other well-established targets. PRR-βE1-edited hematopoietic stem and progenitor cells (HSPCs) retained their genome integrity and their engraftment potential to repopulate for long-term hematopoiesis in immunocompromised mice producing HbF positive cells
Identifiants
pubmed: 37215154
doi: 10.1016/j.omtn.2023.04.024
pii: S2162-2531(23)00110-5
pmc: PMC10197010
doi:
Types de publication
Journal Article
Langues
eng
Pagination
671-688Informations de copyright
© 2023 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
Br J Haematol. 2018 Mar;180(5):630-643
pubmed: 29193029
Mutat Res. 2003 Jan 10;534(1-2):65-75
pubmed: 12504755
Nat Commun. 2021 Aug 17;12(1):4991
pubmed: 34404810
Genet Med. 2017 Jun;19(6):609-619
pubmed: 27811859
Blood. 2022 Apr 7;139(14):2107-2118
pubmed: 35090172
J Vis Exp. 2022 Aug 9;(186):
pubmed: 36036597
Nat Genet. 2021 Jun;53(6):895-905
pubmed: 33846636
Blood Cells Mol Dis. 2009 Jul-Aug;43(1):53-7
pubmed: 19269866
Nat Med. 2020 Apr;26(4):535-541
pubmed: 32284612
Mol Genet Genomic Med. 2019 Jun;7(6):e680
pubmed: 30968607
Nat Methods. 2012 Oct;9(10):969-72
pubmed: 22961246
Blood. 1990 Feb 15;75(4):1000-5
pubmed: 1689188
Haematologica. 2021 Oct 01;106(10):2707-2719
pubmed: 32855279
Br J Haematol. 1993 Sep;85(1):143-7
pubmed: 8251381
J Med Genet. 1984 Aug;21(4):263-7
pubmed: 6208362
Proc Natl Acad Sci U S A. 2016 Sep 20;113(38):10661-5
pubmed: 27601644
Nature. 2016 Jan 28;529(7587):490-5
pubmed: 26735016
Mol Cell Biol. 2020 Dec 21;41(1):
pubmed: 33077498
Blood. 2012 Jan 12;119(2):364-7
pubmed: 22096240
Mol Ther. 2022 Jan 5;30(1):145-163
pubmed: 34418541
N Engl J Med. 2021 Jan 21;384(3):252-260
pubmed: 33283989
Blood Adv. 2019 Nov 12;3(21):3379-3392
pubmed: 31698466
Hum Gene Ther Methods. 2018 Feb;29(1):60-74
pubmed: 29325430
J Clin Med. 2020 Nov 23;9(11):
pubmed: 33238542
Cell Stem Cell. 2021 Jun 3;28(6):1136-1147.e5
pubmed: 33626327
Hum Genet. 2010 Mar;127(3):303-14
pubmed: 20183929
Int J Hematol. 2006 Apr;83(3):229-37
pubmed: 16720553
Cell Rep. 2020 Aug 4;32(5):107993
pubmed: 32755585
Stem Cell Reports. 2015 Feb 10;4(2):171-80
pubmed: 25601207
Appl Clin Genet. 2014 Dec 10;7:253-8
pubmed: 25525381
Blood. 2018 Nov 1;132(18):1963-1973
pubmed: 30150205
N Engl J Med. 2021 Jan 21;384(3):205-215
pubmed: 33283990
Front Immunol. 2022 Mar 14;13:792684
pubmed: 35359982
Blood. 2018 Apr 26;131(17):1960-1973
pubmed: 29519807
Nat Commun. 2017 Mar 14;8:14750
pubmed: 28290447
Mediterr J Hematol Infect Dis. 2017 Feb 20;9(1):e2017018
pubmed: 28293406
Hum Gene Ther. 2022 Feb;33(3-4):188-201
pubmed: 34486377
Nature. 2015 Nov 12;527(7577):192-7
pubmed: 26375006
Blood. 1988 Feb;71(2):457-62
pubmed: 2827815
Methods Mol Biol. 2019;2031:79-104
pubmed: 31473955
Hugo J. 2009 Dec;3(1-4):51-62
pubmed: 21119755
Nature. 2014 Oct 9;514(7521):242-6
pubmed: 25156257
Biochem Biophys Res Commun. 2021 May 7;552:157-163
pubmed: 33744764
Annu Rev Pathol. 2019 Jan 24;14:263-292
pubmed: 30332562
PLoS One. 2015 Nov 17;10(11):e0141706
pubmed: 26576059
Sci Rep. 2020 Jun 23;10(1):10133
pubmed: 32576837
Sci Transl Med. 2019 Jul 31;11(503):
pubmed: 31366580
Biochem Genet. 1977 Dec;15(11-12):1083-96
pubmed: 603615
Blood. 1988 Aug;72(2):636-41
pubmed: 2456798
Mol Ther Methods Clin Dev. 2017 Jan 11;4:137-148
pubmed: 28344999
PLoS One. 2019 Jan 15;14(1):e0208237
pubmed: 30645582
Science. 2016 Jan 15;351(6270):285-9
pubmed: 26816381