Gene Editing of the Human BCL11A Erythroid Enhancer for Treatment of the Haemoglobinopathies

Nature

BCL11A is a transcriptional repressor that inhibits expression of foetal globin genes in adults, and is a potential therapeutic target for the treatment of β-haemoglobinopathies, such as β-thalassaemia and sickle cell disease. The enhancer of BCL11A is subject to common genetic variation associated with foetal haemoglobin level. In a recent article published in journal Nature, Daniel Bauer, Stuart Orkin and colleagues used a CRISPR–Cas9 approach to perform saturation mutagenesis of the human and mouse BCL11A enhancers, producing a map that reveals critical regions and specific vulnerabilities. They validated BCL11A enhancer disruption by CRISPR–Cas9 as a therapeutic strategy for inducing foetal haemoglobin by applying it in both mice and primary human erythroblast cells. The discovery creates a path for developing gene editing approaches for treating sickle cell disease and other haemoglobin disorders.

More information: Nature article