CRISPR-CAS 9 AND ITS APPLICATION AS THERAPEUTICS FOR β-HAEMOGLOBINOPATHIES

Abstract

CRISPR/Cas 9 is presently an excellent genome editing tool and is supposed to be instrumental in correcting several genetic diseases. Sickle cell disease (SCD) and β-thalassaemia are important genetic diseases that result from mutations in the β-globin (HBB) gene. Lentiviral-mediated gene therapy is an efficacious strategy for the treatment of β-hemoglobinopathies but is quite expensive with variable outcomes. Allogenic HSC transplantation from HLA-matched donors to treat betahemoglobinopathies is assessable to limited individuals due to the scarcity of immunologically matched donor sources. One of the strategies to treat β-hemoglobinopathies is the induction of high fetal hemoglobin (HbF) because it is known that high HbF levels are strongly linked with milder disease in SCD and β-thalassemia patients. Amidst several pros and cons of available therapies, CRISPR-mediated therapy is based either on the induction of HbF or correcting defective β-globin gene. The induction of HbF can be achieved by knocking down HbF repressors or editing HbF regulatory elements while the defective β-globin gene is corrected in patient HSPCs and iPSCs and then autologous transplantation is performed. CRISPR/Cas 9 offers an excellent opportunity for scientists in treating the β-hemoglobinopathies.

Keywords

• crispr/cas 9
• sickle cell disease
• β-thalassaemia
• fetal hemoglobin