Genome editing approaches to β-hemoglobinopathies

Prog Mol Biol Transl Sci. 2021;182:153-183. doi: 10.1016/bs.pmbts.2021.01.025. Epub 2021 Mar 1.


β-hemoglobinopathies are the most common monogenic disorders worldwide and are caused by mutations in the β-globin locus altering the production of adult hemoglobin (HbA). Transplantation of autologous hematopoietic stem cells (HSCs) corrected by lentiviral vector-mediated addition of a functional β-like globin raised new hopes to treat sickle cell disease and β-thalassemia patients; however, the low expression of the therapeutic gene per vector copy is often not sufficient to fully correct the patients with a severe clinical phenotype. Recent advances in the genome editing field brought new possibilities to cure β-hemoglobinopathies by allowing the direct modification of specific endogenous loci. Double-strand breaks (DSBs)-inducing nucleases (i.e., ZFNs, TALENs and CRISPR-Cas9) or DSB-free tools (i.e., base and prime editing) have been used to directly correct the disease-causing mutations, restoring HbA expression, or to reactivate the expression of the fetal hemoglobin (HbF), which is known to alleviate clinical symptoms of β-hemoglobinopathy patients. Here, we describe the different genome editing tools, their application to develop therapeutic approaches to β-hemoglobinopathies and ongoing clinical trials using genome editing strategies.

Trial registration: NCT04205435 NCT04211480 NCT03432364 NCT03653247 NCT03655678 NCT03745287.

Keywords: BCL11A enhancer; Fetal hemoglobin; Genome editing; HBG promoters; Sickle cell disease; β-Globin-gene correction; β-Thalassemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fetal Hemoglobin / genetics
  • Gene Editing
  • Hemoglobinopathies* / genetics
  • Hemoglobinopathies* / therapy
  • Humans
  • beta-Globins / genetics
  • beta-Thalassemia* / genetics
  • beta-Thalassemia* / therapy


  • beta-Globins
  • Fetal Hemoglobin

Associated data