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@ARTICLE{Venkatesan:276216,
      author       = {V. Venkatesan and A. C. Christopher and M. Rhiel and M. K.
                      K. Azhagiri and P. Babu and K. Walavalkar and B. Saravanan
                      and G. Andrieux$^*$ and S. Rangaraj and S. Srinivasan and K.
                      V. Karuppusamy and A. Jacob and A. Bagchi and A. A. Pai and
                      Y. Nakamura and R. Kurita and P. Balasubramanian and R. Pai
                      and S. K. Marepally and K. M. Mohankumar and S. R.
                      Velayudhan and M. Börries$^*$ and D. Notani and T. Cathomen
                      and A. Srivastava and S. Thangavel},
      title        = {{E}diting the core region in {HPFH} deletions alters fetal
                      and adult globin expression for treatment of
                      β-hemoglobinopathies.},
      journal      = {Molecular Therapy / Nucleic Acids},
      volume       = {32},
      issn         = {2162-2531},
      address      = {New York, NY},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2023-01028},
      pages        = {671 - 688},
      year         = {2023},
      abstract     = {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 in vivo. Furthermore, PRR-βE1 gene editing
                      is feasible without ex vivo HSPC culture. Importantly, the
                      editing induced therapeutically significant levels of HbF to
                      reverse the phenotypes of both sickle cell disease and
                      β-thalassemia major. These findings imply that PRR-βE1
                      gene editing of patient HSPCs could lead to improved
                      therapeutic outcomes for β-hemoglobinopathy gene therapy.},
      keywords     = {HPFH mutation (Other) / MT: RNA/DNA Editing (Other) /
                      beta-thalassemia (Other) / deletional HPFH (Other) / fetal
                      hemoglobin (Other) / gene editing (Other) / gene therapy
                      (Other) / hematopoietic stem cells (Other) / large deletions
                      (Other) / locus control region. (Other) / sickle cell
                      diseases (Other)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37215154},
      pmc          = {pmc:PMC10197010},
      doi          = {10.1016/j.omtn.2023.04.024},
      url          = {https://inrepo02.dkfz.de/record/276216},
}