2023年4月17日 · Sickle-cell disease (SCD) is caused by an A·T-to-T·A transversion mutation in the β -globin gene (HBB). Here we show that prime editing can correct the SCD allele...

2021年1月29日 · CRISPR/Cas9-mediated beta-globin (HBB) gene correction of sickle cell disease (SCD) patient-derived hematopoietic stem cells (HSCs) in combination with autologous transplantation represents a...

Base editing of human HSPCs avoided the p53 activation and larger deletions that have been observed following Cas9 nuclease treatment. These findings point towards a one-time autologous treatment for SCD that eliminates pathogenic HBB S, generates benign HBB G, and minimizes the undesired consequences of double-strand DNA breaks.

Homozygosity (HbSS) is the most common genotype, resulting in sickle cell anemia (SCA), which is the most severe in the sickle cell disease (SCD) spectrum. Other forms are compound heterozygotes of HbS with other abnormal ß-chain variants, e.g., HbSC and HbSβ-thal.

Ex vivo delivery of mRNA encoding base editor with a targeting guide RNA into hematopoietic stem and progenitor cells (HSPCs) from SCD patients resulted in 80% HBB S-to-HBB G conversion. Sixteen weeks after transplantation of edited human HSPCs into immunodeficient mice, HBB G frequency was 68% and bone marrow reticulocytes demonstrated a 5 ...

2020年4月15日 · SCD is caused by a point mutation in human β-globin gene (HBB). Clinical strategies have demonstrated substantial success, however there is not any permanent cure for SCD available. CRISPR/Cas9 platform uses a single endonuclease and a single guide RNA (gRNA) to induce sequence-specific DNA double strand break (DSB).

Here, we demonstrate the preclinical feasibility, efficacy, and toxicology of HBB gene correction in plerixafor-mobilized CD34 + cells from healthy and SCD patient donors (gcHBB-SCD). We achieved up to 60% HBB allelic correction in clinical-scale gcHBB-SCD manufacturing.

SCD is autosomal recessive from a single point mutation in codon six of the β-globin gene (HBB) resulting in sickle hemoglobin. Ex vivo β-globin gene correction in autologous patient-derived hematopoietic stem and progenitor cells (HSPCs) might be an ideal treatment of SCD.

2 天之前 · β-globinopathies, comprising mainly sickle cell disease (SCD) and β-thalassemia, remain the most attractive target for gene-editing approaches, as they affect millions. SCD is caused by a point mutation in the β-globin (HBB) gene, resulting in a defective hemoglobin that polymerizes and sickles red blood cells (RBCs). β-thalassemia is caused by a mutant β-globin gene (over 200 different ...

2003年9月15日 · The term "sickle cell disease" (SCD) encompasses a group of disorders characterized by the presence of at least one hemoglobin S allele (HbS; p.Glu6Val in HBB) and a second HBB pathogenic variant resulting in abnormal hemoglobin polymerization.