Genome editing approaches to ß-hemoglobinopathies.
Prog Mol Biol Transl Sci
; 182: 153-183, 2021.
Article
em En
| MEDLINE
| ID: mdl-34175041
ß-hemoglobinopathies are the most common monogenic disorders worldwide and are caused by mutations in the ß-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 ß-like globin raised new hopes to treat sickle cell disease and ß-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 ß-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 ß-hemoglobinopathy patients. Here, we describe the different genome editing tools, their application to develop therapeutic approaches to ß-hemoglobinopathies and ongoing clinical trials using genome editing strategies.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Talassemia beta
/
Hemoglobinopatias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article